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Sample records for cerebrospinal fluid biomarkers

  1. Cerebrospinal fluid biomarkers in neurological diseases in children.

    Science.gov (United States)

    Shahim, Pashtun; Månsson, Jan-Eric; Darin, Niklas; Zetterberg, Henrik; Mattsson, Niklas

    2013-01-01

    Analysis of cerebrospinal fluid (CSF) biomarkers is an integral part of neurology. Basic CSF biomarkers, such as CSF/serum albumin ratio and CSF cell counts, have been used to diagnose inflammatory and infectious CNS disorders in adults and children for decades. During recent years, however, numerous biomarkers for neuronal and astroglial injury, as well as disease-specific protein inclusions, have been developed for neurodegenerative disorders in adults. The overall aim of this paper is to give an updated overview of some of these biomarkers with special focus on their possible relevance to neurological disorders in children and adolescents.

  2. Usability of cerebrospinal fluid biomarkers in a tertiary memory clinic

    DEFF Research Database (Denmark)

    Brandt, C.; Bahl, J.C.; Heegaard, N.H.;

    2008-01-01

    AIM: Assays for cerebrospinal fluid (CSF) levels of total tau, phospho-tau protein and beta-amyloid 1-42 have been available for some years. The aim of the study was to assess the usability of these biomarkers in a mixed population of tertiary dementia referral patients in a university-based memory...... clinic. METHODS: 147 consecutive patients with a lumbar puncture as a part of their clinical workup were studied. A retrospective diagnosis was established based on consensus criteria without the knowledge of the CSF results. RESULTS: When diagnosing Alzheimer's disease (AD) compared to other diagnoses...

  3. Cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy

    Institute of Scientific and Technical Information of China (English)

    Yan-feng Li; Fang-fang Ge; Yong Zhang; Hui You; Zhen-xin Zhang

    2015-01-01

    Objective To study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer's disease. Methods Levels of amyloid proteinβ (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011. Results The levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4±265.2) ng/L, (7111.0±1033.4) ng/L, (71.8±51.5) ng/L, and 0.077±0.033, respectively in CAA dementia and (663.6±365.6) ng/L, (5115.0±2931.1) ng/L, (47.7±38.8) ng/L, and 0.192±0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (allP>0.05). Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

  4. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

    Science.gov (United States)

    Rolstad, Sindre; Berg, Anne Ingeborg; Bjerke, Maria; Johansson, Boo; Zetterberg, Henrik; Wallin, Anders

    2013-01-01

    The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. Aβ42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, Aβ42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia. PMID:23313924

  5. Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

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    Ville Leinonen

    2011-01-01

    Full Text Available The diagnosis of idiopathic normal pressure hydrocephalus (iNPH is still challenging. Alzheimer's disease (AD, along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD. A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, Aβ42, NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-α concentration was low in iNPH patients.

  6. Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson’s disease and other synucleinopathies

    OpenAIRE

    Goldstein, David S.; Holmes, Courtney; Sharabi, Yehonatan

    2012-01-01

    Central catecholamine deficiency characterizes α-synucleinopathies such as Parkinson’s disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson’s disease and two other synucleino...

  7. Longitudinal Stability of Cerebrospinal Fluid Biomarker Levels : Fulfilled Requirement for Pharmacodynamic Markers in Alzheimer's Disease

    NARCIS (Netherlands)

    Le Bastard, Nathalie; Aerts, Laetitia; Sleegers, Kristel; Martin, Jean-Jacques; Van Broeckhoven, Christine; De Deyn, Peter Paul; Engelborghs, Sebastiaan

    2013-01-01

    The current treatment for Alzheimer's disease (AD) is purely symptomatic, but medications interfering with underlying pathophysiological processes are being developed. To evaluate a possible disease-modifying effect, cerebrospinal fluid (CSF) biomarkers with a direct link to the underlying pathophys

  8. Florbetapir positron emission tomography and cerebrospinal fluid biomarkers

    Science.gov (United States)

    Hake, Ann; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Hochstetler, Helen; Witte, Michael M.; Degenhardt, Elisabeth K.; Dean, Robert A.

    2015-01-01

    Background We evaluated the relationship between florbetapir-F18 positron emission tomography (FBP PET) and cerebrospinal fluid (CSF) biomarkers. Methods Alzheimer’s Disease Neuroimaging Initiative (ADNI)-GO/2 healthy control (HC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) dementia subjects with clinical measures and CSF collected ±90 days of FBP PET data were analyzed using correlation and logistic regression. Results In HC and MCI subjects, FBP PET anterior and posterior cingulate and composite standard uptake value ratios correlated with CSF amyloid beta (Aβ1-42) and tau/Aβ1-42 ratios. Using logistic regression, Aβ1-42, total tau (t-tau), phosphorylated tau181P (p-tau), and FBP PET composite each differentiated HC versus AD. Aβ1-42 and t-tau distinguished MCI versus AD, without additional contribution by FBP PET. Total tau and p-tau added discriminative power to FBP PET when classifying HC versus AD. Conclusion Based on cross-sectional diagnostic groups, both amyloid and tau measures distinguish healthy from demented subjects. Longitudinal analyses are needed. PMID:25916563

  9. Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia

    DEFF Research Database (Denmark)

    Rostgaard, Nina; Waldemar, Gunhild; Nielsen, Jørgen Erik;

    2015-01-01

    and are important when developing new therapies. Today, the core protein biomarkers amyloid-β42, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However...

  10. Cerebrospinal Fluid Biomarkers of Simian Immunodeficiency Virus Encephalitis : CSF Biomarkers of SIV Encephalitis.

    Science.gov (United States)

    Bissel, Stephanie J; Kofler, Julia; Nyaundi, Julia; Murphey-Corb, Michael; Wisniewski, Stephen R; Wiley, Clayton A

    2016-06-01

    Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease. PMID:27059917

  11. Cerebrospinal fluid P-tau(181P) : biomarker for improved differential dementia diagnosis

    NARCIS (Netherlands)

    Struyfs, Hanne; Niemantsverdriet, Ellis; Goossens, Joery; Fransen, Erik; Martin, Jean-Jacques; De Deyn, Peter P.; Engelborghs, Sebastiaan

    2015-01-01

    The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau(181p)) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 aut

  12. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma

    OpenAIRE

    Baraniskin, Alexander; Kuhnhenn, Jan; Schlegel, Uwe; Maghnouj, Abdelouahid; Zöllner, Hannah; Schmiegel, Wolf; Hahn, Stephan; Schroers, Roland

    2011-01-01

    Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma. The objec...

  13. Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Irena Dujmovic

    2011-01-01

    Full Text Available Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested.

  14. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers

    DEFF Research Database (Denmark)

    del Campo, Marta; Mollenhauer, Brit; Bertolotto, Antonio;

    2012-01-01

    Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging...... due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting...

  15. Cognitive impairment and major depressive disorder in HIV infection and cerebrospinal fluid biomarkers

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    Sergio Monteiro de Almeida

    2013-09-01

    Full Text Available Cognitive impairment and major depressive disorder (MDD are common HIV-1 central nervous system (CNS complications. Their frequencies in AIDS patients are 36% and 45%, respectively. The diagnoses of HIV cognitive impairment are made by clinical criteria, no single laboratory test or biomarker establishes the diagnosis. Factors of indirect neuronal injury related with the pathophysiology of the HIV infection in the CNS, are the factors studied as biomarkers. In the present no biomarker is established to the diagnosis of HIV cognitive impairment, much still needs to be done. We review in this paper some biomarkers in cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive impairment. Diagnosing depression in the context of HIV can be challenging, to identify a biomarker that could help in the diagnosis would be very important, although MDD risks and neurobiology are still poorly understood.

  16. The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

    DEFF Research Database (Denmark)

    Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan;

    2011-01-01

    The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories....... The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program....

  17. Cerebrospinal fluid biomarkers for Parkinson's disease - a systematic review

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon;

    2016-01-01

    Diagnosticering af Parkinson's sygdom (PD) er baseret på den kliniske udvikling af sygdommen samt en fysisk undersøgelse af patienten, men fejldiagnosticering sker hyppigt; specielt i tidlige stadier. Biomarkører for PD kan muliggøre en tidligere og mere præcis diagnosticering samt monitorering af...

  18. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

    Science.gov (United States)

    Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin

    2016-01-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  19. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

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    Price, Richard W.; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E.; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena S.; Smith, Richard D.; Jacobs, Jon M.; Brown, Joseph N.; Gisslen, Magnus

    2013-12-13

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previouslydefined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  20. The progress of cerebrospinal fluid biomarkers in patients with neurodegenerative diseases

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    WANG Wei-zhi

    2013-02-01

    Full Text Available Neurodegenerative diseases include a heterogeneous group of diseases with complicated and overlapped clinical phenotypes. It is difficult to diagnose or identify this kind of disease due to insidious onset and chronic and progressive development. Since processes in the brain can be monitored by analysis of cerebrospinal fluid (CSF, abundant research efforts focus on the efficacy of biomarkers in CSF to indicate specific neurodegenerative lesions and to assist the diagnosis process, assessing whether one biomarker or several biomarkers together could be the reliable tools for diagnosis of specific neurodegenerative diseases. This article mainly reviews the research status and supplementary value in diagnosis and differentiation of CSF biomarkers in common degenerative diseases [e.g. multiple sclerosis (MS, Alzheimer's disease (AD, Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS].

  1. Cerebrospinal fluid biomarkers for Parkinson's disease - a systematic review

    DEFF Research Database (Denmark)

    Andersen, A D; Binzer, M; Gramsbergen, J B;

    2016-01-01

    , neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3...... a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau-proteins correlate with cognitive decline......Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments...

  2. Approach to cerebrospinal fluid (CSF) biomarker discovery and evaluation in HIV infection.

    Science.gov (United States)

    Price, Richard W; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena; Smith, Richard D; Jacobs, Jon M; Brown, Joseph N; Gisslen, Magnus

    2013-12-01

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previously-defined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  3. A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Belgium.

    Science.gov (United States)

    Somers, Charisse; Struyfs, Hanne; Goossens, Joery; Niemantsverdriet, Ellis; Luyckx, Jill; De Roeck, Naomi; De Roeck, Ellen; De Vil, Bart; Cras, Patrick; Martin, Jean-Jacques; De Deyn, Peter-Paul; Bjerke, Maria; Engelborghs, Sebastiaan

    2016-08-10

    During the past ten years, over 5,000 cerebrospinal fluid (CSF) samples were analyzed at the Reference Center for Biological Markers of Dementia (BIODEM), UAntwerp, for core Alzheimer's disease (AD) CSF biomarkers: amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: Aβ1-42 tau >296.5 pg/mL, P-tau181P >56.5 pg/mL. A CSF biomarker profile was considered to be suggestive for AD if the CSF Aβ1-42 concentration was below the cutoff, in combination with T-tau and/or P-tau181P values above the cutoff (IWG2 criteria for AD). Biomarker analyses were requested for following clinical indications: 1) neurochemical confirmation of AD in case of clinical AD, 2) neurochemical confirmation of AD in case of doubt between AD and a non-AD dementia, 3) neurochemical diagnosis of prodromal AD in case of mild cognitive impairment, 4) neurochemical confirmation of AD in case of psychiatric symptoms (like depression, psychosis), or 5) other clinical indications. During these ten years, the number of yearly referred samples increased by 238% and clinical indications for referral showed a shift from neurochemical confirmation of AD in case of clinical AD to differential dementia diagnosis in case of doubt between AD and a non-AD dementia. Four percent of the patients also had a postmortem neuropathological examination. Together, these biomarker data were the basis for several research papers, and significantly contributed to the validation of these biomarkers in autopsy-confirmed subjects. PMID:27567807

  4. Amyloid beta protein and tau in cerebrospinal fluid and plasma as biomarkers for dementia: a review of recent literature.

    NARCIS (Netherlands)

    Frankfort, S.V.; Tulner, L.R.; Campen, J.P. van; Verbeek, M.M.; Jansen, R.W.; Beijnen, J.H.

    2008-01-01

    This review addresses recent developments in amyloid beta (Abeta), total tau (t-tau), and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the protection of patients with mild cognitive impairment (MCI) into de

  5. Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid beta42.

    NARCIS (Netherlands)

    Mattsson, N.; Zegers, I.; Andreasson, U.; Bjerke, M.; Blankenstein, M.A.; Bowser, R.; Carrillo, M.C.; Gobom, J.; Heath, T.; Jenkins, R.; Jeromin, A.; Kaplow, J.; Kidd, D.; Laterza, O.F.; Lockhart, A.; Lunn, M.P.; Martone, R.L.; Mills, K.; Pannee, J.; Ratcliffe, M.; Shaw, L.M.; Simon, A.J.; Soares, H.; Teunissen, C.E.; Verbeek, M.M.; Umek, R.M.; Vanderstichele, H.; Zetterberg, H.; Blennow, K.; Portelius, E.

    2012-01-01

    Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concen

  6. Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

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    Paolo Colomba

    2014-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these.

  7. Cerebrospinal fluid proteomics and protein biomarkers in frontotemporal lobar degeneration: Current status and future perspectives.

    Science.gov (United States)

    Oeckl, Patrick; Steinacker, Petra; Feneberg, Emily; Otto, Markus

    2015-07-01

    Frontotemporal lobar degeneration (FTLD) comprises a spectrum of rare neurodegenerative diseases with an estimated prevalence of 15-22 cases per 100,000 persons including the behavioral variant of frontotemporal dementia (bvFTD), progressive non-fluent aphasia (PNFA), semantic dementia (SD), FTD with motor neuron disease (FTD-MND), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The pathogenesis of the diseases is still unclear and clinical diagnosis of FTLD is hampered by overlapping symptoms within the FTLD subtypes and with other neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Intracellular protein aggregates in the brain are a major hallmark of FTLD and implicate alterations in protein metabolism or function in the disease's pathogenesis. Cerebrospinal fluid (CSF) which surrounds the brain can be used to study changes in neurodegenerative diseases and to identify disease-related mechanisms or neurochemical biomarkers for diagnosis. In the present review, we will give an overview of the current literature on proteomic studies in CSF of FTLD patients. Reports of targeted and unbiased proteomic approaches are included and the results are discussed in regard of their informative value about disease pathology and the suitability to be used as diagnostic biomarkers. Finally, we will give some future perspectives on CSF proteomics and a list of candidate biomarkers which might be interesting for validation in further studies. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.

  8. Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer's disease.

    Science.gov (United States)

    Irwin, David J; Trojanowski, John Q; Grossman, Murray

    2013-01-01

    Accurate ante mortem diagnosis in frontotemporal lobar degeneration (FTLD) is crucial to the development and implementation of etiology-based therapies. Several neurodegenerative disease-associated proteins, including the major protein constituents of inclusions in Alzheimer's disease (AD) associated with amyloid-beta (Aβ(1-42)) plaque and tau neurofibrillary tangle pathology, can be measured in cerebrospinal fluid (CSF) for diagnostic applications. Comparative studies using autopsy-confirmed samples suggest that CSF total-tau (t-tau) and Aβ(1-42) levels can accurately distinguish FTLD from AD, with a high t-tau to Aβ(1-42) ratio diagnostic of AD; however, there is also an urgent need for FTLD-specific biomarkers. These analytes will require validation in large autopsy-confirmed cohorts and face challenges of standardization of within- and between-laboratory sources of error. In addition, CSF biomarkers with prognostic utility and longitudinal study of CSF biomarker levels over the course of disease are also needed. Current goals in the field include identification of analytes that are easily and reliably measured and can be used alone or in a multi-modal approach to provide an accurate prediction of underlying neuropathology for use in clinical trials of disease modifying treatments in FTLD. To achieve these goals it will be of the utmost importance to view neurodegenerative disease, including FTLD, as a clinicopathological entity, rather than exclusively a clinical syndrome.

  9. Cerebrospinal Fluid Biomarkers for Differentiation of Frontotemporal Lobar Degeneration from Alzheimer’s Disease

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    David J Irwin

    2013-02-01

    Full Text Available Accurate ante mortem diagnosis in frontotemporal lobar degeneration (FTLD is crucial to the development and implementation of etiology-based therapies. Several neurodegenerative disease-associated proteins, including the major protein constituents of inclusions in Alzheimer’s disease (AD associated with amyloid-beta (Aβ1-42 plaque and tau neurofibrillary tangle pathology, can be measured in cerebrospinal fluid (CSF for diagnostic applications. Comparative studies using autopsy-confirmed samples suggest that CSF total-tau (t-tau and Aβ1-42 levels can accurately distinguish FTLD from AD, with a high t-tau to Aβ1-42 ratio diagnostic of AD; however, there is also an urgent need for FTLD-specific biomarkers. These analytes will require validation in large autopsy-confirmed cohorts and face challenges of standardization of within- and between-laboratory sources of error. In addition, CSF biomarkers with prognostic utility and longitudinal study of CSF biomarker levels over the course of disease are also needed. Current goals in the field include identification of analytes that are easily and reliably measured and can be used alone or in a multi-modal approach to provide an accurate prediction of underlying neuropathology for use in clinical trials of disease modifying treatments in FTLD. To achieve these goals it will be of the utmost importance to view neurodegenerative disease, including FTLD, as a clinicopathological entity, rather than exclusively a clinical syndrome.

  10. The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid and correlates to dementia-related biomarkers tau proteins and amyloid-beta

    DEFF Research Database (Denmark)

    Abuyaman, Omar; Nexo, Ebba

    2015-01-01

    in cerebrospinal fluid (CSF) and show its correlations to dementia-related biomarkers tau proteins and amyloid-beta. METHODS: We collected 223 cerebrospinal fluid samples and corresponding plasma samples (n = 46). We measured CSF and plasma sCD320, holoTC and total TC employing in-house ELISA methods and CSF...

  11. Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma.

    Science.gov (United States)

    Strehlow, Felicitas; Bauer, Sandra; Martus, Peter; Weller, Michael; Roth, Patrick; Schlegel, Uwe; Seidel, Sabine; Scheibenbogen, Carmen; Korfel, Agnieszka; Kreher, Stephan

    2016-08-01

    Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL. OPN concentrations in CSF from 37 patients with CNSL (29 with primary CNSL and 8 with secondary CNS involvement of systemic lymphoma) and 36 controls [6 patients with inflammatory CNS disease other than multiple sclerosis (MS), 8 with MS, 9 with glioblastoma (GBM) and 13 healthy controls] were determined using an enzyme-linked immunosorbent assay. Non-parametric tests and receiver operating characteristic (ROC) curves were performed for determination of diagnostic accuracy. Median CSF OPN level in all CNSL patients was 620 ng/mL and higher than in patients with inflammatory CNS disease (356 ng/mL); P curve was 0.865 [95 % confidence interval (CI) 0.745-0.985] for differentiating CNSL and patients with inflammatory CNS disease; 0.956 (95 % CI 0.898-1.000) for CNSL and MS patients; 0.988 (95 % CI 0.964-1.000) for CNSL and GBM patients, and 0.915 (95 % CI 0.834-0.996) for CNSL patients and healthy controls. In multivariate analysis, high CSF OPN level was associated with shorter progression-free (HR 1.61, 95 % CI 1.13-2.31; P = .009) and overall survival (HR 1.52, 95 % CI 1.04-2.21; P = .029). CSF OPN is a potential biomarker in CNSL. PMID:27294357

  12. Peptide fingerprinting of Alzheimer's disease in cerebrospinal fluid: identification and prospective evaluation of new synaptic biomarkers.

    Directory of Open Access Journals (Sweden)

    Holger Jahn

    Full Text Available BACKGROUND: Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier in the disease process to avoid disability requiring new diagnostic tools. The objective of this study is to develop a new method for the differential diagnosis and identification of new biomarkers of Alzheimer's disease (AD using capillary-electrophoresis coupled to mass-spectrometry (CE-MS and to assess the potential of early diagnosis of AD. METHODS AND FINDINGS: Cerebrospinal fluid (CSF of 159 out-patients of a memory-clinic at a University Hospital suffering from neurodegenerative disorders and 17 cognitively-healthy controls was used to create differential peptide pattern for dementias and prospective blinded-comparison of sensitivity and specificity for AD diagnosis against the Criterion standard in a naturalistic prospective sample of patients. Sensitivity and specificity of the new method compared to standard diagnostic procedures and identification of new putative biomarkers for AD was the main outcome measure. CE-MS was used to reliably detect 1104 low-molecular-weight peptides in CSF. Training-sets of patients with clinically secured sporadic Alzheimer's disease, frontotemporal dementia, and cognitively healthy controls allowed establishing discriminative biomarker pattern for diagnosis of AD. This pattern was already detectable in patients with mild cognitive impairment (MCI. The AD-pattern was tested in a prospective sample of patients (n = 100 and AD was diagnosed with a sensitivity of 87% and a specificity of 83%. Using CSF measurements of beta-amyloid1-42, total-tau, and phospho(181-tau, AD-diagnosis had a sensitivity of 88% and a specificity of 67% in the same sample. Sequence analysis of the discriminating biomarkers identified fragments of synaptic proteins like proSAAS, apolipoprotein J, neurosecretory protein VGF, phospholemman, and chromogranin A. CONCLUSIONS: The method may allow early differential

  13. Cognitive Performance and Cerebrospinal Fluid Biomarkers of Neurodegeneration: A Study of Patients with Bipolar Disorder and Healthy Controls

    OpenAIRE

    Sindre Rolstad; Joel Jakobsson; Carl Sellgren; Carl-Johan Ekman; Kaj Blennow; Henrik Zetterberg; Erik Pålsson; Mikael Landén

    2015-01-01

    The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (Aβ)1-42, ratios of Aβ42/40 and Aβ42/38, soluble amyloid precursor protein α and β, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 hea...

  14. Cytoskeletal proteins in the cerebrospinal fluid as biomarker of multiple sclerosis.

    Science.gov (United States)

    Madeddu, Roberto; Farace, Cristiano; Tolu, Paola; Solinas, Giuliana; Asara, Yolande; Sotgiu, Maria Alessandra; Delogu, Lucia Gemma; Prados, Jose Carlos; Sotgiu, Stefano; Montella, Andrea

    2013-02-01

    The axonal cytoskeleton is a finely organized system, essential for maintaining the integrity of the axon. Axonal degeneration is implicated in the pathogenesis of unremitting disability of multiple sclerosis (MS). Purpose of this study is to evaluate levels of cytoskeletal proteins such as neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), and β-tubulin (β-Tub) isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their correlation with MS clinical indices. CSF levels of cytoskeletal proteins were determined in 51 patients: 33 with MS and 18 with other neurological diseases (OND). NFL, GFAP and β-Tub II proteins were significantly higher (p 0.05) was found between MS and OND with regard to β-Tub III. Interestingly, levels of β-Tub III and NFL were higher in progressive than in remitting MS forms; on the contrary, higher levels of β-Tub II and GFAP were found in remitting MS forms. However, with the exception of β-Tub III, all proteins tend to decrease their CSF levels concomitantly with the increasing disability (EDSS) score. Overall, our results might indicate β-Tub II as a potential candidate for diagnostic and β-Tub III as a possible prognostic biomarker of MS. Therefore, further analyses are legitimated and desirable. PMID:22362332

  15. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children

    Directory of Open Access Journals (Sweden)

    Wiredu Edwin K

    2007-11-01

    Full Text Available Abstract Background Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM, a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. Methods Postmortem serum and cerebrospinal fluid (CSF samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA, and non-malarial (NM causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70, IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF, MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC, Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55, sTNF-R2 (p75, MMP-9, TGF-β1, PDGF bb and VEGF were measured and the results compared between the 3 groups. Results After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2 were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. Conclusion The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting

  16. Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Okko T Pyykkö

    Full Text Available BACKGROUND: The significance of amyloid precursor protein (APP and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH and Alzheimer's disease (AD is unknown. OBJECTIVE: To investigate the role of soluble APP (sAPP and amyloid beta (Aβ isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ findings. METHODS: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders, 26 AD (10 mixed iNPH+AD, and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau, non-AD-related Aβ isoforms (Aβ38, Aβ40, sAPP isoforms (sAPPα, sAPPβ, proinflammatory cytokines (several interleukins (IL, interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha and biomarkers of neuronal damage (neurofilament light and myelin basic protein were measured. All patients were genotyped for APOE. RESULTS: Lumbar CSF levels of sAPPα were lower (p<0.05 in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06. CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = -0.295, p = 0.003 and lumbar (r = -0.356, p = 0.01 samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001 were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure

  17. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease.

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    Richard J Perrin

    Full Text Available Ideally, disease modifying therapies for Alzheimer disease (AD will be applied during the 'preclinical' stage (pathology present with cognition intact before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1 (n = 24 and cognitively normal controls (CDR 0 (n = 24 were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA. Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs to a larger independent cohort (n = 292 that included individuals with very mild dementia (CDR 0.5. Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI] and 0.88 (0.81-0.94 CI, respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding

  18. Biomarker discovery in human cerebrospinal fluid: The need for integrative metabolome and proteome databases

    NARCIS (Netherlands)

    E. Schwarz (Emanuel); F.E. Torrey; P.C. Guest (Paul); S. Bahn (Sabine)

    2012-01-01

    textabstractThe number of metabolites identified in human cerebrospinal fluid (CSF) has steadily increased over the past 5 years, and in this issue of Genome Medicine David Wishart and colleagues provide a comprehensive update that brings the number of metabolites listed in the CSF metabolome databa

  19. Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease

    DEFF Research Database (Denmark)

    Simonsen, A.H.; McGuire, J.; Podust, V.N.;

    2008-01-01

    An early and accurate diagnosis of Alzheimer's disease (AD) is required to initiate symptomatic treatment with currently approved drugs and will be of even greater importance if disease modifying compounds in development display a clinical effect. Protein profiles of human cerebrospinal fluid...

  20. Cerebrospinal fluid P-tau181P: biomarker for improved differential dementia diagnosis

    Directory of Open Access Journals (Sweden)

    Hanne eStruyfs

    2015-06-01

    Full Text Available The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P in the Alzheimer’s disease (AD cerebrospinal fluid (CSF biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients.The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of Aβ1-42, T-tau, and P-tau181P were determined with single analyte ELISA-kits (INNOTEST®, Fujirebio, Ghent, Belgium. Diagnostic accuracy was assessed through receiver operating characteristic (ROC curve analyses to obtain area under the curve (AUC values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests.The Aβ1-42/P-tau181P ratio (AUC=0.770 performed significantly better than Aβ1-42 (AUC=0.677, P=0.004, T-tau (AUC=0.592, P<0.001, and Aβ1-42/T-tau (AUC=0.678, P=0.001, while P-tau181P (AUC=0.720 performed significantly better than T-tau (AUC=0.592, P<0.001 to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, Aβ1-42/P-tau181P (AUC=0.894 discriminated AD from frontotemporal dementia significantly better than Aβ1-42 (AUC=0.776, P=0.020 and T-tau (AUC=0.746, P=0.004, while P-tau181P/T-tau (AUC=0.958 significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to Aβ1-42 (AUC=0.688, P=0.004, T-tau (AUC=0.874, P=0.040, and Aβ1-42/P-tau181P (AUC=0.760, P=0.003.In conclusion, this study demonstrates P-tau181P is an essential component of the AD CSF biomarker panel and combined assessment of Aβ1-42, T-tau, and P-tau181P renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias.

  1. Cerebrospinal Fluid P-Tau181P: Biomarker for Improved Differential Dementia Diagnosis.

    Science.gov (United States)

    Struyfs, Hanne; Niemantsverdriet, Ellis; Goossens, Joery; Fransen, Erik; Martin, Jean-Jacques; De Deyn, Peter P; Engelborghs, Sebastiaan

    2015-01-01

    The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and P-tau181P were determined with single analyte ELISA-kits (INNOTEST(®), Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The Aβ1-42/P-tau181P ratio (AUC = 0.770) performed significantly better than Aβ1-42 (AUC = 0.677, P = 0.004), T-tau (AUC = 0.592, P < 0.001), and Aβ1-42/T-tau (AUC = 0.678, P = 0.001), while P-tau181P (AUC = 0.720) performed significantly better than T-tau (AUC = 0.592, P < 0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, Aβ1-42/P-tau181P (AUC = 0.894) discriminated AD from frontotemporal dementia significantly better than Aβ1-42 (AUC = 0.776, P = 0.020) and T-tau (AUC = 0.746, P = 0.004), while P-tau181P/T-tau (AUC = 0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to Aβ1-42 (AUC = 0.688, P = 0.004), T-tau (AUC = 0.874, P = 0.040), and Aβ1-42/P-tau181P (AUC = 0.760, P = 0.003). In conclusion, this study demonstrates P-tau181P is an essential component of the AD CSF biomarker

  2. Chemokine biomarkers in central nervous system tissue and cerebrospinal fluid in the Theiler's virus model mirror those in multiple sclerosis.

    Science.gov (United States)

    Pachner, Andrew R; Li, Libin; Gilli, Francesca

    2015-12-01

    Chemokines have increasingly been implicated in inflammatory and infectious disease of the central nervous system, both as biomarkers and as molecules important in pathogenesis. Multiple sclerosis is a disabling disease of unknown etiology, and recently chemokines have been identified as being upregulated molecules in the disease. We were interested in how the chemokine expression patterns in the central nervous system of a viral model of multiple sclerosis, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), compared to that in humans with multiple sclerosis. Cerebrospinal fluid and spinal cord tissue were analyzed for expression of a range of cytokines and chemokines. Three chemokines, CXCL10, CXCL9, and CCL5 were strongly and specifically upregulated in both the cerebrospinal fluid and spinal cord in chronic disease, a pattern identical to that in multiple sclerosis. These data, the first study of cytokines in central nervous system tissue and cerebrospinal fluid in TMEV-IDD, support the hypothesis that multiple sclerosis is caused by chronic infection with an as-yet unidentified pathogen, possibly a picornavirus.

  3. Conventional cerebrospinal fluid scanning

    Energy Technology Data Exchange (ETDEWEB)

    Schicha, H.

    1985-06-01

    Conventional cerebrospinal fluid scanning (CSF scanning) today is mainly carried out in addition to computerized tomography to obtain information about liquor flow kinetics. Especially in patients with communicating obstructive hydrocephalus, CSF scanning is clinically useful for the decision for shunt surgery. In patients with intracranial cysts, CSF scanning can provide information about liquor circulation. Further indications for CSF scanning include the assessment of shunt patency especially in children, as well as the detection and localization of cerebrospinal fluid leaks.

  4. Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation.

    Directory of Open Access Journals (Sweden)

    Bibiana Bielekova

    Full Text Available Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF derived from 16 untreated patients with highly active multiple sclerosis (MS we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72 and a confirmatory cohort (n = 167 of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC curve analysis in conjunction with principal component analysis (PCA, which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND in comparison to non-inflammatory neurological disorder patients (NIND at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924.Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically

  5. Cognitive performance and cerebrospinal fluid biomarkers of neurodegeneration: a study of patients with bipolar disorder and healthy controls.

    Directory of Open Access Journals (Sweden)

    Sindre Rolstad

    Full Text Available The purpose of the present study was to investigate if cerebrospinal fluid (CSF biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (Aβ1-42, ratios of Aβ42/40 and Aβ42/38, soluble amyloid precursor protein α and β, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers. In patients, the CSF biomarkers explained a significant proportion of the variance (15-36%, p=.002 - <.0005 in all cognitive domains independently of age, medication, disease status, and bipolar subtype I or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain changes, i.e., P-tau and Aβ1-42, did not contribute significantly. In healthy controls, CSF biomarkers did not explain the variance in cognitive performance. Selected CSF biomarkers of neurodegenerative processes accounted for cognitive performance in persons with bipolar disorder, but not for healthy controls. Specifically, the ratios of Aβ42/40 and Aβ42/38 were consistently associated with altered cognitive performance.

  6. Cognitive performance and cerebrospinal fluid biomarkers of neurodegeneration: a study of patients with bipolar disorder and healthy controls.

    Science.gov (United States)

    Rolstad, Sindre; Jakobsson, Joel; Sellgren, Carl; Ekman, Carl-Johan; Blennow, Kaj; Zetterberg, Henrik; Pålsson, Erik; Landén, Mikael

    2015-01-01

    The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (Aβ)1-42, ratios of Aβ42/40 and Aβ42/38, soluble amyloid precursor protein α and β, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers. In patients, the CSF biomarkers explained a significant proportion of the variance (15-36%, p=.002 - bipolar subtype I or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain changes, i.e., P-tau and Aβ1-42, did not contribute significantly. In healthy controls, CSF biomarkers did not explain the variance in cognitive performance. Selected CSF biomarkers of neurodegenerative processes accounted for cognitive performance in persons with bipolar disorder, but not for healthy controls. Specifically, the ratios of Aβ42/40 and Aβ42/38 were consistently associated with altered cognitive performance. PMID:25954806

  7. Protein profiling of cerebrospinal fluid

    DEFF Research Database (Denmark)

    Simonsen, Anja H

    2012-01-01

    The cerebrospinal fluid (CSF) perfuses the brain and spinal cord. CSF contains proteins and peptides important for brain physiology and potentially also relevant for brain pathology. Hence, CSF is the perfect source to search for new biomarkers to improve diagnosis of neurological diseases as well...... as to monitor the performance of disease-modifying drugs. This chapter presents methods for SELDI-TOF profiling of CSF as well as useful advice regarding pre-analytical factors to be considered....

  8. Cerebrospinal fluid leak (image)

    Science.gov (United States)

    ... and spinal cord. It protects the brain and spinal cord by acting like a liquid cushion. The fluid allows the organs to be buoyant protecting them from blows or other trauma. Inside the skull the cerebrospinal fluid is contained by the dura ...

  9. Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

    Science.gov (United States)

    Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

    2016-01-01

    Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

  10. Investigation of autoantibody profiles for cerebrospinal fluid biomarker discovery in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Beyer, Natascha Helena; Lueking, Angelika; Kowald, Axel;

    2012-01-01

    Using the UNIarray® marker technology platform, cerebrospinal fluid immunoglobulin G reactivities of 15 controls and 17 RRMS patients against human recombinant proteins were investigated. Patient cerebrospinal fluids were oligoclonal band positive and reactivities were compared to that of sex...

  11. Nerve growth factor expression in astrocytoma and cerebrospinal fluid: a new biomarker for prognosis of astrocytoma

    Institute of Scientific and Technical Information of China (English)

    LI Qiao-yu; FENG Yun; XU Wen-lin; YANG Yong; ZHANG Yan; ZHANG Zhi-jian; GONG Ai-hua; YUAN Zhi-cheng; LU Pei-song; ZHAN Li-ping; WANG Peng

    2011-01-01

    Background Recent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance.Methods Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control.Results NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades Ⅲ-Ⅳ astrocytomas (70.0%) was higher than that of grades Ⅰ-Ⅱ astrocytoma (28.6%, P<0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r=0.755, P<0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade Ⅰ-Ⅱ patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade Ⅰ-Ⅱ patients (P<0.05). In astrocytoma Ⅲ-Ⅳ patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P<0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased.Conclusions NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients.Because of the easy

  12. RHABDOMYOBLASTS IN CEREBROSPINAL FLUID

    OpenAIRE

    Deepak Nayak; Sushma V

    2013-01-01

    Rhabdomyosarcoma (RMS) is an aggressive soft tissue malignancy, not uncommonly seen in adults. The location of this malignancy is quite ubiquitous. However, a parameningeal location is uncommon and accounts for about 16% of all rhabdomyosarcomas. We report an instance where rhabdomyoblasts were seen infiltrati ng the cerebrospinal fluid (CSF). A 35 year old female patient presented to our hospita l with the primary complaints of bilateral nose block and left side...

  13. The proteomic toolbox for studying cerebrospinal fluid

    NARCIS (Netherlands)

    Gool, A.J. van; Hendrickson, R.C.

    2012-01-01

    Cerebrospinal fluid (CSF) can be considered the most promising biosample for the discovery and analysis of biomarkers in neuroscience, an area of great medical need. CSF is a body fluid that surrounds the brain and provides a rich pool of biochemical markers, both proteomic and metabolomic, that ref

  14. Relationship between cerebrospinal fluid biomarkers for inflammation, demyelination and neurodegeneration in acute optic neuritis

    DEFF Research Database (Denmark)

    Modvig, Signe; Degn, Matilda; Horwitz, Henrik;

    2013-01-01

    Various inflammatory biomarkers show prognostic potential for multiple sclerosis (MS)-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of the...

  15. MGMT promoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma

    Science.gov (United States)

    WANG, ZHENG; JIANG, WEI; WANG, YAHONG; GUO, YANG; CONG, ZHENG; DU, FANGFANG; SONG, BIN

    2015-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a conventional technique to predict the prognosis or individualized treatment of glioma in tumor tissue following surgery or biopsy. However, the technique cannot be applied in those glioma patients with concomitant neurological dysfunctions or advanced age. The present study aimed to find a new minimally invasive and efficient alternative method for the detection of MGMT promoter methylation. The expression of MGMT promoter methylation was assessed in peripheral blood and cerebrospinal fluid (CSF), and compared to the corresponding tumor tissue from glioma patients. The 89 patients in the study [32 World Health Organization (WHO) grade II, 19 WHO grade III and 38 WHO grade IV) were pathologically-diagnosed glioma and received radiation therapy following sample collection. The resected glioma tumor tissue (89), corresponding serum (89) and CSF (78) samples were collected for the detection of MGMT promoter methylation using methylation-specific polymerase chain reaction. The sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum were compared. Among the tumor tissue samples, 51/89 (57.3%) showed MGMT promoter methylation. The specificity of the detection in the CSF and serum samples reached 100%. The sensitivity of MGMT promoter methylation detection in CSF and serum were 26/40 (65.0%) and 19/51 (37.3%), respectively (P<0.05). In the WHO II, III and IV subgroups, the sensitivities of MGMT promoter methylation detection using CSF were 8/12 (66.7%), 11/18 (61.1%) and 7/10 (70.0%), respectively, which were significantly higher than the sensitivities using serum (7/21, 33.3%; 7/19, 36.8%; and 5/11, 45.5%, respectively P<0.05). Among patients with residual postoperative tumors, the sensitivities of detecting MGMT promoter methylation using CSF and serum were 18/25 (72.0%) and 10/24 (41.7%), respectively, both of which were significantly higher than the corresponding values

  16. Cerebrospinal fluid biomarkers for Alzheimer’s disease: the role of apolipoprotein E genotype, age, and sex

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    Mehrabian S

    2015-12-01

    Full Text Available Shima Mehrabian,1 Panagiotis Alexopoulos,2,3 Marion Ortner,2 Latchezar Traykov,1 Timo Grimmer,2 Alexander Kurz,2 Hans Förstl,2 Horst Bickel,2 Janine Diehl-Schmid21Department of Neurology, University Hospital “Alexandrovska”, Sofia, Bulgaria; 2Department of Psychiatry, Technische Universität München, Munich, Germany; 3Department of Psychiatry, University of Patras, Patras, GreeceIntroduction: Cerebrospinal fluid (CSF biomarkers improve the diagnostic accuracy for Alzheimer’s disease (AD, even at the predementia stage of the disease. The ε4-allele of apolipoprotein E (ApoE ε4, female sex, and older age are well-known risk factors for AD. It is unclear how these risk factors affect the CSF biomarkers in patients with AD.Aim: The objective of this study was to investigate the associations of ApoE ε4, sex, and age with CSF biomarker levels in a unicenter sample of patients with AD that includes a high proportion of patients with early-onset AD (EOAD.Methods: The CSF levels of amyloid-β 1-42 (Aβ1-42 and total-tau of 117 subjects with mild to moderate AD (55 late-onset AD and 62 EOAD were assessed. All subjects underwent ApoE genotyping, clinical evaluation, comprehensive neuropsychological assessments, and neuroimaging. Associations between CSF biomarker levels, ApoE ε4 allele frequency, age, and sex were evaluated.Results: In the whole patient sample and in the late-onset AD subgroup ε4 homozygous subjects had significantly lower CSF Aβ1-42 levels compared with ε4 heterozygous subjects and ε4 noncarriers. This association was not detected in the EOAD group. Age group, sex, and severity of cognitive decline did not have a significant impact on CSF Aβ1-42 levels. No significant associations were found between ApoE ε4 allele frequency and CSF total-tau levels.Conclusion: ApoE ε4 allele is associated with a reduction of CSF Aβ1-42 levels. This result is consistent with the findings of several previous studies. In the subgroup of

  17. Cerebrospinal Fluid Calbindin D Concentration as a Biomarker of Cerebellar Disease Progression in Niemann-Pick Type C1 Disease

    Science.gov (United States)

    Bagel, Jessica; Sampson, Maureen; Farhat, Nicole; Ding, Wenge; Swain, Gary; Prociuk, Maria; O’Donnell, Patricia; Drobatz, Kenneth; Gurda, Brittney; Wassif, Christopher; Remaley, Alan; Porter, Forbes; Vite, Charles

    2016-01-01

    Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear evidence of the therapeutic efficacy of 2-hydroxypropyl-β-cyclodextrin (HPβCD) in animal models resulted in the initiation of a phase I/IIa clinical trial in 2013 and a phase IIb/III trial in 2015. With clinical trials ongoing, validation of a biomarker to track disease progression and serve as a supporting outcome measure of therapeutic efficacy has become compulsory. In this study, we evaluated calcium-binding protein calbindin D-28K (calbindin) concentrations in the cerebrospinal fluid (CSF) as a biomarker of NPC1 disease. In the naturally occurring feline model, CSF calbindin was significantly elevated at 3 weeks of age, prior to the onset of cerebellar dysfunction, and steadily increased to >10-fold over normal at end-stage disease. Biweekly intrathecal administration of HPβCD initiated prior to the onset of neurologic dysfunction completely normalized CSF calbindin in NPC1 cats at all time points analyzed when followed up to 78 weeks of age. Initiation of HPβCD after the onset of clinical signs (16 weeks of age) resulted in a delayed reduction of calbindin levels in the CSF. Evaluation of CSF from patients with NPC1 revealed that calbindin concentrations were significantly elevated compared with CSF samples collected from unaffected patients. Off-label treatment of patients with NPC1 with miglustat, an inhibitor of glycosphingolipid biosynthesis, significantly decreased CSF calbindin compared with pretreatment concentrations. These data suggest that the CSF calbindin concentration is a sensitive biomarker of NPC1 disease that could be instrumental as an outcome measure of therapeutic efficacy in ongoing clinical trials. PMID:27307499

  18. RHABDOMYOBLASTS IN CEREBROSPINAL FLUID

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    Deepak Nayak

    2013-01-01

    Full Text Available Rhabdomyosarcoma (RMS is an aggressive soft tissue malignancy, not uncommonly seen in adults. The location of this malignancy is quite ubiquitous. However, a parameningeal location is uncommon and accounts for about 16% of all rhabdomyosarcomas. We report an instance where rhabdomyoblasts were seen infiltrati ng the cerebrospinal fluid (CSF. A 35 year old female patient presented to our hospita l with the primary complaints of bilateral nose block and left sided headache since1 month. Clinically, a deviated nasal septum was diagnosed which needed a septal surgery. Since t he hematological parameters showed a pancytopenia, the surgery was postponed. The patient pr esented 3 weeks later with additional complaints of worsening headache and significant blu rring of vision in her left eye. The MRI scan revealed a midline, dural-based mass. A therape utic tap of the cerebrospinal fluid sent to the clinical laboratory for analysis which showed l arge abnormal cells (figure 1. The bone marrow also showed similar cells, with karyomegaly, dense chromatin, and coalescing vacuoles which were Periodic Acid Schiff (PAS negative. The biopsy from the mass was diagnosed as rhabdomyosarcoma (parameningeal type. Immunohistoc hemistry showed positivity for Myogenin and Myo-D1.

  19. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.

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    Mohsen Khademi

    Full Text Available Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS. The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066 using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9, chemokine (C-X-C motif ligand 13 (CXCL13, osteopontin (OPN and neurofilament-light chain (NFL were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive, clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later

  20. Relationship between cerebrospinal fluid biomarkers for inflammation, demyelination and neurodegeneration in acute optic neuritis.

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    Signe Modvig

    Full Text Available BACKGROUND: Various inflammatory biomarkers show prognostic potential for multiple sclerosis (MS-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of these relationships could aid the appropriate implementation of prognostic biomarkers in clinical practice. OBJECTIVE: To investigate the interrelation between biomarkers of inflammation, demyelination and neurodegeneration in acute optic neuritis and to assess their association to measures of MS risk. MATERIAL AND METHODS: A prospective study at a tertiary referral centre from June 2011 to December 2012 of 56 patients with optic neuritis as a first demyelinating symptom and 27 healthy volunteers. Lumbar puncture was performed within 28 (median 16 days of onset. CSF levels of CXCL13, matrix metalloproteinase (MMP-9, CXCL10, CCL-2, osteopontin and chitinase-3-like-1, myelin basic protein (MBP and neurofilament light-chain (NF-L were determined. MS-risk outcome measures were dissemination in space (DIS of white matter lesions on cerebral MRI, CSF oligoclonal bands and elevated IgG-index. RESULTS: IN THE INTERRELATION ANALYSIS THE BIOMARKERS SHOWED CLOSE CORRELATIONS WITHIN TWO DISTINCT GROUPS: Biomarkers of leukocyte infiltration (CXCL13, MMP-9 and CXCL10 were strongly associated (p<0.0001 for all. Osteopontin and chitinase-3-like-1 were also tightly associated (p<0.0001 and correlated strongly to tissue damage markers (NF-L and MBP. The biomarkers of leukocyte infiltration all associated strongly with MS-risk parameters, whereas CHI3L1 and MBP correlated with MRI DIS, but not with CSF MS-risk parameters and osteopontin and NF-L did not correlate with any MS-risk parameters. CONCLUSIONS: OUR FINDINGS SUGGEST TWO DISTINCT INFLAMMATORY PROCESSES: one of leukocyte infiltration, represented by CXCL13, CXCL10 and MMP-9, strongly associated with and

  1. Peptide Fingerprinting of Alzheimer's Disease in Cerebrospinal Fluid: Identification and Prospective Evaluation of New Synaptic Biomarkers

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    Holger Jahn; Stefan Wittke; Petra Zürbig; Raedler, Thomas J; Sönke Arlt; Markus Kellmann; William Mullen; Martin Eichenlaub; Harald Mischak; Klaus Wiedemann

    2011-01-01

    Background: Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier in the disease process to avoid disability requiring new diagnostic tools. The objective of this study is to develop a new method for the differential diagnosis and identification of new biomarkers of Alzheimer's disease (AD) using capillary-electrophoresis coupled to mass-spectrometry (CE-MS) and to assess the potential of early diagnosis of AD. Methods and Findings: Cerebro...

  2. Cerebrospinal Fluid Inflammatory Biomarkers Reflect Clinical Severity in Huntington’s Disease

    Science.gov (United States)

    Byrne, Lauren M.; McColgan, Peter; Robertson, Nicola; Tabrizi, Sarah J.; Zetterberg, Henrik; Wild, Edward J.

    2016-01-01

    Introduction Immune system activation is involved in Huntington’s disease (HD) pathogenesis and biomarkers for this process could be relevant to study the disease and characterise the therapeutic response to specific interventions. We aimed to study inflammatory cytokines and microglial markers in the CSF of HD patients. Methods CSF TNF-α, IL-1β, IL-6, IL-8, YKL-40, chitotriosidase, total tau and neurofilament light chain (NFL) from 23 mutation carriers and 14 healthy controls were assayed. Results CSF TNF-α and IL-1β were below the limit of detection. Mutation carriers had higher YKL-40 (p = 0.003), chitotriosidase (p = 0.015) and IL-6 (p = 0.041) than controls. YKL-40 significantly correlated with disease stage (p = 0.007), UHDRS total functional capacity score (r = -0.46, p = 0.016), and UHDRS total motor score (r = 0.59, p = 4.5*10−4) after adjustment for age. Conclusion YKL-40 levels in CSF may, after further study, come to have a role as biomarkers for some aspects of HD. Further investigation is needed to support our exploratory findings. PMID:27657730

  3. Association between NME8 locus polymorphism and cognitive decline, cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease.

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    Ying Liu

    Full Text Available Recently, a large meta-analysis of five genome wide association studies (GWAS identified a novel locus (rs2718058 adjacent to NME8 that played a preventive role in Alzheimer's disease (AD. However, this link between the single nucleotide polymorphism (SNP rs2718058 and the pathology of AD have not been mentioned yet. Therefore, this study assessed the strength of association between the NME8 rs2718058 genotypes and AD-related measures including the cerebrospinal fluid (CSF amyloid beta, tau, P-tau concentrations, neuroimaging biomarkers and cognitive performance, in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI database. We used information of a total of 719 individuals, including 211 normal cognition (NC, 346 mild cognitive impairment (MCI and 162 AD. Although we didn't observe a positive relationship between rs2718058 and AD, it was significantly associated with several AD related endophenotypes. Among the normal cognitively normal participants, the minor allele G carriers showed significantly associated with higher CDRSB score than A allele carriers (P = 0.021. Occipital gyrus atrophy were significantly associated with NME8 genotype status (P = 0.002, with A allele carriers has more atrophy than the minor allele G carriers in AD patients; lateral ventricle (both right and left cerebral metabolic rate for glucose (CMRgl were significantly associated with NME8 genotype (P < 0.05, with GA genotype had higher metabolism than GG and AA genotypes in MCI group; the atrophic right hippocampus in 18 months is significantly different between the three group, with GG and AA genotypes had more hippocampus atrophy than GA genotypes in the whole group. Together, our results are consistent with the direction of previous research, suggesting that NME8 rs2718058 appears to play a role in lowering the brain neurodegeneration.

  4. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

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    Chaojun Hu

    Full Text Available Autoantibodies in cerebrospinal fluid (CSF from patients with neuropsychiatric systemic lupus erythematosus (NPSLE may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosuspatients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43.Anti-proliferating cell nuclear antigen (PCNA was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A. The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045.Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009. Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

  5. Cardiac biomarkers in blood, and pericardial and cerebrospinal fluids of forensic autopsy cases: A reassessment with special regard to postmortem interval.

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    Chen, Jian-Hua; Inamori-Kawamoto, Osamu; Michiue, Tomomi; Ikeda, Sayuko; Ishikawa, Takaki; Maeda, Hitoshi

    2015-09-01

    Previous studies suggested possible application of postmortem biochemistry of myocardial biomarkers to the investigation of sudden cardiac death; however, differences from clinical findings should be considered in autopsy materials. The present study involved a comprehensive investigation of cardiac troponin T and I (cTnT and cTnI), and creatine kinase MB (CK-MB) in cardiac and peripheral external iliac venous blood, pericardial fluid (PCF) and cerebrospinal fluid (CSF) for reassessment, with special regard to the estimated postmortem interval in relation to the cause of death, reviewing a large number of forensic autopsy cases (n=1923). These cardiac biomarkers showed cause-of-death- and postmortem-time-dependent differences: blood and PCF levels of each marker were higher in hyperthermia (heatstroke), bathwater drowning and chronic congestive heart disease in cases of postmortem interval (PMI) PMI of <48h. CSF cTnI and CK-MB showed similar findings. There was no difference between myocardial infarction and other causes of death to be discriminated, including asphyxiation, drowning and fire fatality. These findings are similar to clinical observations in critical ill patients, suggesting that elevated cardiac biomarkers cannot be a specific finding for death from acute ischemic heart disease, but indicate the severity of myocardial injury in postmortem investigation. PMID:26052007

  6. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

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    Todd D. Levine

    2012-01-01

    Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

  7. Impact of the 2008-2012 French Alzheimer Plan on the use of cerebrospinal fluid biomarkers in research memory center: the PLM Study.

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    Gabelle, Audrey; Dumurgier, Julien; Vercruysse, Olivier; Paquet, Claire; Bombois, Stéphanie; Laplanche, Jean-Louis; Peoc'h, Katell; Schraen, Susanna; Buée, Luc; Pasquier, Florence; Hugon, Jacques; Touchon, Jacques; Lehmann, Sylvain

    2013-01-01

    The French Alzheimer's Disease Plan aims, in an unprecedented national effort, to develop research, promote optimal diagnosis, and take better care of patients. In order to evaluate the clinical interest and use of cerebrospinal fluid (CSF) biomarkers, a data-sharing project, the PLM (Paris-North, Lille and Montpellier) study has emerged through collaboration between these memory centers, already involved in this field. The revised Alzheimer's disease (AD) diagnosis criteria include CSF biomarkers, but little is known about their use in routine clinical practice. To evaluate their interest and diagnostic accuracy in routine AD diagnosis, a cohort of 677 patients from Montpellier was first analyzed. The results were then validated through the analysis of a second cohort of 638 patients from Lille and Paris-Nord. Diagnoses of AD and other dementias were established by multidisciplinary expert teams, based on neuropsychological exams and structural brain imaging, blinded from CSF results. CSF amyloid-β, tau, and p-tau concentrations were measured for all patients. Receiver-operating characteristic curves were used to define cut-offs and evaluate the ability of each biomarker to discriminate AD from other diagnoses. We showed that p-tau outperformed other biomarkers for discriminating AD from non-AD patients and presents a clear clinical interest. The other biomarkers also showed relevant variations especially when the differential AD diagnoses were taken into account. Altogether we could demonstrate in both mono-centric and multi-centric cohorts from memory clinics the capacity of CSF biomarkers to discriminate AD from non-AD patients in clinical routine with a high sensitivity and specificity.

  8. Amyloid-β peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: A review of experimental and clinical studies

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    Parmenion P. Tsitsopoulos

    2013-06-01

    Full Text Available Traumatic brain injury (TBI survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP. Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ peptides, a hallmark finding in Alzheimer’s disease (AD. At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF using cerebral microdialysis and/or cerebrospinal fluid (CSF following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long

  9. Metallomic Biomarkers in Cerebrospinal fluid and Serum in patients with Parkinson’s disease in Indian population

    Science.gov (United States)

    Sanyal, Jaya; Ahmed, Shiek S. S. J.; Ng, Hon Keung Tony; Naiya, Tufan; Ghosh, Epsita; Banerjee, Tapas Kumar; Lakshmi, Jaya; Guha, Gautam; Rao, Vadlamudi Raghavendra

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disease with the absence of markers for diagnosis. Several studies on PD reported the elements imbalance in biofluids as biomarkers. However, their results remained inconclusive. This study integrates metallomics, multivariate and artificial neural network (ANN) to understand element variations in CSF and serum of PD patients from the largest cohort of Indian population to solve the inconsistent results of previous studies. Also, this study is aimed to (1) ascertain a common element signature between CSF and serum. (2) Assess cross sectional element variation with clinical symptoms. (3) Develop ANN models for rapid diagnosis. A metallomic profile of 110 CSF and 530 serum samples showed significant variations in 10 elements of CSF and six in serum of patients compared to controls. Consistent variations in elements pattern were noticed for Calcium, Magnesium and Iron in both the fluids of PD, which provides feasible diagnosis from serum. Furthermore, implementing multivariate analyses showed clear classification between normal and PD in both the fluids. Also, ANN provides 99% accuracy in detection of disease from CSF and serum. Overall, our analyses demonstrate that elements profile in biofluids of PD will be useful in development of diagnostic markers for PD. PMID:27752066

  10. Cerebrospinal fluid tau proteins in status epilepticus.

    Science.gov (United States)

    Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo F; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa

    2015-08-01

    Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus".

  11. Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease.

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    John S K Kauwe

    Full Text Available Recent genome-wide association studies of Alzheimer's disease (AD have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF 42 amino acid amyloid beta fragments (Aβ(42 and tau phosphorylated at threonine 181 (ptau(181, have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ(42 or ptau(181 levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ(42 or ptau(181.

  12. Leucine-rich α2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex.

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    Masakazu Miyajima

    Full Text Available Leucine-rich α2-glycoprotein (LRG is a protein induced by inflammation. It contains a leucine-rich repeat (LRR structure and easily binds with other molecules. However, the function of LRG in the brain during aging and neurodegenerative diseases has not been investigated. Here, we measured human LRG (hLRG concentration in the cerebrospinal fluid (CSF and observed hLRG expression in post-mortem human cerebral cortex. We then generated transgenic (Tg mice that over-expressed mouse LRG (mLRG in the brain to examine the effects of mLRG accumulation. Finally, we examined protein-protein interactions using a protein microarray method to screen proteins with a high affinity for hLRG. The CSF concentration of hLRG increases with age and is significantly higher in patients with Parkinson's disease with dementia (PDD and progressive supranuclear palsy (PSP than in healthy elderly people, idiopathic normal pressure hydrocephalus (iNPH patients, and individuals with Alzheimer's disease (AD. Tg mice exhibited neuronal degeneration and neuronal decline. Accumulation of LRG in the brains of PDD and PSP patients is not a primary etiological factor, but it is thought to be one of the causes of neurodegeneration. It is anticipated that hLRG CSF levels will be a useful biomarker for the early diagnosis of PDD and PSP.

  13. The interaction between sleep-disordered breathing and ApoE genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly

    Science.gov (United States)

    Osorio, Ricardo S.; Ayappa, Indu; Mantua, Janna; Gumb, Tyler; Varga, Andrew; Mooney, Anne M.; Burschtin, Omar E.; Taxin, Zachary; During, Emmanuel; Spector, Nicole; Biagioni, Milton; Pirraglia, Elizabeth; Lau, Hiuyan; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou-En; Mosconi, Lisa; Glodzik, Lidia; Rapoport, David M.; de Leon, Mony J.

    2014-01-01

    Background Previous studies have suggested a link between Sleep Disordered Breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers, and the ApoE alleles. Methods 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (P-Tau), total-tau (T-Tau), and amyloid beta 42 (Aβ42), as well as ApoE allele status. Findings In ApoE3+ subjects, significant differences were found between sleep groups for P-Tau (F[df2]=4.3, p=0.017), and T-Tau (F[df2]=3.3, p=0.043). Additionally, among ApoE3+ subjects, the apnea/hypopnea with 4% O2-desaturation index (AHI4%) was positively correlated with P-Tau (r=0.30, p=0.023), T-Tau (r=0.31, p=0.021), and Aβ42 (r=0.31, p=0.021). In ApoE2+ subjects, AHI4% was correlated with lower levels of CSF Aβ42 (r=−0.71, p=0.004), similarly to ApoE4+ subjects where there was also a trend towards lower CSF Aβ42 levels Interpretation Our observations suggest that there is an association between SDB and CSF AD- biomarkers in cognitively normal elderly. Existing therapies for SDB such as CPAP could delay the onset to mild cognitive impairment or dementia in normal elderly. PMID:24439479

  14. Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals.

    Science.gov (United States)

    Osorio, Ricardo S; Ayappa, Indu; Mantua, Janna; Gumb, Tyler; Varga, Andrew; Mooney, Anne M; Burschtin, Omar E; Taxin, Zachary; During, Emmanuel; Spector, Nicole; Biagioni, Milton; Pirraglia, Elizabeth; Lau, Hiuyan; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou-En; Mosconi, Lisa; Glodzik, Lidia; Rapoport, David M; de Leon, Mony J

    2014-06-01

    Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals. PMID:24439479

  15. Cerebrospinal fluid tau and phosphorylated tau protein are elevated in corticobasal syndrome

    NARCIS (Netherlands)

    Aerts, M.B.; Esselink, R.A.J.; Bloem, B.R.; Verbeek, M.M.

    2011-01-01

    Differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (PD) can be difficult. To investigate the additional value of cerebrospinal fluid (CSF) biomarkers in the diagnostic differentiation of parkinsonism, we analyzed the CSF concentra

  16. Minocycline effects on the cerebrospinal fluid proteome of experimental autoimmune encephalomyelitis rats

    NARCIS (Netherlands)

    Stoop, M.P.; Rosenling, T.; Attali, A.; Meesters, R.J.; Stingl, C.; Dekker, L.J.; Aken, H. van; Suidgeest, E.; Hintzen, R.Q.; Tuinstra, T.; Gool, A.J. van; Luider, T.M.; Bischoff, R.

    2012-01-01

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of neurolo

  17. Minocycline Effects on the Cerebrospinal Fluid Proteome of Experimental Autoimmune Encephalomyelitis Rats

    NARCIS (Netherlands)

    Stoop, Marcel P.; Rosenling, Therese; Attali, Amos; Meesters, Roland J. W.; Stingl, Christoph; Dekker, Lennard J.; van Aken, Hans; Suidgeest, Ernst; Hintzen, Rogier Q.; Tuinstra, Tinka; van Gool, Alain; Luider, Theo M.; Bischoff, Rainer

    2012-01-01

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of neurolo

  18. MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study

    OpenAIRE

    Richard, Edo; Ben A. Schmand; Eikelenboom, Piet; van Gool, Willem A.; ,

    2013-01-01

    Objectives To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. Design Diagnostic accuracy study in a multicentre prospective cohort study. Setting Alzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis. Participants Patients with mild cognitive impairment (MCI; n=181) ...

  19. MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study

    OpenAIRE

    E. Richard; Schmand, B.A.; Eikelenboom, P.; Gool, van, A.C.M.

    2013-01-01

    OBJECTIVES: To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. DESIGN: Diagnostic accuracy study in a multicentre prospective cohort study. SETTING: Alzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis. PARTICIPANTS: Patients with mild cognitive impairment (MCI; n=1...

  20. Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder

    OpenAIRE

    Shintaro Ogawa; Kotaro Hattori; Daimei Sasayama; Yuki Yokota; Ryo Matsumura; Junko Matsuo; Miho Ota; Hiroaki Hori; Toshiya Teraishi; Sumiko Yoshida; Takamasa Noda; Yoshiaki Ohashi; Hajime Sato; Teruhiko Higuchi; Nobutaka Motohashi

    2015-01-01

    Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the...

  1. The Maze of the Cerebrospinal Fluid Discovery

    Directory of Open Access Journals (Sweden)

    Leszek Herbowski

    2013-01-01

    Full Text Available The author analyzes a historical, long, and tortuous way to discover the cerebrospinal fluid. At least 35 physicians and anatomists described in the text have laid the fundamentals of recognition of this biological fluid’s presence. On the basis of crucial anatomical, experimental, and clinical works there are four greatest physicians who should be considered as equal cerebrospinal fluid’s discoverers: Egyptian Imhotep, Venetian Nicolo Massa, Italian Domenico Felice Cotugno, and French François Magendie.

  2. Cerebrospinal Fluid Proteomics of Multiple Sclerosis Patients

    NARCIS (Netherlands)

    M.P. Stoop (Marcel)

    2010-01-01

    textabstractMultiple sclerosis (MScl) is a highly heterogeneous disease of the central nervous system, and its pathology is characterized by a combination of factors such as inflammation, demyelination and axonal damage [1, 2]. Cerebrospinal fluid (CSF) is a relatively interesting body fluid in whic

  3. Limited cerebrospinal fluid penetration of docetaxel

    NARCIS (Netherlands)

    ten Tije, Albert J; Loos, Walter J; Zhao, Ming; Baker, Sharyn D; Enting, Roelien H; van der Meulen, Hans; Verweij, Jaap; Sparreboom, Alex; Enting, Roeline

    2004-01-01

    Our purpose was to investigate the cerebrospinal fluid (CSF) penetration of docetaxel in cancer patients. Docetaxel was administered as a 1-h infusion at a dose of 75 mg/m2 to two patients with metastatic breast cancer and leptomeningeal carcinomatosis. CSF samples were obtained using a lumbar punct

  4. Substance P in human cerebrospinal fluid

    International Nuclear Information System (INIS)

    Using a combined method of reversed-phase, high-pressure liquid chromatography and RIA, the author was able to isolate the neuropephide substance P from human cerebrospinal fluid and to make a quantitative measurement. The rp-HPLC-RIA method was found to be superior to other methods. (MBC)

  5. Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-beta Isoforms for Early and Differential Dementia Diagnosis

    NARCIS (Netherlands)

    Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P.; Streffer, Johannes R.; Mercken, Marc; Engelborghs, Sebastiaan

    2015-01-01

    Background: Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-beta (A beta) isoforms might improve the AD versus non-AD differential diagnosis. Objective: To de

  6. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function.

    Science.gov (United States)

    Yao, Xue; Yan, Licheng; Yao, Lin; Guan, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

    2014-03-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity. PMID:25206854

  7. CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE

    OpenAIRE

    Whedon, James M; Glassey, Donald

    2009-01-01

    We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste pro...

  8. High Blood Pressure Effects on the Blood to Cerebrospinal Fluid Barrier and Cerebrospinal Fluid Protein Composition: A Two-Dimensional Electrophoresis Study in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Ibrahim González-Marrero

    2013-01-01

    Full Text Available The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and β-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that α-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and α-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, α-2-HS-glycoprotein, transferrin, α-1β-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption.

  9. High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development

    Directory of Open Access Journals (Sweden)

    Keiro Shirotani

    2011-01-01

    Full Text Available We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf in cerebrospinal fluid (CSF using lectins and an anti-transferrin antibody (TfAb. Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin bound an unique N-acetylglucosamine-terminated N-glycans on “CSF-type” Tf whereas SSA (Sambucus sieboldiana agglutinin bound α2,6-N-acetylneuraminic acid-terminated N-glycans on “serum-type” Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected “CSF-type” Tf but not “serum-type” Tf whereas SSA-TfAb ELISA detected “serum-type” Tf but not “CSF-type” Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH, a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases.

  10. Active Cigarette Smoking in Cognitively-Normal Elders and Probable Alzheimer's Disease is Associated with Elevated Cerebrospinal Fluid Oxidative Stress Biomarkers.

    Science.gov (United States)

    Durazzo, Timothy C; Korecka, Magdalena; Trojanowski, John Q; Weiner, Michael W; O' Hara, Ruth; Ashford, John W; Shaw, Leslie M

    2016-07-25

    Neurodegenerative diseases and chronic cigarette smoking are associated with increased cerebral oxidative stress (OxS). Elevated F2-isoprostane levels in biological fluid is a recognized marker of OxS. This study assessed the association of active cigarette smoking with F2-isoprostane in concentrations in cognitively-normal elders (CN), and those with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD). Smoking and non-smoking CN (n = 83), MCI (n = 164), and probable AD (n = 101) were compared on cerebrospinal fluid (CSF) iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostane concentrations. Associations between F2-isoprostane levels and hippocampal volumes were also evaluated. In CN and AD, smokers had higher iPF2α-III concentration; overall, smoking AD showed the highest iPF2α-III concentration across groups. Smoking and non-smoking MCI did not differ on iPF2α-III concentration. No group differences were apparent on 8,12, iso-iPF2α-VI concentration, but across AD, higher 8,12, iso-iPF2α-VI level was related to smaller left and total hippocampal volumes. Results indicate that active cigarette smoking in CN and probable AD is associated with increased central nervous system OxS. Further investigation of factors mediating/moderating the absence of smoking effects on CSF F2-isoprostane levels in MCI is warranted. In AD, increasing magnitude of OxS appeared to be related to smaller hippocampal volume. This study contributes additional novel information to the mounting body of evidence that cigarette smoking is associated with adverse effects on the human central nervous system across the lifespan. PMID:27472882

  11. Cerebrospinal fluid phosphorylated tau proteins as predictors of Alzheimer’s disease in subjects with mild cognitive impairment

    OpenAIRE

    Šimić, Goran; Boban, Marina; Patrick R Hof

    2008-01-01

    Major efforts are under way to define reliable biomarkers of Alzheimer’s disease. Highly significant increases of hyperphosphorylated tau proteins in cerebrospinal fluid have been recently reported in Alzheimer’s disease patients compared to controls by several independent groups, including ours. These findings support the notion that cerebrospinal fluid phosphorylated tau proteins may be very useful biomarkers in the early identification of Alzheimer’s disease in patients with mild cognit...

  12. Extracranial repair of cerebrospinal fluid otorhinorrhea

    Energy Technology Data Exchange (ETDEWEB)

    Persky, M.S.; Rothstein, S.G.; Breda, S.D.; Cohen, N.L.; Cooper, P.; Ransohoff, J. (New York Univ. Medical Center, NY (USA))

    1991-02-01

    Forty-eight patients with cerebrospinal fluid leaks comprise this retrospective study. There were 39 traumatic and 9 spontaneous leaks. Nine patients were initially managed with bed rest and spinal drainage, but 3 patients in this group ultimately required surgical intervention for repair of their persistent leaks. Thirty-nine patients had surgery as initial therapy, with 33 extracranial repairs, 2 intracranial repairs, and 4 combined approaches. The extracranial approach was used in 36 of 42 patients, with an initial success rate of 86%.

  13. Cerebrospinal fluid stasis and its clinical significance.

    Science.gov (United States)

    Whedon, James M; Glassey, Donald

    2009-01-01

    We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste products of cellular metabolism, and transports hormones, neurotransmitters, releasing factors, and other neuropeptides throughout the CNS. Physiologic impedance or cessation of CSF flow may occur commonly in the absence of degenerative changes or pathology and may compromise the normal physiologic functions of the CSF. CSF appears to be particularly prone to stasis within the spinal canal. CSF stasis may be associated with adverse mechanical cord tension, vertebral subluxation syndrome, reduced cranial rhythmic impulse, and restricted respiratory function. Increased sympathetic tone, facilitated spinal segments, dural tension, and decreased CSF flow have been described as closely related aspects of an overall pattern of structural and energetic dysfunction in the axial skeleton and CNS. Therapies directed at affecting CSF flow include osteopathic care (especially cranial manipulation), craniosacral therapy, chiropractic adjustment of the spine and cranium, Network Care (formerly Network Chiropractic), massage therapy (including lymphatic drainage techniques), yoga, therapeutic breath-work, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted. PMID:19472865

  14. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

    OpenAIRE

    Yao, Xue; Yan, Licheng; Yao, Lin; GUAN, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

    2014-01-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospin...

  15. Spontaneous cerebrospinal fluid rhinorrhea in a patient with tentorial meningioma

    Institute of Scientific and Technical Information of China (English)

    GUNA Jing-yu; TONG Xiao-jie; WEI Xue-zhong

    2007-01-01

    @@ Spontaneous cerebrospinal fluid (CSF) rhinorrhea is rarely found, especially in patients with brain tumors.Similarly, reports of tentorial meningioma coexisting with acquired Chiari Ⅰ malformation with hydromyelia are also few. No doubt, one patient with cerebrospinal fluid rhinorrhea, tentorial meningioma and Chiari Ⅰ malformation with hydromyelia is hardly ever found. We reported one case of this rare condition.

  16. Cerebral venous outflow and cerebrospinal fluid dynamics

    Directory of Open Access Journals (Sweden)

    Clive B. Beggs

    2014-12-01

    Full Text Available In this review, the impact of restricted cerebral venous outflow on the biomechanics of the intracranial fluid system is investigated. The cerebral venous drainage system is often viewed simply as a series of collecting vessels channeling blood back to the heart. However there is growing evidence that it plays an important role in regulating the intracranial fluid system. In particular, there appears to be a link between increased cerebrospinal fluid (CSF pulsatility in the Aqueduct of Sylvius and constricted venous outflow. Constricted venous outflow also appears to inhibit absorption of CSF into the superior sagittal sinus. The compliance of the cortical bridging veins appears to be critical to the behaviour of the intracranial fluid system, with abnormalities at this location implicated in normal pressure hydrocephalus. The compliance associated with these vessels appears to be functional in nature and dependent on the free egress of blood out of the cranium via the extracranial venous drainage pathways. Because constricted venous outflow appears to be linked with increased aqueductal CSF pulsatility, it suggests that inhibited venous blood outflow may be altering the compliance of the cortical bridging veins.

  17. Imhotep and the discovery of cerebrospinal fluid.

    Science.gov (United States)

    Blomstedt, Patric

    2014-01-01

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

  18. Characterization of individual mouse cerebrospinal fluid proteomes

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeffrey S.; Angel, Thomas E.; Chavkin, Charles; Orton, Daniel J.; Moore, Ronald J.; Smith, Richard D.

    2014-03-20

    Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the central nervous system. Characterization of murine CSF proteomes can provide a valuable resource for studying central nervous system injury and disease in animal models. However, the small volume of CSF in mice has thus far limited individual mouse proteome characterization. Through non-terminal CSF extractions in C57Bl/6 mice and high-resolution liquid chromatography-mass spectrometry analysis of individual murine samples, we report the most comprehensive proteome characterization of individual murine CSF to date. Utilizing stringent protein inclusion criteria that required the identification of at least two unique peptides (1% false discovery rate at the peptide level) we identified a total of 566 unique proteins, including 128 proteins from three individual CSF samples that have been previously identified in brain tissue. Our methods and analysis provide a mechanism for individual murine CSF proteome analysis.

  19. Imhotep and the Discovery of Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Patric Blomstedt

    2014-01-01

    Full Text Available Herbowski (2013 suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned.

  20. Imhotep and the Discovery of Cerebrospinal Fluid

    Science.gov (United States)

    Blomstedt, Patric

    2014-01-01

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

  1. Studies of Cerebrospinal Fluid Biomarker in Amyotrophic Lateral Sclerosis%肌萎缩侧索硬化症脑脊液生物学标志物的研究

    Institute of Scientific and Technical Information of China (English)

    陈嬿; 蒋雨平

    2012-01-01

    Amyotrophic lateral sclerosis(ALS) is a sever neurodegenerative disease characterized by progressive selective degeneration of motor neurons. The etiology of ALS remains unknown and meaningful diagnostic markers and efficient treatments are lack. Cerebrospinal fluid(CSF) might reflect pathological alterations in the central nervous system and easy to acquire . So study on CSF may helpful for the diagnosis of ALS and provide clues to the investigation of pathogenesis. This review mainly focused on the study of the CSF biomarkers of ALS.%肌萎缩侧索硬化症(ALS)是一种以选择性运动神经元变性为特征的神经退行性疾病.其病因和发病机制目前仍不明确,且缺乏客观的诊断标准和有效的治疗手段.脑脊液(CSF)能反映中枢神经系统病理生理改变,进行CSF中ALS生物学标志物的筛选将有助于疾病的诊断,为ALS发病机制的探讨提供线索.本文就近年来对ALS患者CSF中生物学标志物的研究作介绍.

  2. Proteome analysis of chick embryonic cerebrospinal fluid.

    Science.gov (United States)

    Parada, Carolina; Gato, Angel; Aparicio, Mariano; Bueno, David

    2006-01-01

    During early stages of embryo development, the brain cavity is filled with embryonic cerebrospinal fluid (E-CSF), a complex fluid containing different protein fractions that contributes to the regulation of the survival, proliferation and neurogenesis of the neuroectodermal stem cells. Using 2-DE, protein sequencing and database searches, we identified and analyzed the proteome of the E-CSF from chick embryos (Gallus gallus). We identified 26 different gene products, including proteins related to the extracellular matrix, proteins associated with the regulation of osmotic pressure and metal transport, proteins related to cell survival, MAP kinase activators, proteins involved in the transport of retinol and vitamin D, antioxidant and antimicrobial proteins, intracellular proteins and some unknown proteins. Most of these gene products are involved in the regulation of developmental processes during embryogenesis in systems other than E-CSF. Interestingly, 14 of them are also present in adult human CSF proteome, and it has been reported that they are altered in the CSF of patients suffering neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis is a key contribution to the general understanding of CNS development, and may also contribute to greater knowledge of these human diseases. PMID:16287170

  3. Cerebrospinal fluid composition modifications after neuroendoscopic procedures.

    Science.gov (United States)

    Salvador, L; Valero, R; Carrero, E; Caral, L; Fernández, S; Marín, J L; Ferrer, E; Fábregas, N

    2007-02-01

    Normal saline solution is currently used as the ventricular irrigation fluid during neuroendoscopic procedures. The aim of this study is to determine the alterations in the cerebrospinal fluid (CSF) composition after neuroendoscopic interventions. Twenty nine patients who underwent a neuroendoscopic procedure under general anaesthesia were studied. Temperature inside the cerebral ventricle was measured and samples of CSF were taken to determinate oxygen and carbon dioxide partial pressures, pH, base excess, ionised calcium, standard bicarbonate, glucose, sodium, potassium, magnesium, total calcium, proteins, chlorine and osmolality before initiating the irrigation and after the neuronavigation. Patient demographics, neuronavigation time, total fluid volume used and temperature of the irrigation solution and complications that appeared in the first 24 hours were collected. Mean age of the patients was 42+/-18 years. The mean neuronavigation time was 21.5+/-15.4 minutes. The mean amount of saline solution used for irrigation was 919.6+/-994.7 mL. All the values studied in the CSF, except osmolality, showed significant variations. There was a significant correlation between the CSF variation of pH, oxygen and carbon dioxide partial pressures, base excess, standard bicarbonate, glucose and total calcium with respect to the total volume of irrigation solution, but not with respect to the neuronavigation time. A cut-off point of 500 mL of irrigation solution (sensitivity 0.7; specificity 0.87) was related with a CSF pH decrease greater than 0.2. The use of saline as irrigation solution during neuroendoscopic procedures produces important changes in CSF. PMID:17546545

  4. Cerebrospinal fluid monoamine metabolites and suicide.

    Science.gov (United States)

    Jokinen, Jussi; Nordström, Anna-Lena; Nordström, Peter

    2009-01-01

    Prospective studies of the serotonergic system and suicide report that low 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and a history of attempted suicide predict suicide risk. Low CSF homovanillic acid (HVA) is reported to be associated with past and future lethality of suicide attempts but not with suicide. The interrelationships between monoamine metabolites, violent method, suicide intent and lethality of suicidal behaviour are complex. We hypothesized that CSF 5-HIAA and HVA levels are related to suicide intent, violence and lethality of suicidal behaviour. Fifteen male suicide attempters admitted to a psychiatric ward at the Karolinska University Hospital and eight healthy male volunteers were submitted to lumbar puncture and CSF 5-HIAA and HVA were assayed. Suicide intent with the Beck Suicide Intent Scale (SIS), lethality and violence of suicidal behaviour were assessed. All patients were followed up for causes of death. Six suicides and one fatal accident were identified with death certificates. Mean CSF 5-HIAA but not CSF HVA differed between suicides and survivors. Violent suicides had higher suicide intent and CSF 5-HIAA than non-violent suicides. In violent suicides, CSF 5-HIAA levels were negatively correlated with SIS. Greater suicide intent may be associated with greater aggressive intent and predicts a violent suicide method. PMID:19034712

  5. Malignancy markers in the cerebrospinal fluid.

    Science.gov (United States)

    Koskiniemi, M

    1988-10-01

    The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant. PMID:3058481

  6. Quantitative evaluation fo cerebrospinal fluid shunt flow

    Energy Technology Data Exchange (ETDEWEB)

    Chervu, S.; Chervu, L.R.; Vallabhajosyula, B.; Milstein, D.M.; Shapiro, K.M.; Shulman, K.; Blaufox, M.D.

    1984-01-01

    The authors describe a rigorous method for measuring the flow of cerebrospinal fluid (CSF) in shunt circuits implanted for the relief of obstructive hydrocephalus. Clearance of radioactivity for several calibrated flow rates was determined with a Harvard infusion pump by injecting the Rickham reservoir of a Rickham-Holter valve system with 100 ..mu..Ci of Tc-99m as pertechnetate. The elliptical and the cylindrical Holter valves used as adjunct valves with the Rickham reservoir yielded two different regression lines when the clearances were plotted against flow rats. The experimental regression lines were used to determine the in vivo flow rates from clearances calculated after injecting the Rickham reservoirs of the patients. The unique clearance characteristics of the individual shunt systems available requires that calibration curves be derived for an entire system identical to one implanted in the patient being evaluated, rather than just the injected chamber. Excellent correlation between flow rates and the clinical findings supports the reliability of this method of quantification of CSF shunt flow, and the results are fully accepted by neurosurgeons.

  7. Diagnostic value of circulating tumor cells in cerebrospinal fluid

    OpenAIRE

    Ning Mu; Chunhua Ma; Rong Jiang; Yuan Lv; Jinduo Li; Bin Wang; Liwei Sun

    2016-01-01

    To assess circulating tumor cells in cerebrospinal fluid as a diagnostic approach to identify meningeal metastasis in patients with non-small cell lung cancer by using tumor marker immunostaining–fluorescence in situ hybridization (TM-iFISH).

  8. Cerebrospinal fluid obstruction and malabsorption in human neonatal hydrocephaly

    NARCIS (Netherlands)

    Heep, Axel; Bartmann, Peter; Stoffel-Wagner, Birgit; Bos, Arie; Hoving, Eelco; Brouwer, Oebele; Teelken, Albert; Schaller, Carlo; Sival, Deborah

    2006-01-01

    Introduction: The pathophysiology involved in human neonatal high-pressure hydrocephalus (HC) includes both cerebrospinal fluid (CSF) malabsorption and obstruction. Objective: The aim was to estimate the relative contribution between CSF malabsorption and obstruction in three different etiological g

  9. Continuous cerebrospinal fluid drainage by spinal puncture for cerebrospinal fluid rhinorrhea after pituitary adenoma surgery

    Institute of Scientific and Technical Information of China (English)

    Zhengnian Ding; Weixing Hu

    2005-01-01

    Objective: Cerebrospinal fluid (CSF) rhinorrhea may be a serious complication after neurosurgery. Some of them can be treated conservatively by continuous CSF drainage with a lumbar subarachnoid catheter. On the other hand, spinal puncture may result in headache by CSF leakage. Methods: Present a 17-year-old female who suffered from CSF rhinorrhea after pituitary surgery was treated by making use of spinal puncture after failed catheter drainage. Results: The patient was successfully treated by this way.Conclusion: Spinal puncture by 16-gauge Touhy needle seems to be a possible way to substitute the traditional continuous lumbar subarachnoid catheter to drain the CSF in patients with rhinorrhea.

  10. The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging.

    Science.gov (United States)

    Gordon, Brian A; Friedrichsen, Karl; Brier, Matthew; Blazey, Tyler; Su, Yi; Christensen, Jon; Aldea, Patricia; McConathy, Jonathan; Holtzman, David M; Cairns, Nigel J; Morris, John C; Fagan, Anne M; Ances, Beau M; Benzinger, Tammie L S

    2016-08-01

    The two primary molecular pathologies in Alzheimer's disease are amyloid-β plaques and tau-immunoreactive neurofibrillary tangles. Investigations into these pathologies have been restricted to cerebrospinal fluid assays, and positron emission tomography tracers that can image amyloid-β plaques. Tau tracers have recently been introduced into the field, although the utility of the tracer and its relationship to other Alzheimer biomarkers are still unknown. Here we examined tau deposition in 41 cognitively normal and 11 cognitively impaired older adults using the radioactive tau ligand (18)F-AV-1451 (previously known as T807) who also underwent a lumbar puncture to assess cerebrospinal fluid levels of total tau (t-tau), phosphorylated tau181 (p-tau181) and amyloid-β42 Voxel-wise statistical analyses examined spatial patterns of tau deposition associated with cognitive impairment. We then related the amount of tau tracer uptake to levels of cerebrospinal fluid biomarkers. All analyses controlled for age and gender and, when appropriate, the time between imaging and lumbar puncture assessments. Symptomatic individuals (Clinical Dementia Rating > 0) demonstrated markedly increased levels of tau tracer uptake. This elevation was most prominent in the temporal lobe and temporoparietal junction, but extended more broadly into parietal and frontal cortices. In the entire cohort, there were significant relationships among all cerebrospinal fluid biomarkers and tracer uptake, notably for tau-related cerebrospinal fluid markers. After controlling for levels of amyloid-β42, the correlations with tau uptake were r = 0.490 (P Alzheimer's disease, there is focal tauopathy in the medial temporal lobes and adjacent cortices. PMID:27286736

  11. Biomarkers of Alzheimer’s disease in body fluids

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.

  12. Praziquantel in the cerebrospinal fluid in neurocysticercosis

    Directory of Open Access Journals (Sweden)

    A. Spina-França

    1985-09-01

    Full Text Available In 10 patients with neurocysticercosis (NC, an assessment was made of the praziquantel (PZQ concentration in the cerebrospinal fluid (CSF, in non-deproteinized serum and in protein-free serum: before administration of the drug and the 1st., 7th. and 21st. days of oral administration (50mg/kg/day during 21 days. Samples of CSF and blood were collected three hours after the last administration of the daily total dosage, on the 1st. and 21st days; and from 2 to 6 hours after drug administration on the 7th. day. The total daily dosage was distributed into three equal parts of 1/3 each, with a 4 hours' interval between intakes, except in the last 5 cases, who on the 21st. day only were given the total daily dosage on a single administration. Results have shown dispersion in serum concentrations, which are similar to those seen in normal subjects as recorded in literature. There is a correlation between PZQ levels in the CSF and in the serum, the latter being very close to those found in protein-free serum fraction. The statistical treatment of results allowed the following considerations: PZQ concentrations in the CSF and in the protein free serum are in balance from the pharmacodynamic standpoint on the first day; this balance is maintained up to the 21st. day although at different levels from those seen on the 7th. day; on the 21st. day PZQ contents in CSF goes back to its similar values as recorded on the 1st. day, and this suggests that the participation of drug interaction factors has been reduced to non-significant levels. However, several factors can influence PZQ concentration in CSF, as absorption rate, liver first-pass effect and blood-brain barrier changes, and individual dose should be established for each patient based on drug concentration monitoring in the serum and/or in the CSF.

  13. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8, incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches

  14. Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS

    Directory of Open Access Journals (Sweden)

    Fujino Osamu

    2011-08-01

    Full Text Available Abstract Background Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF of children with encephalopathy using proteomic analysis. Methods For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations. Results In experiment 1, CSF from patients with febrile seizures (n = 28, patients with encephalopathy (n = 8 (including influenza encephalopathy (n = 3, encephalopathy due to rotavirus (n = 1, human herpes virus 6 (n = 1 were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14 and encephalopathy patients (n = 5. We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8 was identified as a novel biomarker for encephalopathy. Conclusions

  15. Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

    Science.gov (United States)

    Zanello, S. B.; Stevens, B.; Calvillo, E.; Tang, R.; Gutierrez Flores, B.; Hu, L.; Skog, J.; Bershad, E.

    2016-01-01

    While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for

  16. Cerebrospinal fluid cytology studies of neuropsychiatric systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    CHEN Lin

    2013-02-01

    Full Text Available Background Neuropsychiatric systemic lupus erythematosus (NP-SLE is the central nervous system (CNS involvement of systemic lupus erythematosus (SLE. The diagnosis of NP-SLE may be difficult due to the lack of specific biomarker. CNS cerebrospinal fluid (CSF cytology is diagnostic significant to CNS autoimmune disease. This paper described the characteristics of CSF cytology and evaluated its diagnostic value in NP-SLE. Methods Seventy-six eligible patients with clear diagnosis of NP-SLE were collected for CSF cytological examinations. Results The CSF cytology findings of 25 cases in 76 were abnormal, among which 16 cases showed lymphocytic inflammatory reactions; 8 cases had slight increase of neutrophile granulocyte percent; 9 cases showed lymphocyte-neutrophile inflammation. Activated lymphocytes together with monocytes were present in 24 cases. Among those cases, abnormal endocytosis of monocytes, which presented as monocytes phagocytosing lymphocytes or plasmocytes, was shown in 17 cases; plasmocytes were found in 17 cases. Conclusion The diagnosis of NP-SLE is based on clinical, neuroimaging and CSF studies. Among these methods, the CSF cytology findings are quite useful in practice, since the CSF cytological inflammatory reactions, especially the presentation of abnormal phagocytes in CSF is typical in NP-SLE and indicates its vasculitic mechanism.

  17. The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Gray, Elizabeth; Larkin, James R; Claridge, Tim D W; Talbot, Kevin; Sibson, Nicola R; Turner, Martin R

    2015-01-01

    Neurochemical biomarkers are urgently sought in ALS. Metabolomic analysis of cerebrospinal fluid (CSF) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy is a highly sensitive method capable of revealing nervous system cellular pathology. The (1)H-NMR CSF metabolomic signature of ALS was sought in a longitudinal cohort. Six-monthly serial collection was performed in ALS patients across a range of clinical sub-types (n = 41) for up to two years, and in healthy controls at a single time-point (n = 14). A multivariate statistical approach, partial least squares discriminant analysis, was used to determine differences between the NMR spectra from patients and controls. Significantly predictive models were found using those patients with at least one year's interval between recruitment and the second sample. Glucose, lactate, citric acid and, unexpectedly, ethanol were the discriminating metabolites elevated in ALS. It is concluded that (1)H-NMR captured the CSF metabolomic signature associated with derangements in cellular energy utilization connected with ALS, and was most prominent in comparisons using patients with longer disease duration. The specific metabolites identified support the concept of a hypercatabolic state, possibly involving mitochondrial dysfunction specifically. Endogenous ethanol in the CSF may be an unrecognized novel marker of neuronal tissue injury in ALS.

  18. Cerebrospinal fluid PKR level predicts cognitive decline in Alzheimer's disease.

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    Julien Dumurgier

    Full Text Available The cerebrospinal fluid (CSF levels of the proapoptotic kinase R (PKR and its phosphorylated PKR (pPKR are increased in Alzheimer's disease (AD, but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of Aβ peptide (Aβ 1-42, Tau, phosphorylated Tau (p-Tau 181, PKR and pPKR. The mean (SD MMSE at baseline was 20.5 (6.1 and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE] = 0.03. A lower MMSE at baseline was associated with lower levels of CSF Aβ 1-42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.

  19. Preliminary analysis of cerebrospinal fluid proteome in patients with neurocysticercosis

    Institute of Scientific and Technical Information of China (English)

    TIAN Xiao-jun; LI Jing-yi; HUANG Yong; XUE Yan-ping

    2009-01-01

    Background Neurocysticercosis is the infection of the nervous system by the larvae of Taenia solium (T. solium). Despite continuous effort, the experimental diagnosis of neurocysticercosis remains unresolved. Since the cerebrospinal fluid (CSF) contacts with the brain, dynamic information about pathological processes of the brain is likely to be reflected in CSF. Therefore, CSF may serve as a rich source of putative biomarkers related to neurocysticercosis. Comparative proteomic analysis of CSF of neurocysticercosis patients and control subjects may find differentially expressed proteins. Methods Two-dimensional difference in gel electrophoresis (2D-DIGE) was used to investigate differentially expressed proteins in CSF of patients with neurocysticercosis by comparing the protein profile of CSF from neurocysticercosis patients with that from control subjects. The differentially expressed spots/proteins were recognized with matrix-assisted laser desorption/ionization-time of flight-time of flight (MALDI-TOF-TOF) mass spectrometry. Results Forty-four enzyme digested peptides were obtained from 4 neurocysticercotic patients. Twenty-three were identified through search of the NCBI protein database with Mascot software, showing 19 up-expressed and 4 down-expressed. Of these proteins, 26S proteosome related to ATP- and ubiquitin-dependent degradation of proteins and lipocalin type prostaglandin D synthase involved in PGD2-synthesis and extracellular transporter activities were up-expressed, while transferrin related to iron metabolism within the brain was down-expressed. Conclusions This study established the proteomic profile of pooled CSF from 4 patients with neurocysticercosis, suggesting the potential value of proteomic analysis for the study of candidate biomarkers involved in the diagnosis or pathogenesis of neurocysticercosis.

  20. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen;

    2015-01-01

    To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact...

  1. Entamoeba histolytica meningoencephalitis diagnosed by trophozoites in cerebrospinal fluid

    OpenAIRE

    Goh, L M L; Marrone, J R

    2013-01-01

    Entamoeba histolytica meningoencephalitis has not been described in the modern literature, which is distinct from that caused by free-living amoebae. We report the first case of E. histolytica meningoencephalitis without liver or brain abscesses. Cerebrospinal fluid revealed 2 + very motile trophozoites. Our patient was successfully treated with intravenous metronidazole.

  2. Ongoing HIV replication in cerebrospinal fluid under successful monotherapy

    NARCIS (Netherlands)

    M. Bierhoff (Marieke); C.A.B. Boucher (Charles); A. Fibriani (Azzania); R.W. ten Kate (Reinier)

    2013-01-01

    textabstractWe report a case of an HIV-infected patient who was successfully treated with ritonavir/lopinavir (r/LPV) monotherapy for several years. He presented with neurological symptoms and high HIV RNA levels in cerebrospinal fluid (CSF). Sequencing of the HIV from the CSF revealed mutations in

  3. [Diagnostic significance of immunologic study of cerebrospinal fluid in neuroinfections].

    Science.gov (United States)

    Dekonenko, E P; Umanskiĭ, K G; Andreeva, L S

    1985-01-01

    An increase in the antibody titre in the blood serum, previously considered sufficient for determining the etiology of neuroinfection can no longer be regarded as a satisfactory index in the light of the contemporary level of our knowledge. The literature and the authors' own data show the importance of a simultaneous examination of antibodies in the cerebrospinal fluid and the blood serum in some neuroinfections. For example, the determination in the cerebrospinal fluid of antibodies to herpes simplex virus in herpetic encephalitis is considered sufficient (in the presence of the characteristic clinical picture) to make the diagnosis of this severe disease. The examination of antibodies to herpes simplex virus in the cerebrospinal fluid of 35 patients with a suspected herpetic encephalitis revealed their presence in 34% of those studied. The data obtained suggest that immunoassay of the cerebrospinal fluid and blood sera should be used on a broader scale in patients with acute and chronic neuroinfections. The method plays an the early diagnosis of these diseases and early administration of the appropriate treatment.

  4. Population Pharmacokinetics of Abacavir in Plasma and Cerebrospinal Fluid

    OpenAIRE

    Capparelli, Edmund V; Letendre, Scott L.; ELLIS, Ronald J.; Patel, Parul; Holland, Diane; MCCUTCHAN, J. Allen

    2005-01-01

    The distribution of abacavir into the cerebrospinal fluid (CSF) was assessed by use of a population pharmacokinetic analysis. Plasma and CSF abacavir concentrations in 54 subjects were determined. The abacavir CSF/plasma ratio averaged 36% and increased throughout the dose interval. Abacavir penetrates into the CSF in adequate concentrations to inhibit local human immunodeficiency virus replication.

  5. Factors influencing the measurement of lysosomal enzymes activity in human cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Emanuele Persichetti

    Full Text Available Measurements of the activities of lysosomal enzymes in cerebrospinal fluid have recently been proposed as putative biomarkers for Parkinson's disease and other synucleinopathies. To define the operating procedures useful for ensuring the reliability of these measurements, we analyzed several pre-analytical factors that may influence the activity of β-glucocerebrosidase, α-mannosidase, β-mannosidase, β-galactosidase, α-fucosidase, β-hexosaminidase, cathepsin D and cathepsin E in cerebrospinal fluid. Lysosomal enzyme activities were measured by well-established fluorimetric assays in a consecutive series of patients (n = 28 with different neurological conditions, including Parkinson's disease. The precision, pre-storage and storage conditions, and freeze/thaw cycles were evaluated. All of the assays showed within- and between-run variabilities below 10%. At -20°C, only cathepsin D was stable up to 40 weeks. At -80°C, the cathepsin D, cathepsin E, and β-mannosidase activities did not change significantly up to 40 weeks, while β-glucocerebrosidase activity was stable up to 32 weeks. The β-galactosidase and α-fucosidase activities significantly increased (+54.9±38.08% after 4 weeks and +88.94±36.19% after 16 weeks, respectively. Up to four freeze/thaw cycles did not significantly affect the activities of cathepsins D and E. The β-glucocerebrosidase activity showed a slight decrease (-14.6% after two freeze/thaw cycles. The measurement of lysosomal enzyme activities in cerebrospinal fluid is reliable and reproducible if pre-analytical factors are accurately taken into consideration. Therefore, the analytical recommendations that ensue from this study may contribute to the establishment of actual values for the activities of cerebrospinal fluid lysosomal enzymes as putative biomarkers for Parkinson's disease and other neurodegenerative disorders.

  6. Cerebrospinal fluid interleukin-6 in central nervous system inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Alexandre Wullschleger

    Full Text Available BACKGROUND: Interleukin (IL-6 is recognised as an important cytokine involved in inflammatory diseases of the central nervous system (CNS. OBJECTIVE: To perform a large retrospective study designed to test cerebrospinal fluid (CSF IL-6 levels in the context of neurological diseases, and evaluate its usefulness as a biomarker to help discriminate multiple sclerosis (MS from other inflammatory neurological diseases (OIND. PATIENTS AND METHODS: We analyzed 374 CSF samples for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested were composed of demyelinating diseases of the CNS (DD, n = 117, including relapsing-remitting MS (RRMS, n = 65, primary progressive MS (PPMS, n = 11, clinically isolated syndrome (CIS, n = 11, optic neuritis (ON, n = 30; idiopathic transverse myelitis (ITM, n = 10; other inflammatory neurological diseases (OIND, n = 35; and non-inflammatory neurological diseases (NIND, n = 212. Differences between groups were analysed using Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: CSF IL-6 levels exceeded the positivity cut-off of 10 pg/ml in 18 (51.4% of the 35 OIND samples, but in only three (3.9% of the 76 MS samples collected. CSF IL-6 was negative for all NIND samples tested (0/212. IL-6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS. CONCLUSION: CSF IL-6 may help to differentiate MS from its major differential diagnosis group, OIND.

  7. Cerebrospinal fluid drainage through the diploic and spinal epidural veins.

    Science.gov (United States)

    Tsutsumi, Satoshi; Ogino, Ikuko; Miyajima, Masakazu; Ito, Masanori; Arai, Hajime; Yasumoto, Yukimasa

    2015-09-01

    The aim of this study was to quantitatively evaluate the function of the cranial diploic and spinal epidural veins as cerebrospinal fluid (CSF) drainage pathways by measuring lipocalin-type prostaglandin D synthase (PGDS) and cystatin C (CysC) dissolved in the blood of these veins. This was a prospective study involving 51 consecutive patients, 31 males and 20 females, who underwent 41 cranial and 10 spinal surgeries. Intraoperatively, peripheral venous blood and diploic venous blood, or peripheral venous blood and spinal epidural venous blood samples were simultaneously collected and immediately centrifuged. For all samples, dissolved albumin (for reference), PGDS and CysC were measured using an enzyme-linked immunosorbent assay. The diploic vein/peripheral vein ratios in five cranial locations and epidural vein/peripheral vein ratios were calculated and statistically evaluated for the three biomarkers. For PGDS, the diploic vein/peripheral vein ratio was significantly increased in the frontal (P = 0.011), temporal (P = 0.028), parietal (P = 0.046) and skull base (P = 0.039), while it did not reach statistical significance for CysC. For patients older than 45 years, the diploic vein/peripheral vein ratio for PGDS was significantly decreased in the frontal region (P = 0.028), and the epidural vein/peripheral vein ratio for CysC was significantly decreased (P = 0.014). These results show that the diploic veins constitute CSF drainage pathways with heterogeneous functional intensity at different cranial locations. Compared with the diploic veins, spinal epidural veins seem to drain less CSF. The cranial diploic and spinal epidural veins may jointly function as an alternative, age-related trans-dural CSF drainage system. PMID:26184099

  8. Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.

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    Christiane Mühle

    Full Text Available BACKGROUND: As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. METHODS: An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. RESULTS: We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme's properties. The enzyme resembles plasmatic ASM including protein stability and Zn(2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. CONCLUSIONS: Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.

  9. Identification and proteomic profiling of exosomes in human cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Street Jonathan M

    2012-01-01

    Full Text Available Abstract Background Exosomes are released from multiple cell types, contain protein and RNA species, and have been exploited as a novel reservoir for disease biomarker discovery. They can transfer information between cells and may cause pathology, for example, a role for exosomes has been proposed in the pathophysiology of Alzheimer's disease. Although studied in several biofluids, exosomes have not been extensively studied in the cerebrospinal fluid (CSF from humans. The objective of this study was to determine: 1 whether human CSF contains exosomes and 2 the variability in exosomal protein content across individuals. Methods CSF was collected from 5 study participants undergoing thoraco-abdominal aortic aneurysm repair (around 200 - 500 ml per participant and low-density membrane vesicles were concentrated by ultracentrifugation. The presence of exosomes was determined by western blot for marker proteins, isopycnic centrifugation on a sucrose step gradient and transmission electron microscopy with immuno-labelling. Whole protein profiling was performed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR. Results Flotillin 1 and tumor susceptibility gene 101 (TSG101, two exosomal marker proteins, were identified in the ultracentrifugation pellet using western blot. These markers localized to a density consistent with exosomes following isopycnic centrifugation. Transmission electron microscopy visualized structures consistent with exosomes in size and appearance that labelled positive for flotillin 1. Therefore, the pellet that resulted from ultracentrifugation of human CSF contained exosomes. FT-ICR profiling of this pellet was performed and 84-161 ions were detected per study participant. Around one third of these ions were only present in a single study participant and one third were detected in all five. With regard to ion quantity, the median coefficient of variation was 81% for ions detected in two or more samples

  10. Proteomic Analysis of Alzheimer’s Disease Cerebrospinal Fluid from Neuropathologically Diagnosed Subjects

    Science.gov (United States)

    Maarouf, Chera L.; Andacht, Tracy M.; Kokjohn, Tyler A.; Castaño, Eduardo M.; Sue, Lucia I.; Beach, Thomas G.; Roher, Alex E.

    2010-01-01

    A crucial need exists for reliable Alzheimer’s disease (AD) diagnostic and prognostic tests. Given its intimate communication with the brain, the cerebrospinal fluid (CSF) has been surveyed intensively for reliable AD biomarkers. The heterogeneity of AD pathology and the unavoidable difficulties associated with the clinical diagnosis and differentiation of this dementia from other pathologies have confounded biomarker studies in antemortem CSF samples. Using postmortem ventricular CSF (V-CSF) pools, two-dimensional difference gel electrophoresis (2D DIGE) analyses revealed a set of proteins that showed significant differences between neuropathologically-diagnosed AD and elderly non-demented controls (NDC), as well as subjects with non-AD dementias. The 2D DIGE system identified a set of 21 different protein biomarkers. This panel of proteins probably reflects fundamental pathological changes that are divergent from both normal aging and non-AD dementias. PMID:19689240

  11. A novel unbiased proteomic approach to detect the reactivity of cerebrospinal fluid in neurological diseases.

    Science.gov (United States)

    Menon, Krishnakumar N; Steer, David L; Short, Martin; Petratos, Steven; Smith, Ian; Bernard, Claude C A

    2011-06-01

    Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as αβ crystallin, enolase, and 14-3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin

  12. Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

    Directory of Open Access Journals (Sweden)

    Sandro Luiz de Andrade Matas

    2013-09-01

    Full Text Available The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS, neuromyelitis optic (NMO and acute disseminated encephalomyelitis (ADEM. The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

  13. Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

    OpenAIRE

    Sandro Luiz de Andrade Matas; Felipe von Glehn; Gustavo Bruniera Peres Fernandes; Carlos Augusto Senne Soares

    2013-01-01

    The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS), neuromyelitis optic (NMO) and acute disseminated encephalomyelitis (ADEM). The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the pro...

  14. Vitamin B6 in plasma and cerebrospinal fluid of children

    OpenAIRE

    Monique Albersen; Marjolein Bosma; Jans, Judith J. M.; Hofstede, Floris C.; van Hasselt, Peter M.; de Sain-van der Velden, Monique G. M.; Gepke Visser; Verhoeven-Duif, Nanda M.

    2015-01-01

    Background Over the past years, the essential role of vitamin B6 in brain development and functioning has been recognized and genetic metabolic disorders resulting in functional vitamin B6 deficiency have been identified. However, data on B6 vitamers in children are scarce. Materials and Methods B6 vitamer concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF) of 70 children with intellectual disability were determined by ultra performance liquid chromatography-tandem m...

  15. Swiftly Decreasing Cerebrospinal Fluid Cathelicidin Concentration Predicts Improved Outcome in Childhood Bacterial Meningitis.

    Science.gov (United States)

    Savonius, Okko; Helve, Otto; Roine, Irmeli; Andersson, Sture; Fernández, Josefina; Peltola, Heikki; Pelkonen, Tuula

    2016-06-01

    We investigated cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis on admission and during antimicrobial treatment. CSF cathelicidin concentrations on admission correlated with CSF white cell counts and protein levels but not with bacterial etiology. A greater decrease in the concentration in response to treatment was associated with a better outcome. Since the CSF cathelicidin concentration reflects the degree of central nervous system (CNS) inflammation, it may be used as a novel biomarker in childhood bacterial meningitis. An early decrease during treatment likely signals more rapid mitigation of the disease process and thus a better outcome. PMID:27008883

  16. Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

    DEFF Research Database (Denmark)

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês;

    2015-01-01

    Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild...... cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau...

  17. A plasma polymerization technique to overcome cerebrospinal fluid shunt infections

    Energy Technology Data Exchange (ETDEWEB)

    Coekeliler, D [Plasma Aided Bioengineering and Biotechnology Research Laboratory, Engineering Faculty, Hacettepe University, 06532, Ankara (Turkey); Caner, H [Department of Neurosurgery, School of Medicine, Baskent University, 06610, Ankara (Turkey); Zemek, J [Institute of Physics, Academy of Sciences of the Czech Republic, Cukrovarnicka 10, 162 53, Prague, Czech Republic (Czech Republic); Choukourov, A [Department of Macromolecular Physics, Charles University, V Holesovickach 2, 18000 Prague (Czech Republic); Biederman, H [Department of Macromolecular Physics, Charles University, V Holesovickach 2, 18000 Prague (Czech Republic); Mutlu, M [Plasma Aided Bioengineering and Biotechnology Research Laboratory, Engineering Faculty, Hacettepe University, 06532, Ankara (Turkey)

    2007-03-01

    Prosthetic devices, mainly shunts, are frequently used for temporary or permanent drainage of cerebrospinal fluid. The pathogenesis of shunt infection is a very important problem in modern medicine and generally this is characterized by staphylococcal adhesion to the cerebrospinal fluid shunt surfaces. In this paper, the prevention of the attachment of test microorganism Staphylococcus epidermidis on the cerebrospinal fluid shunt surfaces by 2-hydroxyethylmethacrylate (HEMA) precursor modification in the plasma polymerization system, is reported. Different plasma polymerization conditions (RF discharge power 10-20-30 W, exposure time 5-10-15 min) were employed during the surface modification. The surface chemistry and topology of unmodified and modified shunts was characterized by x-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and atomic force microscopy (AFM). Also, static contact angle measurements were performed to state the change of surface hydrophilicity. All samples were tested in vitro with Staphylococcus epidermidis. A plasma-polymerized HEMA film (PP HEMA) was found to be an alternative simple method to decrease the microorganism attachment and create bacterial anti-fouling surfaces. The attachment of the model microorganism Staphylococcus epidermidis on the shunt surface modified by PP HEMA at 20 W and 15 min was reduced 62.3% if compared to the unmodified control surface of the shunt.

  18. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study.

    Science.gov (United States)

    Leuzy, Antoine; Chiotis, Konstantinos; Hasselbalch, Steen G; Rinne, Juha O; de Mendonça, Alexandre; Otto, Markus; Lleó, Alberto; Castelo-Branco, Miguel; Santana, Isabel; Johansson, Jarkko; Anderl-Straub, Sarah; von Arnim, Christine A F; Beer, Ambros; Blesa, Rafael; Fortea, Juan; Herukka, Sanna-Kaisa; Portelius, Erik; Pannee, Josef; Zetterberg, Henrik; Blennow, Kaj; Nordberg, Agneta

    2016-09-01

    The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40 Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer's and Parkinson's Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference

  19. Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Anders Jens

    2001-12-01

    Full Text Available Abstract Background Most test systems for acetylcholinesterase activity (E.C.3.1.1.7. are using toxic inhibitors (BW284c51 and iso-OMPA to distinguish the enzyme from butyrylcholinesterase (E.C.3.1.1.8. which occurs simultaneously in the cerebrospinal fluid. Applying Ellman's colorimetric method, we were looking for a non-toxic inhibitor to restrain butyrylcholinesterase activity. Based on results of previous in vitro studies bupivacaine emerged to be a suitable inhibitor. Results Pharmacokinetic investigations with purified cholinesterases have shown maximum inhibition of butyrylcholinesterase activity and minimal interference with acetylcholinesterase activity at bupivacaine final concentrations between 0.1 and 0.5 mmol/l. Based on detailed analysis of pharmacokinetic data we developed three equations representing enzyme inhibition at bupivacaine concentrations of 0.1, 0.2 and 0.5 mmol/l. These equations allow us to calculate the acetylcholinesterase activity in solutions containing both cholinesterases utilizing the extinction differences measured spectrophotometrically in samples with and without bupivacaine. The accuracy of the bupivacaine-inhibition test could be confirmed by investigations on solutions of both purified cholinesterases and on samples of human cerebrospinal fluid. If butyrylcholinesterase activity has to be assessed simultaneously an independent test using butyrylthiocholine iodide as substrate (final concentration 5 mmol/l has to be conducted. Conclusions The bupivacaine-inhibition test is a reliable method using spectrophotometrical techniques to measure acetylcholinesterase activity in cerebrospinal fluid. It avoids the use of toxic inhibitors for differentiation of acetylcholinesterase from butyrylcholinesterase in fluids containing both enzymes. Our investigations suggest that bupivacaine concentrations of 0.1, 0.2 or 0.5 mmol/l can be applied with the same effect using 1 mmol/l acetylthiocholine iodide as substrate.

  20. Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis

    DEFF Research Database (Denmark)

    Modvig, S; Degn, M; Sander, B;

    2016-01-01

    -L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis. METHODS: We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar......BACKGROUND: Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. OBJECTIVE: The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF...... puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion...

  1. Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-07-01

    Full Text Available The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

  2. Spontaneous cerebrospinal fluid leak following a pilates class: a case report

    OpenAIRE

    Davis, James; Yanny, Irini; Chatu, Sukhdev; Dubois, Patrick; Hayee, Bu; Moran, Nick

    2014-01-01

    Introduction A spinal cerebrospinal fluid leak is the most common cause of spontaneous intracranial hypotension which is an uncommon but increasingly recognized cause of headache. This article describes the first reported case of pilates being associated with a spontaneous spinal cerebrospinal fluid leak whilst also highlighting the key information about spontaneous cerebrospinal fluid leaks that will be useful to the general clinician. Case presentation We present the case of a 42-year-old C...

  3. Oral Fluids that Detect Cardiovascular Disease Biomarkers

    Science.gov (United States)

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R; Kolasa, Justin; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.

    2013-01-01

    Objective To determine the utility of oral fluids for assessment of coronary and cardiovascular (CVD) health. Study Design Twenty-nine patients with pre-existing CVD disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, 48 hr. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than LS and GS. Coronary and CVD disease biomarkers in UWS correlated better with serum than LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis. PMID:22769406

  4. [Cerebrospinal fluid shunts for hydrocephalus and related disorders].

    Science.gov (United States)

    Ito, Masaki; Houkin, Kiyohiro; Saito, Hisayasu; Shimbo, Daisuke; Motegi, Hiroaki; Kawabori, Masahito; Miyamoto, Michiyuki; Yamauchi, Tomohiro

    2012-10-01

    Cerebrospinal fluid (CSF) shunts are commonly employed to treat patients with hydrocephalus. A large number of papers have been published focusing on complications and failures of CSF shunts. However, there appears to be a paucity of knowledge comprehensively covering both common complications and rare ones. In this systematic review, we surveyed articles about surgical complications of CSF shunts as comprehensively as possible. Quantitative analysis was performed to determine the frequency of well-known complications, mortality and revision rates of CSF shunts. Furthermore, rare complications of CSF shunts have also been reviewed.

  5. Viral loads of cerebrospinal fluid in infants with enterovirus meningitis.

    Science.gov (United States)

    Kawashima, Hisashi; Ioi, Hiroaki; Ishii, Chiako; Hasegawa, Yuka; Amaha, Masahiro; Kashiwagi, Yasuyo; Takekuma, Kouji; Hoshika, Akinori; Watanabe, Yasuo

    2008-01-01

    For a better understanding of the role of the viral load, free radicals, and cytokines in viral meningitis, we surveyed cerebrospinal fluid (CSF) obtained from patients below 1 year of age who showed positive for enterovirus. In their first examinations interleukin (IL)-6 and free radicals increased whereas pleocytosis was rarely observed. IL-6 decreased within the short period. Viral loads and free radicals increased simultaneously. IL-6 and free radicals of CSF are helpful for diagnosis and treatment of viral meningitis at an early stage.

  6. CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

    International Nuclear Information System (INIS)

    We analyzed the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin and a decrease in the γ-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, γ-globulin fraction is shown in the myotonic dystrophy. In addition to the abnormality of IQ, EEG, and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy. (author)

  7. [Immunoglobulins in the cerebrospinal fluid and blood in acute neuroinfections].

    Science.gov (United States)

    Dekonenko, E P; Poliakova, T G; Ivanova, L A; Umanskiĭ, K G; Demidova, S A

    1988-01-01

    The authors have examined 42 patients with viral encephalitides and other central nervous system lesions using a complex of clinical and viroimmunological methods of examination. The main emphasis has been laid on measuring immunoglobulins A, M, and G in the blood serum and cerebrospinal fluid. The results have shown marked changes in humoral immunity. The degree of these changes is directly correlated with severity of encephalitis. Investigation into humoral immunity in patients with neuroinfections and other nervous system diseases contributes to the development of differential diagnostic criteria and better understanding of the relationship between severity and outcome of diseases.

  8. Cerebrospinal fluid scintigraphy in traumas to the nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Nikolov, P. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1983-01-01

    The results of cerebrospinal fluid scintigraphy in 48 patients who had undergone trauma to the nervous system were studied. This method has gained rather insufficient acceptance in the diagnosis of this disease, in fact, it was helpful in detecting a high percentage of pathologic changes (80 per cent). Their type and localization structure was as follows: Narrowing of the spinal CSF space in 25 patients and 1 suspective; encephalonasal fistula - 3 patients; blockade of the lateral pathway of the CSF to the brain convexity - 4 patients; pathologic CSF circulation; dilatation of the convex brain cysterns with disturbances at the resorption site - 3 patients; combined spino-encephalic lesion - 1 patient.

  9. Cervical intradural disc herniation and cerebrospinal fluid leak

    Directory of Open Access Journals (Sweden)

    Ritesh Kansal

    2011-01-01

    Full Text Available Cervical intradural disc herniation (IDH is a rare condition and only 25 cases of cervical have been reported. We report a 45-year-old male who presented with sudden onset right lower limb weakness after lifting heavy weight. Magnetic resonance imaging of the cervical spine showed C5/6 disc prolapse with intradural extension. The patient underwent C5/6 discectomy through anterior cervical approach. Postoperatively, the patient improved in stiffness but developed cerebrospinal fluid leak and the leak resolved with multiple lumbar punctures.

  10. Measurement of fluorescent probes concentration ratio in the cerebrospinal fluid for early detection of Alzheimer's disease

    Science.gov (United States)

    Harbater, Osnat; Gannot, Israel

    2014-03-01

    The pathogenic process of Alzheimer's Disease (AD), characterized by amyloid plaques and neurofibrillary tangles in the brain, begins years before the clinical diagnosis. Here, we suggest a novel method which may detect AD up to nine years earlier than current exams, minimally invasive, with minimal risk, pain and side effects. The method is based on previous reports which relate the concentrations of biomarkers in the Cerebrospinal Fluid (CSF) (Aβ and Tau proteins) to the future development of AD in mild cognitive impairment patients. Our method, which uses fluorescence measurements of the relative concentrations of the CSF biomarkers, replaces the lumbar puncture process required for CSF drawing. The process uses a miniature needle coupled trough an optical fiber to a laser source and a detector. The laser radiation excites fluorescent probes which were prior injected and bond to the CSF biomarkers. Using the ratio between the fluorescence intensities emitted from the two biomarkers, which is correlated to their concentration ratio, the patient's risk of developing AD is estimated. A theoretical model was developed and validated using Monte Carlo simulations, demonstrating the relation between fluorescence emission and biomarker concentration. The method was tested using multi-layered tissue phantoms simulating the epidural fat, the CSF in the sub-arachnoid space and the bone. These phantoms were prepared with different scattering and absorption coefficients, thicknesses and fluorescence concentrations in order to simulate variations in human anatomy and in the needle location. The theoretical and in-vitro results are compared and the method's accuracy is discussed.

  11. Low Cerebrospinal Fluid Amyloid-Beta Concentration Is Associated with Poorer Delayed Memory Recall in Women

    Directory of Open Access Journals (Sweden)

    Fanni Haapalinna

    2016-07-01

    Full Text Available Background: Data on the association of memory performance with cerebrospinal fluid (CSF biomarkers of Alzheimer's disease (AD are inconsistent. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NB is a commonly used validated cognitive tool; however, only few studies have examined its relationship with CSF biomarkers for AD. We studied the correlation of pathological changes in CSF biomarkers with various CERAD-NB subtests and total scores. Methods: Out of 79 subjects (36 men, mean age 70.5 years, 63 had undergone an assessment of cognitive status with CERAD-NB and a CSF biomarker analysis due to a suspected memory disorder, and 16 were controls with no memory complaint.Results: In women we found a significant correlation between CSF amyloid-beta (Aβ1-42 and several subtests measuring delayed recall. Word List Recall correlated with all markers: Aβ1-42 (r = 0.323, p = 0.035, tau (r = -0.304, p = 0.050 and hyperphosphorylated tau (r = -0.331, p = 0.046. No such correlations were found in men. Conclusions: CSF biomarkers correlate with delayed memory scores in CERAD-NB in women, and women may have more actual AD pathology at the time of the investigations than men.

  12. Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease.

    Science.gov (United States)

    Zhang, Jing; Mattison, Hayley A; Liu, Changqin; Ginghina, Carmen; Auinger, Peggy; McDermott, Michael P; Stewart, Tessandra; Kang, Un Jung; Cain, Kevin C; Shi, Min

    2013-11-01

    Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1-42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total

  13. AUTOMATIC TURBIDIMETRY IN DETECTING PROTEIN IN URINE AND CEREBROSPINAL FLUID

    Institute of Scientific and Technical Information of China (English)

    张建荣; 李闻捷; 徐德安

    2002-01-01

    Objective To evaluate and validate the performance of automatic turbidimetry in detecting protein in urine and cerebrospinal fluid.Methods The detection limits, reportable range of results, precision and accuracy of the method were investigated by using the Roche chemical reagent, benzethonium chloride.Results The functional sensitivity was 0.08g/L of protein, the reportable range of result was between 0.08g/L and 2.0g/L; the intra-batch coefficient of variation(CV) was 1.5% and the inter-batch CV was 2.2%, and the regression relation between new method and routine SSA method in patient sample determination was Y1 = 0.86X+0.068, r=0.972 and Y2=0.86X+0.056, r=0.980 for urine and cerebrospinal fluid respectively.Conclusion This method is simple, accurate, time saving with minimal sample volume 5~15μl, and suitalbe for clinical practice.

  14. Evaluation of the Production and Absorption of Cerebrospinal Fluid.

    Science.gov (United States)

    Miyajima, Masakazu; Arai, Hajime

    2015-01-01

    The traditional hypothesis of cerebrospinal fluid (CSF) hydrodynamics presumes that CSF is primarily produced in the choroid plexus (CP), then flows from the ventricles into the subarachnoid spaces, and mainly reabsorbed in the arachnoid granulations. This hypothesis is necessary to reconsider in view of recent research and clinical observations. This literature review presents numerous evidence for a new hypothesis of CSF hydrodynamics-(1) A significantly strong relationship exists between the CSF and interstitial fluid (IF), (2) CSF and IF are mainly produced and absorbed in the parenchymal capillaries of the brain and spinal cord. A considerable amount of CSF and IF are also absorbed by the lymphatic system, and (3) CSF movement is not unidirectional flow. It is only local mixing and diffusion. PMID:26226980

  15. Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

    Science.gov (United States)

    Linninger, Andreas A.; Tangen, Kevin; Hsu, Chih-Yang; Frim, David

    2016-01-01

    Cerebrospinal fluid (CSF) is not stagnant but displays fascinating oscillatory flow patterns inside the ventricular system and reversing fluid exchange between the cranial vault and spinal compartment. This review provides an overview of the current knowledge of pulsatile CSF motion. Observations contradicting classical views about its bulk production and clearance are highlighted. A clinical account of diseases of abnormal CSF flow dynamics, including hydrocephalus, syringomyelia, Chiari malformation type 1, and pseudotumor cerebri, is also given. We survey medical imaging modalities used to observe intracranial dynamics in vivo. Additionally, we assess the state of the art in predictive models of CSF dynamics. The discussion addresses open questions regarding CSF dynamics as they relate to the understanding and management of diseases.

  16. Antifungal activity in human cerebrospinal fluid and plasma after intravenous administration of Allium sativum.

    OpenAIRE

    Davis, L E; Shen, J K; Cai, Y.

    1990-01-01

    Commercial Allium sativum (garlic) extract was given intravenously to two patients with cryptococcal meningitis and three patients with other types of meningitis. Plasma titers of anti-Cryptococcus neoformans activity rose twofold over preinfusion titers. Anti-C. neoformans activity was detected in four of five cerebrospinal fluid samples but not in pooled normal cerebrospinal fluid.

  17. MANAGEMENT OF CEREBROSPINAL FLUID LEAKAGE FOLLOWING CERVICAL SPINE SURGERY

    Institute of Scientific and Technical Information of China (English)

    Ye Tian; Ke-yi Yu; Yi-peng Wang; Jun Qian; Gui-xing Qiu

    2008-01-01

    Objective To investigate the management and outcome of cerebrospinal fluid leakage (CSFL) after cervical surgery. Methods Medical records of 642 patients who underwent cervical surgery between December 1999 and December 2005 at our hospital were retrospectively reviewed. Five patients complicated by CSFL after surgery were enrolled, of which 4 cases were complicated after ossified posterior longitudinal ligament or posterior vertebral osteophyte resection directly injuring the dura, and 1 case after posterior cervical double-door laminoplasty with out observed dural injury during surgery. Of the 5 CSFL cases, 4 cases occurred at 1-3 days after operation and 1 case at 9 days after operation. All 5 postoperative CSFL cases were treated through wound drainage removal, wound sutures, prophylactic antibiotics, and continuous subarachnoid drainage in the elevated head position.Results All 5 CSFL cases experienced leakage cessation within 1-3 days and wound healing within 4-8 days, and subarachnoid drainage lasted 11-16 days with an average volume of 320 mL (range, 150-410 mL). Four cases experienced headache, nausea and vomiting, 1 case suffered from somnolence and hyponatremia, and symptoms subsided after symptomatic treatment and intravenous fluid administration. All patients were followed up for an average of 32 months (range, 22-50 months). No occurrence of cerebrospinal fluid cyst or wound infection was observed. CSFL produced no significant negative effects upon neuromuscular function recovery.Conclusion Continuous subarachnoid cavity drainage in combination with elevated head position is a simple and safe non-surgical method in treatment of CSFL following cervical surgery.

  18. Arachnoid granulations may control heat exchange between intracranial dural sinuses and cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Abdullah Kaya

    2013-02-01

    Full Text Available Selective brain cooling is a system in a human that protects the brain from hyperthermia. Cool venous blood from head skin and upper respiratory tract drains into intracranial dural sinuses. In that region, cool blood in the dural sinuses decreases the temperature of the cerebrospinal fluid. Cerebrospinal fluid provides brain cooling. All cortical arteries to the brain pass the cerebrospinal fluid compartment. Also cerebrospinal fluid washes cortical nervous tissue. To provide optimal temperature for the brain cortex, heat exchange between cerebrospinal fluid and venous blood in dural sinuses should be well controlled. Head skin is in direct contact with the outside, and significant heat exchanges may occur within dural sinuses. A barrier made of dura mater and arachnoid mater has been proposed to transmit heat from dural sinuses to the cerebrospinal fluid. However, this barrier is a mechanical barrier and can’t optimize the temperature of cerebrospinal fluid. Also it has two laminas (dura mater and arachnoid mater and dura mater has a high vascularization. Therefore, this barrier may obstruct heat exchange. In this hypothetical paper, I offer arachnoid granulations as a functional barrier for heat exchange between blood in dural sinuses and cerebrospinal fluid. Arachnoid granulations are invaginations of arachnoid mater to the dural sinuses. Cerebrospinal fluid passes to the dural sinuses via arachnoid granulations. An arachnoid granulation provides a very thin wall between two compartments and may transmit heat effectively. Also arachnoid granulations may control cerebrospinal fluid flow to the dural sinuses according to temperature differences between two compartments. It is worth researching whether there are any functional or histological differences of the arachnoid granulations between people living in cold and hot places. There may also be an association between pathologies such as migraine and pseudotumor cerebri and this possible

  19. A quantitative analysis of cerebrospinal fluid flow in posttraumatic syringomyelia

    International Nuclear Information System (INIS)

    Cerebrospinal fluid (CSF) flow within the spinal canal and syrinx in posttraumatic syringomyelia were studied by cardiac-gated phase images of magnetic resonance imaging in 12 normal volunteers and 8 patients with syringomyelia. The cardiac-gated phase method was simple and useful for detection of CSF flow. Phase modulation was in direct proportion to flow velocity. Phase modulation was not affected by the T1 or T2 relaxation time. In normal volunteers, CSF flows caudally during systole and cranially during diastole. The maximum caudal CSF flow velocity at C2 level was from 0.45 cm/sec to 1.71 cm/sec, average; 1.27 cm/sec. All of symptomatic posttraumatic syringomyelia patients had the flow in the syrinx. (author)

  20. Massive Cerebrospinal Fluid Leak of the Temporal Bone

    Directory of Open Access Journals (Sweden)

    Giannicola Iannella

    2016-01-01

    Full Text Available Cerebrospinal fluid (CSF leakage of the temporal bone region is defined as abnormal communications between the subarachnoidal space and the air-containing spaces of the temporal bone. CSF leak remains one of the most frequent complications after VS surgery. Radiotherapy is considered a predisposing factor for development of temporal bone CSF leak because it may impair dural repair mechanisms, thus causing inadequate dural sealing. The authors describe the case of a 47-year-old man with a massive effusion of CSF which extended from the posterior and lateral skull base to the first cervical vertebrae; this complication appeared after a partial enucleation of a vestibular schwannoma (VS with subsequent radiation treatment and second operation with total VS resection.

  1. Cerebrospinal fluid carnitine levels in patients with Alzheimer's disease.

    Science.gov (United States)

    Rubio, J C; de Bustos, F; Molina, J A; Jiménez-Jiménez, F J; Benito-León, J; Martín, M A; Campos, Y; Ortí-Pareja, M; Cabrera-Valdivia, F; Arenas, J

    1998-03-01

    We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no significant correlation between FC and AC levels in CSF. FC and AC levels in CSF did not differ significantly between AD patients and controls, but plasma FC levels were significantly lower in AD patients. CSF and plasma FC and AC levels did not correlate with age, age at onset of AD, duration of AD, and scores of the Minimental State Examination of Folstein. Although these results suggest that CSF carnitine levels are apparently unrelated with the risk for AD, the trend of the FC/AC ratio to be higher in AD patients might suggest the possibility of a lower carnitine acetyltransferase activity in AD, as previously reported in some brain areas. PMID:9562266

  2. Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease.

    Science.gov (United States)

    Rodrigues, Filipe Brogueira; Byrne, Lauren; McColgan, Peter; Robertson, Nicola; Tabrizi, Sarah J; Leavitt, Blair R; Zetterberg, Henrik; Wild, Edward J

    2016-10-01

    Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre-symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale '99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme-linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p international pilot study. Age-adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p = 0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r = -0.29, p = 0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r = 0.32, p = 0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age-adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of neuronal death, in cerebrospinal fluid and found it was increased in patients with

  3. Altered cerebrospinal fluid proteins in Smith-Lemli-Opitz syndrome patients.

    Science.gov (United States)

    Cologna, Stephanie M; Shieh, Christine; Toth, Cynthia L; Cougnoux, Antony; Burkert, Kathryn R; Bianconi, Simona E; Wassif, Christopher A; Porter, Forbes D

    2016-08-01

    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple malformation syndrome with neurocognitive impairment. SLOS arises from mutations in the 7-dehydrocholesterol reductase gene which results in impaired enzymatic conversion of 7-dehydrocholesterol to cholesterol. In the current work, we sought to measure proteins that were altered in the cerebrospinal fluid from SLOS patients compared to pediatric controls. Using a multi-analyte antibody-based assay, we found that 12 proteins are altered in SLOS patients. Validation studies were carried out and the findings from this study suggest alterations in extracellular matrix remodeling and further evidence of oxidative stress within the disease pathophysiology. The results of this study will be used to explore biological pathways altered in SLOS and identifies a set of CSF proteins that can be evaluated as biomarkers in future therapeutic trials. © 2016 Wiley Periodicals, Inc. PMID:27148958

  4. Idiopathic cerebrospinal fluid overproduction: case-based review of the pathophysiological mechanism implied in the cerebrospinal fluid production.

    Science.gov (United States)

    Trevisi, Gianluca; Frassanito, Paolo; Di Rocco, Concezio

    2014-08-28

    Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications. PMID:25165051

  5. Cerebrospinal fluid biomarkers for early diagnosis of Alzheimer disease%阿尔茨海默病患者的脑脊液tau蛋白及Aβ1-42水平

    Institute of Scientific and Technical Information of China (English)

    单守勤; 赵权; 张立营; 孙英姿

    2011-01-01

    目的 探讨脑脊液(cerebrospinal fluid,CSF)中tau蛋白及β-淀粉样蛋白1-42(Aβ1-42)对诊断阿尔茨海默病(Alzheimer's disease,AD)的早期诊断价值,寻找AD理想的生物学标志.方法 采用酶联免疫吸附法检测36例AD、24例血管性痴呆患者(vascular dementia,VD)和26名正常对照者(对照组)CSF中tau蛋白及Aβ1-42浓度的变化.结果 CSF中tau蛋白平均浓度:AD组(336±126)ng/L,VD组(183±96)ng/L,对照组(98±54)ng/L,AD组CSF中tau蛋白浓度明显高于对照组,差异有统计学意义(P<0.05);CSF中Aβ1-42平均浓度:AD组(341β113)ng/L,VD组(457±132)ng/L,对照组(502±167)ng/L,AD组CSF中Aβ1-42浓度明显低于对照组.差异有显著性意义(P<0.05).结论 脑脊液Aβ1-42、tau蛋白浓度的变化,不仅对诊断阿尔茨海默病具有较高的敏感性和特异性,而且亦可作为阿尔茨海默病与血管性痴呆鉴别诊断的生物学指标.%Objective To investigate the relationship between impaired hippocampal neurogenesis and altered Notchl signaling in depressed rats. Methods In the present study, chronic unpredictable mild stress (CUMS) was used to inhibit the neurogenesis in the hippocampus. The function of Notchl signaling was investigated by using realtime PCR and western blot at different time points (14 d and 28 d) during chronic stress. The hippocampal neurogenesis was monitored by assessing cell proliferation, survival, and differentiation. Results After 14 days, CUMS significantly reduced weight (P < 0.05), the sucrose preference (P < 0.001), number of squares crossed (P < 0.01) and number of grooming and rearing compared with the controls. The immobility time was significantly increased after 14 d CUMS treated relative to the controls (P < 0.001). Twenty-eight days after CUMS protocol, these parameters were significantly difference in rats exposed to CUMS compare with the controls (weight, P < 0.05; sucrose preference, P < 0.001; number of squares crossed, P< 0.001; number of

  6. Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid.

    Science.gov (United States)

    Martin, C; Alonso, M I; Santiago, C; Moro, J A; De la Mano, A; Carretero, R; Gato, A

    2009-11-01

    Cerebrospinal fluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinal fluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinal fluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinal fluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinal fluid, we show that the neuroepithelium needs the trophic influence of cerebrospinal fluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinal fluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates. PMID:19540909

  7. Proteomic analysis of cerebrospinal fluid in California sea lions (Zalophus californianus) with domoic acid toxicosis identifies proteins associated with neurodegeneration.

    Science.gov (United States)

    Neely, Benjamin A; Soper, Jennifer L; Gulland, Frances M D; Bell, P Darwin; Kindy, Mark; Arthur, John M; Janech, Michael G

    2015-12-01

    Proteomic studies including marine mammals are rare, largely due to the lack of fully sequenced genomes. This has hampered the application of these techniques toward biomarker discovery efforts for monitoring of health and disease in these animals. We conducted a pilot label-free LC-MS/MS study to profile and compare the cerebrospinal fluid from California sea lions with domoic acid toxicosis (DAT) and without DAT. Across 11 samples, a total of 206 proteins were identified (FDRlions with DAT: complement C3, complement factor B, dickkopf-3, malate dehydrogenase 1, neuron cell adhesion molecule 1, gelsolin, and neuronal cell adhesion molecule. Immunoblot analysis found reelin to be depressed in the cerebrospinal fluid from California sea lions with DAT. Mice administered domoic acid also had lower hippocampal reelin protein levels suggesting that domoic acid depresses reelin similar to kainic acid. In summary, proteomic analysis of cerebrospinal fluid in marine mammals is a useful tool to characterize the underlying molecular pathology of neurodegenerative disease. All MS data have been deposited in the ProteomeXchange with identifier PXD002105 (http://proteomecentral.proteomexchange.org/dataset/PXD002105).

  8. Dynamic oxygen-enhanced MRI of cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Taha M Mehemed

    Full Text Available Oxygen causes an increase in the longitudinal relaxation rate of tissues through its T1-shortening effect owing to its paramagnetic properties. Due to such effects, MRI has been used to study oxygen-related signal intensity changes in various body parts including cerebrospinal fluid (CSF space. Oxygen enhancement of CSF has been mainly studied using MRI sequences with relatively longer time resolution such as FLAIR, and T1 value calculation. In this study, fifteen healthy volunteers were scanned using fast advanced spin echo MRI sequence with and without inversion recovery pulse in order to dynamically track oxygen enhancement of CSF. We also focused on the differences of oxygen enhancement at sulcal and ventricular CSF. Our results revealed that CSF signal after administration of oxygen shows rapid signal increase in both sulcal CSF and ventricular CSF on both sequences, with statistically significant predominant increase in sulcal CSF compared with ventricular CSF. CSF is traditionally thought to mainly form from the choroid plexus in the ventricles and is absorbed at the arachnoid villi, however, it is also believed that cerebral arterioles contribute to the production and absorption of CSF, and controversy remains in terms of the precise mechanism. Our results demonstrated rapid oxygen enhancement in sulcal CSF, which may suggest inhaled oxygen may diffuse into sulcal CSF space rapidly probably due to the abundance of pial arterioles on the brain sulci.

  9. Cerebrospinal fluid folate and cobalamin levels in febrile convulsion.

    Science.gov (United States)

    Osifo, B O; Lukanmbi, F A; Familusi, J B

    1985-05-01

    Folate and cobalamin parameters were studied in the serum and cerebrospinal fluid of 40 febrile paediatric patients. Eighteen of these children were in a state of febrile convulsion while the remaining 22 were non-convulsing. The serum folate concentration of all the patients was higher than that of the control group but the highest value was found in the convulsing children. There was no significant difference in the CSF folate levels between the two groups of patients. The serum cobalamin levels of the patients were significantly lower than those of the control children and the lowest mean was observed in the convulsing state. On the other hand, there was no difference in the CSF cobalamin between the convulsing and non-convulsing children. These results confirm that there is an effective blood-brain barrier system for folate even when serum folate levels are higher than normal. There is also a definite decrease in serum cobalamin during pyrexia but this decrease is more apparent in the convulsing state. The role of cobalamin metabolism in convulsion is not clear. PMID:4009203

  10. Cerebrospinal fluid neopterin and cryopyrin-associated periodic syndrome.

    Science.gov (United States)

    Serrano, Mercedes; Ormazábal, Aida; Antón, Jordi; Aróstegui, Juan I; García-Cazorla, Angels

    2009-12-01

    Cryopyrin-associated periodic syndrome is a category of autoinflammatory disorders caused by mutations of the NLRP3 gene, with chronic infantile neurologic cutaneous and articular syndrome being the severest clinical phenotype. Various pterins have been reported as mediating immunologic functions in the central nervous system, but to date studies of pterin cerebrospinal fluid (CSF) values and cryopyrin-associated periodic syndrome have been lacking. A 2-year-old child was affected with a severe atypical form of cryopyrin-associated periodic syndrome, suspected based on the analysis of neopterin in CSF. He initially presented isolated neurologic manifestations mimicking a neuroregressive disorder. Blood and CSF analyses did not present any routine inflammatory markers, but CSF neopterin was elevated. Later, the patient developed arthritis and recurrent episodes of fever, and the cryopyrin-associated periodic syndrome diagnosis was confirmed by genetic studies. Neopterin was the most altered indicator over the time. Child neurologists should be on the alert when unexplained neurologic signs appear, giving consideration to the possibility of inflammatory or immune-mediated diseases. The present case demonstrates the clinical utility of measurement of CSF neopterin levels in screening for these immune-mediated diseases, especially when neurologic symptoms are associated with normal results on routine CSF tests.

  11. Vitamin B6 in plasma and cerebrospinal fluid of children.

    Directory of Open Access Journals (Sweden)

    Monique Albersen

    Full Text Available Over the past years, the essential role of vitamin B6 in brain development and functioning has been recognized and genetic metabolic disorders resulting in functional vitamin B6 deficiency have been identified. However, data on B6 vitamers in children are scarce.B6 vitamer concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF of 70 children with intellectual disability were determined by ultra performance liquid chromatography-tandem mass spectrometry. For ethical reasons, CSF samples could not be obtained from healthy children. The influence of sex, age, epilepsy and treatment with anti-epileptic drugs, were investigated.The B6 vitamer composition of plasma (pyridoxal phosphate (PLP > pyridoxic acid > pyridoxal (PL differed from that of CSF (PL > PLP > pyridoxic acid > pyridoxamine. Strong correlations were found for B6 vitamers in and between plasma and CSF. Treatment with anti-epileptic drugs resulted in decreased concentrations of PL and PLP in CSF.We provide concentrations of all B6 vitamers in plasma and CSF of children with intellectual disability (±epilepsy, which can be used in the investigation of known and novel disorders associated with vitamin B6 metabolism as well as in monitoring of the biochemical effects of treatment with vitamin B6.

  12. Simulating transitional hydrodynamics of the cerebrospinal fluid at extreme scale

    Science.gov (United States)

    Jain, Kartik; Roller, Sabine; Mardal, Kent-Andre

    Chiari malformation type I is a disorder characterized by the herniation of cerebellar tonsils into the spinal canal through the foramen magnum resulting in obstruction to cerebrospinal fluid (CSF) outflow. The flow of pulsating bidirectional CSF is of acutely complex nature due to the anatomy of the conduit containing it - the subarachnoid space. We report lattice Boltzmann method based direct numerical simulations on patient specific cases with spatial resolution of 24 μm amounting meshes of up to 2 billion cells conducted on 50000 cores of the Hazelhen supercomputer in Stuttgart. The goal is to characterize intricate dynamics of the CSF at resolutions that are of the order of Kolmogorov microscales. Results unfold velocity fluctuations up to ~ 10 KHz , turbulent kinetic energy ~ 2 times of the mean flow energy in Chiari patients whereas the flow remains laminar in a control subject. The fluctuations confine near the cranio-vertebral junction and are commensurate with the extremeness of pathology and the extent of herniation. The results advocate that the manifestation of pathological conditions like Chiari malformation may lead to transitional hydrodynamics of the CSF, and a prudent calibration of numerical approach is necessary to avoid overlook of such phenomena.

  13. Cerebrospinal fluid ferritin in children with viral and bacterial meningitis.

    Science.gov (United States)

    Rezaei, M; Mamishi, S; Mahmoudi, S; Pourakbari, B; Khotaei, G; Daneshjou, K; Hashemi, N

    2013-01-01

    Despite the fact that the prognosis of bacterial meningitis has been improved by the influence of antibiotics, this disease is still one of the significant causes of morbidity and mortality in children. Rapid differentiation between bacterial and aseptic meningitis, and the need for immediate antibiotic treatment in the former, is crucial in the prognosis of these patients. Ferritin is one of the most sensitive biochemical markers investigated in cerebrospinal fluid (CSF) for the early diagnosis of bacterial meningitis. The present study aims to evaluate the diagnostic capability of CSF ferritin in differentiating bacterial and viral meningitis in the paediatric setting. A cross-sectional study was carried out in the referral Children's Medical Center Hospital, Tehran, during 2008 and 2009. According to the inclusion criteria, CSF samples from 42 patients with suspected meningitis were obtained and divided into two meningitis groups, bacterial (n = 18) and viral (n = 24). Ferritin and other routine determinants (i.e., leucocytes, protein and glucose) were compared between the two groups. Ferritin concentration in the bacterial meningitis group was 106.39 +/- 86.96 ng/dL, which was considerably higher than in the viral meningitis group (10.17 +/- 14.09, P meningitis group and showed a positive correlation with CSF ferritin. In conclusion, this study suggests that CSF ferritin concentration is an accurate test for the early differentiation of bacterial and aseptic meningitis; however, further investigation on a larger cohort of patients is required to confirm this finding.

  14. Embryonic cerebrospinal fluid in brain development: neural progenitor control.

    Science.gov (United States)

    Gato, Angel; Alonso, M Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M F; Lamus, Francisco; Desmond, Mary E

    2014-08-28

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called "embryonic CSF." Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. PMID:25165044

  15. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    Energy Technology Data Exchange (ETDEWEB)

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  16. Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

    Science.gov (United States)

    Kumpulainen, Elina; Välitalo, Pyry; Kokki, Merja; Lehtonen, Marko; Hooker, Andrew; Ranta, Veli-Pekka; Kokki, Hannu

    2010-01-01

    AIMS This study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen. METHODS The pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n = 27) or by mouth as syrup (n = 37). A single cerebrospinal fluid (CSF) sample (n = 60) was collected at the induction of anaesthesia, and plasma samples (n = 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package. RESULTS Flurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96 l h−1 70 kg−1. Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (Vss) was 8.1 l 70 kg−1. Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations. CONCLUSIONS Flurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6 months, while more research is needed in neonates and in younger infants. PMID:20840447

  17. Gamma-aminobutyric acid (GABA in cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Kuroda,Hiroo

    1983-06-01

    Full Text Available Levels of gamma-aminobutyric acid (GABA in cerebrospinal fluid (CSF were measured by radioreceptor assay (RRA in 25 normal controls and in 121 patients with various central nervous system disorders. CSF-GABA levels could be measured down to 5 pmoles/ml reliably by this assay. In normal controls, the mean (+/- SEM GABA level in CSF was 127 +/- 5.2 pmoles/ml. There was no correlation between age, sex and the CSF-GABA level in normal controls. The lowest CSF-GABA level, which was 60 +/- 6.0 pmoles/ml, was observed in alcoholic patients suffering from cerebellar ataxia. The CSF-GABA levels were quite low in patients with Alzheimer's disease, late cortical cerebellar atrophy, neuro-Behcet's syndrome, olivopontocerebellar atrophy, Huntington's chorea, Parkinson's disease and cerebral hemorrhage. On the other hand, the CSF-GABA levels of meningitis patients were significantly increased. These findings suggest that measuring the CSF-GABA level is quite beneficial in the diagnosis and pathophysiological determinations of some diseases.

  18. Virtual MRI endoscopy of the intracranial cerebrospinal fluid spaces

    Energy Technology Data Exchange (ETDEWEB)

    Shigematsu, Y.; Korogi, Y.; Hirai, T. [Kumamoto Univ. (Japan). Dept. of Radiology; Okuda, T.; Ikushima, I.; Sugahara, T.; Liang, L.; Ge, Y.; Takahashi, M.

    1998-10-01

    We used constructive interference in steady state (CISS) 3D Fourier transform (3DFT) MRI data sets to obtain three-dimensional (3D) virtual MRI endoscopic views of the intracranial cerebrospinal fluid (CSF) spaces, processing them with a commercially available perspective endoscopic algorithm. We investigated the potential of the intracranial virtual MRI endoscopy applied to visualisation of the pathology in 13 patients with surgically confirmed trigeminal neuralgia (3), hemifacial spasm (3), acoustic neuroma (3), suprasellar germinoma (1), Langerhans cell histiocytosis (1), lateral ventricle nodules (1) and pituitary dwarfism (1). All images were acquired using a 1.5-T imager employing a circular polarised head coil. The CISS-3DFT data sets were transferred to a workstation for processing with the perspective endoscopic algorithm. Postprocessing for virtual MRI endoscopy was possible for all data sets. The lesions in 12 patients, and their complex anatomical relationships with the surrounding structures, were well seen on the 3D images. A small acoustic neuroma in the internal auditory meatus was not seen using virtual endoscopy. Although virtual MRI endoscopy has limitations, it provides 3D images which cannot be acquired using any other procedure. (orig.) With 6 figs., 16 refs.

  19. Phantom model of physiologic intracranial pressure and cerebrospinal fluid dynamics.

    Science.gov (United States)

    Bottan, Simone; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2012-06-01

    We describe herein a novel life-size phantom model of the intracranial cavity and its validation. The cerebrospinal fluid (CSF) domains including ventricular, cysternal, and subarachnoid spaces were derived via magnetic resonance imaging. Brain mechanical properties and cranio-spinal compliance were set based on published data. Both bulk and pulsatile physiologic CSF flow were modeled. Model validation was carried out by comparisons of flow and pressure measurements in the phantom with published in vivo data of healthy subjects. Physiologic intracranial pressure with 10 mmHg mean and 0.4 mmHg peak pulse amplitude was recorded in the ventricles. Peak CSF flow rates of 0.2 and 2 ml/s were measured in the cerebral aqueduct and subarachnoid space, respectively. The phantom constitutes a first-of-its-kind approach to modeling physiologic intracranial dynamics in vitro. Herein, we describe the phantom design and manufacturing, definition and implementation of its operating parameters, as well as the validation of the modeled dynamics. PMID:22333981

  20. Head movement, an important contributor to human cerebrospinal fluid circulation

    Science.gov (United States)

    Xu, Qiang; Yu, Sheng-Bo; Zheng, Nan; Yuan, Xiao-Ying; Chi, Yan-Yan; Liu, Cong; Wang, Xue-Mei; Lin, Xiang-Tao; Sui, Hong-Jin

    2016-01-01

    The suboccipital muscles are connected to the upper cervical spinal dura mater via the myodural bridges (MDBs). Recently, it was suggested that they might work as a pump to provide power for cerebrospinal fluid (CSF) circulation. The purpose of this study was to investigate effects of the suboccipital muscles contractions on the CSF flow. Forty healthy adult volunteers were subjected to cine phase-contrast MR imaging. Each volunteer was scanned twice, once before and once after one-minute-head-rotation period. CSF flow waveform parameters at craniocervical junction were analyzed. The results showed that, after the head rotations, the maximum and average CSF flow rates during ventricular diastole were significantly increased, and the CSF stroke volumes during diastole and during entire cardiac cycle were significantly increased. This suggested that the CSF flow was significantly promoted by head movements. Among the muscles related with head movements, only three suboccipital muscles are connected to the upper cervical spinal dura mater via MDBs. It was believed that MDBs might transform powers of the muscles to CSF. The present results suggested that the head movements served as an important contributor to CSF dynamics and the MDBs might be involved in this mechanism. PMID:27538827

  1. Cerebrospinal Fluid Markers in Sporadic Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    Andrea Galassi

    2011-09-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG, and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF. In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP, a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated181 tau, and amyloid beta (Aβ peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most sensitive indicators of sCJD, the highest sensitivity, specificity and positive predictive value were obtained when all the above markers were combined. The latter approach also allowed a reliable differential diagnosis with other neurodegenerative dementias.

  2. Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis

    Directory of Open Access Journals (Sweden)

    Erdal Taskın

    2004-01-01

    Full Text Available Aims: To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis.

  3. Procollagen I C-propeptide in the cerebrospinal fluid of neonates with posthaemorrhagic hydrocephalus

    OpenAIRE

    Heep, A; Stoffel-Wagner, B.; Soditt, V; Aring, C; Groneck, P; Bartmann, P.

    2002-01-01

    Background: The pathogenesis of posthaemorrhagic hydrocephalus (PHHC) following intraventricular haemorrhage (IVH) in premature infants includes a fibroproliferative reaction leading to arachnoidal fibrosis, ultimately causing malresorption of cerebrospinal fluid (CSF) at the arachnoid villi.

  4. [Nitroblue tetrazolium reduction by the neutrophils of the cerebrospinal fluid and peripheral blood and by the monocytic-reticular cells of the cerebrospinal fluid in neuroinfections].

    Science.gov (United States)

    Kucharska-Demczuk, K

    1980-01-01

    Using the method of Park et al. the author studied spontaneous and stimulated NBT reduction by neutrophil granulocytes in the cerebrospinal fluid and blood, and by monocytic-reticular cells in the cerebrospinal fluid of the patients with bacterial and viral meningitis and meningismus. The author performed 333 investigations in 74 patients. Significantly higher mean values of the index of spontaneous and stimulated NBT reduction by the granulocytes and cerebrospinal fluid were observed in cases of bacterial meningitis as compared with the granulocytes of the peripheral blood in healthy subjects. It was demonstrated that in patients with bacterial meningitis blood and fluid granulocytes showed a similar phagocytic acitivty independent of the humoral environment. In the patients with bacterial and viral meningitis the monocytic-reticular cells the cerebrospinal fluid showed a similar, sometimes high, phagocytic activity depending on the phase and severity of the disease. On the otherhand, in most cases of meningismus these cells failed to manifest any phagocytic and bactericidal activity. In only few isolated cells in the fluid weak NBT reduction was observed. The obtained results of investigations showed the usefulness of the NBT test not only for the differential diagnosis of the aetiology of neuroinfections but also for the assessment of immune processes taking place in the nervous system.

  5. Regional cortical thinning and cerebrospinal biomarkers predict worsening daily functioning across the Alzheimer disease spectrum

    Science.gov (United States)

    Marshall, Gad A.; Lorius, Natacha; Locascio, Joseph J.; Hyman, Bradley T.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2014-01-01

    Background Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer's Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (p<0.0001), greater lateral occipital cortical thickness and diagnosis (p<0.0001), and greater amyloid-beta 1-42 (Aβ1-42) and diagnosis (p=0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p=0.02) and inferior temporal (p=0.05) cortical thickness, lower Aβ1-42 (p<0.0001), and greater total tau (t-tau) (p=0.02) were associated with greater rate of IADL impairment over time. Conclusions Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF Aβ1-42, and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI. PMID:24685624

  6. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course

    DEFF Research Database (Denmark)

    Khademi, Mohsen; Kockum, Ingrid; Andersson, Magnus L;

    2011-01-01

    Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments.......Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments....

  7. Subarachnoid Hemorrhage Presenting with Seizure due to Cerebrospinal Fluid Leakage after Spinal Surgery.

    Science.gov (United States)

    Bozkurt, Gokhan; Yaman, Mesut Emre

    2016-01-01

    Cerebrospinal fluid leakage may commonly occur during spinal surgeries and it may cause dural tears. These tears may result in hemorrhage in the entire compartments of the brain. Most common site of such hemorrhages are the veins in the cerebellar region. We report a case of hemorrhage, mimicking aneurysmal subarachnoid hemorrhage due to a cerebrospinal fluid leakage following lumbar spinal surgery and discuss the possible mechanisms of action.

  8. Detection of free endotoxin in cerebrospinal fluid by the Limulus lysate test.

    OpenAIRE

    Munford, R S; Hall, C L; Grimm, L.

    1984-01-01

    We used a rabbit model of Escherichia coli meningitis to study the basis for positive Limulus lysate tests in infected cerebrospinal fluid. The results indicated that positive Limulus tests are due to endotoxins in cerebrospinal fluid and not to leukocyte proteases or other possible activators of the Limulus clotting system. The results also suggest that bacteria-free endotoxin may be present in localized gram-negative bacterial infections.

  9. Normal permeability of blood-cerebrospinal fluid barrier to phosphorus 32

    International Nuclear Information System (INIS)

    The permeability of blood-cerebrospinal fluid barrier (BCSFB) to 32P-inorganic phosphate in sixty five carefully selected individuals free of any organic diseases is studied. The lowest permeability of BCSFB to phosphorus 32 is 0.5 per cent and the highest - 5.0 per cent. Apparently these values are closest to the real fluctuations of normal permeability of BCSFB to the radioactive isotope under study. No sex and age related difference in BCSFB permeability is established, regardless of the fact that the mean permeability of BCSFB to phosphorus 32 after the 50th year of life is 0.6 per cent lower than that in the age 1 to 49 years, the difference is statistically unreliable (p>0.05). A good correlative dependence is established between the concentration of cerebrospinal fluid protein and phosphorus 32 penetration in the cerebrospinal fluid (r = 0.621) which dependence is absent in the organic diseases of the nervous system. No correlative dependence is found between penetration of phosphorus 32 within the cerebrospinal fluid and concentration of cerebrospinal fluid sugar, chlorides and number of cells. In some morbide condition a correlative dependence may occur between permeability of BCSFB to phosphorus 32 and the number of cerebrospinal fluid white cells. (author)

  10. Data for a comprehensive map and functional annotation of the human cerebrospinal fluid proteome

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2015-06-01

    Full Text Available Knowledge about the normal human cerebrospinal fluid (CSF proteome serves as a baseline reference for CSF biomarker discovery and provides insight into CSF physiology. In this study, high-pH reverse-phase liquid chromatography (hp-RPLC was first integrated with a TripleTOF 5600 mass spectrometer to comprehensively profile the normal CSF proteome. A total of 49,836 unique peptides and 3256 non-redundant proteins were identified. To obtain high-confidence results, 2513 proteins with at least 2 unique peptides were further selected as bona fide CSF proteins. Nearly 30% of the identified CSF proteins have not been previously reported in the normal CSF proteome. More than 25% of the CSF proteins were components of CNS cell microenvironments, and network analyses indicated their roles in the pathogenesis of neurological diseases. The top canonical pathway in which the CSF proteins participated was axon guidance signaling. More than one-third of the CSF proteins (788 proteins were related to neurological diseases, and these proteins constitute potential CSF biomarker candidates. The mapping results can be freely downloaded at http://122.70.220.102:8088/csf/, which can be used to navigate the CSF proteome. For more information about the data, please refer to the related original article [1], which has been recently accepted by Journal of Proteomics.

  11. Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Alfred N Fonteh

    Full Text Available Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but

  12. Cerebrospinal fluid dynamics in Chiari malformation associated with syringomyelia

    Institute of Scientific and Technical Information of China (English)

    LIU Bin; WANG Zhen-yu; XIE Jing-cheng; HAN Hong-bin; PEI Xin-long

    2007-01-01

    Background About 50%-70% of patients with Chiari malformation I (CMI) presented with syringomyelia (SM), which is supposed to be related to abnormal cerebrospinal fluid (CSF) flow around the foramen magnum. The aim of this study was to investigate the cerebrospinal fluid dynamics at levels of the aqueduct and upper cervical spine in patients with CMI associated with SM, and to discuss the possible mechanism of formation of SM.Methods From January to April 2004, we examined 10 adult patients with symptomatic CMI associated with SM and 10 healthy volunteers by phase-contrast MRI. CSF flow patterns were evaluated at seven regions of interest (ROI): the aqueduct and ventral and dorsal subarachnoid spaces of the spine at levels of the cerebellar tonsil, C2-3, and C5-6. The CSF flow waveforms were analyzed by measuring CSF circulation time, durations and maximum velocities of cranial- and caudal-directed flows, and the ratio between the two maximum velocities. Data were analyzed by ttest using SPSS 11.5.Results We found no definite communication between the fourth ventricle and syringomyelia by MRI in the 10 patients.In both the groups, we observed cranial-directed flow of CSF in the early cardiac systolic phase, which changed the direction from cranial to caudal from the middle systolic phase to the early diastolic phase, and then turned back in cranial direction in the late diastolic phase. The CSF flow disappeared at the dorsal ROI at the level of C2-3 in 3 patients and 1 volunteer, and at the level of C5-6 in 6 patients and 3 volunteers. The durations of CSF circulation at all the ROIs were significantly shorter in the patients than those in the healthy volunteers (P=0.014 at the midbrain aqueduct, P=0.019 at the inferior margin of the cerebellar tonsil, P=0.014 at the level of C2-3, and P=0.022 at the level of C5-6). No significant difference existed between the two groups in the initial point and duration of the caudal-directed CSF flow during a cardiac cycle at

  13. Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases.

    Science.gov (United States)

    Jesse, Sarah; Brettschneider, Johannes; Süssmuth, Sigurd D; Landwehrmeyer, Bernhard G; von Arnim, Christine A F; Ludolph, Albert C; Tumani, Hayrettin; Otto, Markus

    2011-06-01

    In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However, large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define a normal reference spectrum of routine CSF parameters in neurodegenerative diseases. Routine CSF parameters (white cell count, lactate and albumin concentrations, CSF/serum quotients of albumin (Q (alb)), IgG, IgA, IgM, and oligoclonal IgG bands (OCB)) were retrospectively analyzed in an academic research setting. A total of 765 patients (Alzheimer's disease (AD), Parkinson's disease (PD), Parkinson's disease dementia (PDD), vascular dementia (VD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington's disease (HD)) and non-demented control groups including a group of patients with muscular disorders (MD). The main outcome measures included statistical analyses of routine CSF parameters. Mildly elevated Q (alb) were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients with neurodegenerative diseases without elevated cell counts; lactate levels were always normal. A slightly elevated Q (alb) was observed in a subgroup of patients with neurodegenerative diseases and does not exclude the diagnosis. Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis.

  14. Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Fellmann Jere

    2006-05-01

    Full Text Available Abstract Background Abnormalities in cerebrospinal fluid (CSF production and turnover, seen in normal pressure hydrocephalus (NPH and in Alzheimer's disease (AD, may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure (CSFP, consistent with very early hydrocephalus, in a subset of AD patients enrolled in a clinical trial of chronic low-flow CSF drainage. Our objective was to determine the frequency of elevated CSFP in subjects meeting National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA criteria for AD, excluding those with signs of concomitant NPH. Methods AD subjects by NINCDS-ADRDA criteria (n = 222, were screened by history, neurological examination, and radiographic imaging to exclude those with clinical or radiographic signs of NPH. As part of this exclusion process, opening CSFP was measured supine under general anesthesia during device implantation surgery at a controlled pCO2 of 40 Torr (40 mmHg. Results Of the 222 AD subjects 181 had pressure measurements recorded. Seven subjects (3.9% enrolled in the study had CSFP of 220 mmH20 or greater, mean 249 ± 20 mmH20 which was significantly higher than 103 ± 47 mmH2O for the AD-only group. AD-NPH patients were significantly younger and significantly less demented on the Mattis Dementia Rating Scale (MDRS. Conclusion Of the AD subjects who were carefully screened to exclude those with clinical NPH, 4% had elevated CSFP. These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study.

  15. Poor Memory Performance in Aged Cynomolgus Monkeys with Hippocampal Atrophy, Depletion of Amyloid Beta 1-42 and Accumulation of Tau Proteins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Darusman, Huda S; Pandelaki, Jacub; Mulyadi, Rahmad;

    2014-01-01

    , aged cynomolgus monkeys were divided into two groups to compare high-performing (n=6) and low-performing (n=6) subjects. Both groups were tested for biomarkers related to Alzheimer's disease and their brains were scanned using structural magnetic resonance imaging. RESULTS: The subjects with poor DRT...... performance had evidence of atrophy in the hippocampus and cortical areas, significantly lower cerebrospinal fluid levels of amyloid beta amino acid 1-42 (ptau levels (p

  16. Research of essential elements composition in the cerebrospinal fluid in patients with outcomes of traumatic brain injury

    OpenAIRE

    ALIEV M.A.; MAMADALIEV A.M.; MAMADALIEVA S.A.

    2015-01-01

    The aim of this research is to investigate the essential elements composition in the cerebrospinal fluid of patients with different outcomes of traumatic brain injury before and after complex treatment with the use of endolumbal and intracystal introduction of ozone and pyracetam in dynamics. Essential elements composition was investigated in the cerebrospinal fluid of 83 patients. Thus, it may be noted positive changes in the metabolism of essential elements in the cerebrospinal fluid of pat...

  17. Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

    Directory of Open Access Journals (Sweden)

    V. B. Musatov

    2015-01-01

    Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

  18. Cerebrospinal fluid markers in Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    Gundersen Astrid S

    2008-08-01

    Full Text Available Abstract Background The objective was to assess the utility of total tau protein (tTau, the ratio of (tTau/181 phosphorylated tau protein (P-Tau and 14-3-3 protein, as diagnostic markers in cerebrospinal fluid (CSF for Creutzfeldt-Jakob disease (CJD. Methods CSF samples received from Norwegian hospitals between August 2005 and August 2007 were retrospectively selected from consecutive patients with tTau values > 1200 ng/L (n = 38. The samples from patients clinically diagnosed with CJD (n = 12 were compared to those from patients with other degenerative neurological diseases: Alzheimer's/vascular dementia (AD/VaD, n = 21, other neurological diseases (OND, n = 5. Total Tau, P-Tau, and β-Amyloid (Aβ42 were measured with commercial kits. Additionally, 14-3-3 protein was measured semi-quantitatively by immunoblot. Results The minimum cut-off limits for diagnosis of CJD were chosen from the test results. For tTau the lower limit was fixed at 3000 ng/L, for the tTau/P-Tau ratio it was 60, and for 14-3-3 protein it was 0.75 arbitrary units. For tTau and tTau/P-Tau ratio, all but three CJD patients had levels above the minimum, whereas almost all of the other patients were below. For the 14-3-3 protein, two CJD patients were below the minimum and five were above. Only one of the other patients was higher than the limit. The sensitivities, specificities and diagnostic efficiencies were: tTau 75%, 92%, and 87%; tTau/P-Tau 75%, 96%, and 89%; and 14-3-3 protein 80%, 96%, and 91%. Conclusion The results suggest that 14-3-3 protein may be the better marker for CJD, tTau/P-Tau ratio and tTau are also efficient markers, but showed slightly inferior diagnostic properties in this study, with tTau/P-Tau marginally better than tTau.

  19. Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome.

    Science.gov (United States)

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

    During early stages of embryo development, the brain cavity is filled with Embryonic Cerebro-Spinal Fluid, which has an essential role in the survival, proliferation and neurogenesis of the neuroectodermal stem cells. We identified and analyzed the proteome of Embryonic Cerebro-Spinal Fluid from rat embryos (Rattus norvegicus), which includes proteins involved in the regulation of Central Nervous System development. The comparison between mammalian and avian Embryonic Cerebro-Spinal Fluid proteomes reveals great similarity, but also greater complexity in some protein groups. The pattern of apolipoproteins and enzymes in CSF is more complex in the mammals than in birds. This difference may underlie the greater neural complexity and synaptic plasticity found in mammals. Fourteen Embryonic Cerebro-Spinal Fluid gene products were previously identified in adult human Cerebro-Spinal Fluid proteome, and interestingly they are altered in patients with neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis may contribute to our understanding of Central Nervous System development and evolution, and these human diseases. PMID:16335996

  20. Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults.

    Science.gov (United States)

    Mattsson, Niklas; Insel, Philip; Nosheny, Rachel; Trojanowski, John Q; Shaw, Leslie M; Jack, Clifford R; Tosun, Duygu; Weiner, Michael

    2014-03-01

    Biomarkers associated with Alzheimer's disease (AD)-like brain atrophy in healthy individuals may identify mechanisms involved in early stage AD. Aside from cerebrospinal fluid (CSF) β-amyloid42 (Aβ42) and tau, no studies have tested associations between CSF proteins and AD-like brain atrophy. We studied 90 healthy elders, who underwent lumbar puncture at baseline, and serial magnetic resonance imaging scans for up to 4 years. We tested statistical effects of baseline CSF proteins (N = 70 proteins related to Aβ42-metabolism, microglial activity, and synaptic/neuronal function) on atrophy rates in 7 AD-related regions. Besides the effects of Aβ42 and phosphorylated tau (P-tau) that were seen in several regions, novel CSF proteins were found to have effects in inferior and middle temporal cortex (including apolipoprotein CIII, apolipoprotein D, and apolipoprotein H). Several proteins (including S100β and matrix metalloproteinase-3) had effects that depended on the presence of brain Aβ pathology, as measured by CSF Aβ42. Other proteins (including P-tau and apolipoprotein D) had effects even after adjusting for CSF Aβ42. The statistical effects in this exploratory study were mild and not significant after correction for multiple comparisons, but some of the identified proteins may be associated with brain atrophy in healthy persons. Proteins interacting with CSF Aβ42 may be related to Aβ brain pathology, whereas proteins associated with atrophy even after adjusting for CSF Aβ42 may be related to Aβ-independent mechanisms.

  1. Cerebrospinal fluid analysis detects cerebral amyloid-β accumulation earlier than positron emission tomography

    OpenAIRE

    Palmqvist, Sebastian; Mattsson, Niklas; Hansson, Oskar; ,

    2016-01-01

    See Rabinovici (doi:10.1093/brain/aww025) for a scientific commentary on this article. Cerebral accumulation of amyloid-β is thought to be the starting mechanism in Alzheimer’s disease. Amyloid-β can be detected by analysis of cerebrospinal fluid amyloid-β42 or amyloid positron emission tomography, but it is unknown if any of the methods can identify an abnormal amyloid accumulation prior to the other. Our aim was to determine whether cerebrospinal fluid amyloid-β42 change before amyloid PET ...

  2. Ultrastructural changes of bone marrow cells exposed for xenogenous cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Shaymardanova L.R.

    2010-01-01

    Full Text Available Due to the scientifical investigations xenogenous cerebrospinal fluid was considered as possible substance for theproduction of powerful adaptogen of biological origin. One of the representative research in these field demonstrates morphologicaland functional changes of bone marrow as the central hemopoetic and immune organ. The article shows the ultramicroscopicchanges of bone marrow cells after the xenogenous cerebrospinal fluid exposure in Vistar rats of differentage. It was revealed the activation of synthetic processes in bone marrow cells of the first three age groups and exhaustion ofactivating mechanisms in the fourth age group, that was manifested in swelling and destruction of mytochondria, vacuolisationof cytoplasm, invagination of caryolemma.

  3. 1H-NMR studies of cerebrospinal fluid: endogenous ethanol in patients with cervical myelopathy.

    Science.gov (United States)

    Meshitsuka, S; Morio, Y; Nagashima, H; Teshima, R

    2001-10-01

    Endogenous ethanol was observed by nuclear magnetic resonance spectroscopy in the course of screening for cerebrospinal fluid of the patients with cervical myelopathy. Ethanol was detected in 10 out of 20 patients. It seems likely that the presence of endogenous ethanol is related to the severity of myelopathy. Also, the concentration of ethanol was correlated with that of lactate in the cerebrospinal fluid. This implies that ethanol may be formed as the end product of glycolysis or in an unknown pathway in the case of severely insulted myelonic tissues.

  4. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking

    DEFF Research Database (Denmark)

    Teunissen, C E; Petzold, A; Bennett, J L;

    2009-01-01

    There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because o...

  5. A Selected Reaction Monitoring (SRM)-Based Method for Absolute Quantification of Aβ38, Aβ40, and Aβ42 in Cerebrospinal Fluid of Alzheimer's Disease Patients and Healthy Controls

    DEFF Research Database (Denmark)

    Pannee, Josef; Portelius, Erik; Oppermann, Madalina;

    2013-01-01

    Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in research centers, clinical trials, and clinical settings. However, their broad-scale use is hampered by lack of standardization across analytical platforms and by interference from binding of amyloid-β (Aβ)...

  6. Cytomegalovirus associated transverse myelitis in an immunocompetent host with DNA detection in cerebrospinal fluid; a case report

    OpenAIRE

    Karunarathne Suneth; Govindapala Dumitha; Udayakumara Yapa; Fernando Harshini

    2012-01-01

    Abstract Background Cytomegalovirus associated transverse myelitis among immunocompetent adults has been rarely reported. We report a patient presenting with clinical myelitis followed by previously unreported finding of cytomegalovirus deoxyribonucleic acid in cerebrospinal fluid. Case report A forty year old immunocompetent male presented with acute onset progressive bilateral lower limb weakness. His spinal magnetic resonance imaging findings, cerebrospinal fluid analysis and clinical pict...

  7. [A Case of Spontaneous Cerebrospinal Fluid Leak Associated with Cervical Spondylosis].

    Science.gov (United States)

    Arai, Atsushi; Miyamoto, Hirohito; Shiomi, Ryoji; Tatsumi, Shotaro; Kohmura, Eiji

    2016-09-01

    Spontaneous cerebrospinal fluid leak and intracranial hypotension associated with cervical spondylosis have rarely been observed, and only a few cases are reported. A 69-year-old woman, previously treated for rectal and thyroid cancer, complained of a non-postural persistent headache. The patient regularly practiced aerobic exercise, but a month earlier she had started experiencing headache and neck pain while exercising. Computed tomography(CT)showed bilateral chronic subdural hematomas, and magnetic resonance imaging(MRI)revealed diffuse dural enhancement and tonsillar herniation. We drained the subdural hematomas and replaced the ventricular reservoir to safely access the cerebrospinal fluid space. After surgery, the persistent headache disappeared for several days, but a postural headache emerged. CT myelogram showed extradural accumulation of the contrast medium at the C2-5 level with cervical spondylosis. The patient was treated with conservative therapy of bed rest and intravenous fluid hydration for two weeks, and the headache improved. CT myelogram after treatment showed no extradural accumulation of the contrast medium. Spontaneous cerebrospinal fluid leak associated with cervical spondylosis could be induced by the repeated minor mechanical stress caused by physical exercise. Therefore, the possibility that non-postural persistent headache may be caused by spontaneous cerebrospinal fluid leak should not be underestimated. PMID:27605479

  8. Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Henriksen, Louise T; Nersting, Jacob; Raja, Raheel A;

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The...

  9. Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary progressive multiple sclerosis

    NARCIS (Netherlands)

    M.P. Stoop (Marcel); V. Singh (Vaibhav); L.J.M. Dekker (Lennard); M.K. Titulaer (Mark); C. Stingl (Christoph); P.C. Burgers (Peter); P.A.E. Sillevis Smitt (Peter); R.Q. Hintzen (Rogier); T.M. Luider (Theo)

    2010-01-01

    textabstractBackground: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a n

  10. Increased total-Tau levels in cerebrospinal fluid of pediatric hydrocephalus and brain tumor patients

    NARCIS (Netherlands)

    de Bont, Judith M.; Vanderstichele, Hugo; Reddingius, Roel E.; Pieters, Rob; van Gool, Stefdan W.

    2008-01-01

    Total Tau (t-Tau), hyperphosphorylated Tau (p-Tau((181P))) and beta-amyloid((1-42)) in cerebrospinal fluid (CSF) have shown to be markers of neuronal and axonal degeneration in various neurological and neurodegenerative diseases. The aim of this study was to evaluate the influence of the presence of

  11. Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome.

    Directory of Open Access Journals (Sweden)

    Sofia Temudo Duarte

    Full Text Available OBJECTIVE: Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. METHODS: The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life and from Rett syndrome patients (2 to 19 years of life, by immunoblot analysis. RESULTS: Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. CONCLUSIONS: Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.

  12. A rapid and simple cannulation technique for repeated sampling of cerebrospinal fluid in freely moving rats

    NARCIS (Netherlands)

    Bouman, H.J.; Wimersma Greidanus, T.B. van

    1979-01-01

    A cannulation technique for frequent sampling of cerebrospinal fluid (CSF) in unanaesthetized freely moving rats is described. A permanent stainless steel cannula, constructed in such a way that no loss of CSF occurs, is placed into the rat's cisterna magna and fixed to the skull by anchoring screws

  13. Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice.

    NARCIS (Netherlands)

    Leen, W.G.; Willemsen, M.A.A.P.; Wevers, R.A.; Verbeek, M.M.

    2012-01-01

    Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of many neurological disorders, but reference ranges for CSF glucose, CSF/plasma glucose ratio and CSF lactate based on studies with large numbers of CSF samples are not available. Our aim was to define age-specific re

  14. Cerebrospinal fluid amyloid beta42/phosphorylated tau ratio discriminates between Alzheimer's disease and vascular dementia.

    NARCIS (Netherlands)

    Jong, D. de; Jansen, R.W.M.M.; Kremer, H.P.H.; Verbeek, M.M.

    2006-01-01

    BACKGROUND: The differentiation of Alzheimer's disease (AD) from vascular dementia (VaD) is hampered by clinical diagnostic criteria with disappointing sensitivity and specificity. The objective of this study was to investigate whether cerebrospinal fluid (CSF) levels of total tau protein (t-tau), a

  15. Bace1 activity in cerebrospinal fluid and its relation to markers of ad pathology

    NARCIS (Netherlands)

    Mulder, S.D.; Flier, W.M. van der; Verheijen, J.H.; Mulder, C.; Scheltens, P.; Blankenstein, M.A.; Hack, C.E.; Veerhuis, R.

    2010-01-01

    Several studies have shown that reduced amyloid-β 1-42 (Aβ {42}) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. β-site APP cleaving enzyme (BACE1) is thought to be the major β-secretase involved in Aβ production in the brain,

  16. Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis

    NARCIS (Netherlands)

    Koch, M.; Heersema, D.; Mostert, J.; Teelken, A.; De Keyser, J.

    2007-01-01

    Antibody-mediated inflammation is believed to contribute to tissue injury in multiple sclerosis (MS). The majority of patients with MS have oligoclonal bands (OCB), corresponding to antibodies against a variety of antigens, in their cerebrospinal fluid (CSF). The relation of CSF OCB and disease prog

  17. Determination of ammonia in cerebrospinal fluid using the indophenol direct method

    NARCIS (Netherlands)

    Huizenga, [No Value; Teelken, AW; Tangerman, A; de Jager, AEJ; Gips, CH; Jansen, PLM

    1998-01-01

    We have determined ammonia in cerebrospinal fluid (CSF) with the indophenol direct method. The results were compared with an enzymatic method. The method is very simple, and precision (coefficient of variation 1.6%) and linearity (r = 0.9999, p <0.001) of the method are excellent. The recoveries of

  18. Cerebrospinal fluid flow and production in patients with normal pressure hydrocephalus studied by MRI

    DEFF Research Database (Denmark)

    Gideon, P; Ståhlberg, F; Thomsen, C;

    1994-01-01

    An interleaved velocity-sensitised fast low-angle shot pulse sequence was used to study cerebrospinal fluid (CSF) flow in the cerebral aqueduct, and supratentorial CSF production in 9 patients with normal pressure hydrocephalus (NPH) and 9 healthy volunteers. The peak aqueduct CSF flow, both caudal...

  19. Primary low cerebrospinal fluid pressure syndrome with galactorrhea: findings at MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, A.; Morita, N.; Yoshida, S.; Yamamoto, M.; Hashimoto, K. [Kochi Medical School (Japan)

    1996-04-01

    A case of primary low cerebrospinal fluid (CSF) pressure syndrome with galactorrhea is reported. Magnetic resonance imaging demonstrated diffusely enhanced meninges, edematous brian, and enlarged pituitary gland. Coincidental enlargement of pituitary gland and edematous brain due to low CSF pressure compressed the pituitary portal system. The low-perfused anterior lobe of pituitary gland would be the mechanism of galactorrhea. 13 refs., 2 figs.

  20. Levels of arginine-vasopressin in cerebrospinal fluid during passive avoidance behavior in rats

    NARCIS (Netherlands)

    Kloet, E.R. de; Laczi, F.; Gaffori, O.; Fekete, M.; Wied, D. de

    1984-01-01

    The concentration of immunoreactive arginine-vasopressin (IR-AVP) was measured in the cerebrospinal fluid (CSF) during acquisition and retention of passive avoidance behavior. IR-AVP level in CSF of male Wistar rats immediately after the learning trial was increased; the rate of which was related to

  1. Therapy failure following selection of enfuvirtide-resistant HIV-1 in cerebrospinal fluid

    NARCIS (Netherlands)

    van Lelyveld, S F L; Nijhuis, M; Baatz, F; Wilting, I; van den Bergh, W M; Kurowski, M; de Jong, D.; Hoepelman, A I M; Wensing, A M J

    2010-01-01

    We report the selection of enfuvirtide-resistant human immunodeficiency virus type 1 in cerebrospinal fluid, resulting in subsequent loss of viral suppression in the plasma. This case report emphasizes the potential danger of low-level penetration of entry inhibitors into the central nervous system.

  2. Pharmacokinetics of Moxifloxacin in Cerebrospinal Fluid and Plasma in Patients with Tuberculous Meningitis

    NARCIS (Netherlands)

    Alffenaar, J. W. C.; van Altena, R.; Bokkerink, H. J.; Luijckx, G. J.; van Soolingen, D.; Aarnoutse, R. E.; van der Werf, T. S.

    2009-01-01

    Moxifloxacin cerebrospinal fluid (CSF) penetration was evaluated by obtaining full plasma and CSF time concentration curves for 4 patients with tuberculous meningitis. The geometric mean ratio of the areas under the curve for CSF to plasma were 0.82 (range, 0.70-0.94) at 400 mg once per day and 0.71

  3. Pharmacokinetics of moxifloxacin in cerebrospinal fluid and plasma in patients with tuberculous meningitis.

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Altena, R. van; Bokkerink, H.J.; Luijckx, G.J.R.; Soolingen, D. van; Aarnoutse, R.E.; Werf, T.S. van der

    2009-01-01

    Moxifloxacin cerebrospinal fluid (CSF) penetration was evaluated by obtaining full plasma and CSF time concentration curves for 4 patients with tuberculous meningitis. The geometric mean ratio of the areas under the curve for CSF to plasma were 0.82 (range, 0.70-0.94) at 400 mg once per day and 0.71

  4. Glycemia and Levels of Cerebrospinal Fluid Amyloid and Tau in Patients Attending a Memory Clinic

    NARCIS (Netherlands)

    Exalto, Lieza G.; van der Flier, Wiesje M.; Scheltens, Phillip; Biessels, Geert Jan

    2010-01-01

    OBJECTIVES: To determine the association between markers of glycemia and cerebrospinal fluid (CSF) amyloid beta 1-42 (A beta 42) and tau levels in patients attending a memory clinic. DESIGN: Cross-sectional study. SETTING: Memory clinic. PARTICIPANTS: Two hundred forty-five consecutive patients atte

  5. (alpha)B-crystallin in cerebrospinal fluid of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Støvring, Birgitte; Vang, Ole; Christiansen, Michael

    2005-01-01

    Background: aB-crystallin is a chaperone protein and a potential myelin antigen to human T cells in Multiple Sclerosis (MS). In this study we investigate the existence of aB-crystallin in the cerebrospinal fluid (CSF) of patients with clinical symptoms of MS and control individuals without these ...

  6. Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration.

    Science.gov (United States)

    Popa, D; Loewenstein, L; Lam, S W; Neuner, E A; Ahrens, C L; Bhimraj, A

    2016-02-01

    Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose.

  7. Dissociable brain biomarkers of fluid intelligence.

    Science.gov (United States)

    Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

    2016-08-15

    Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. PMID:27184204

  8. Prediction of bacterial meningitis based on cerebrospinal fluid pleocytosis in children

    Directory of Open Access Journals (Sweden)

    Sofia Águeda

    2013-08-01

    Full Text Available Children with cerebrospinal fluid pleocytosis are frequently treated with parenteral antibiotics, but only a few have bacterial meningitis. Although some clinical prediction rules, such as bacterial meningitis score, are of well-known value, the cerebrospinal fluid white blood cells count can be the initial available information. Our aim was to establish a cutoff point of cerebrospinal fluid white blood cell count that could distinguish bacterial from viral and aseptic meningitis. A retrospective study of children aged 29 days to 17 years who were admitted between January 1st and December 31th, 2009, with cerebrospinal fluid pleocytosis (white blood cell > 7 µL-1 was conducted. The cases of traumatic lumbar puncture and of antibiotic treatment before lumbar puncture were excluded. There were 295 patients with cerebrospinal fluid pleocytosis, 60.3% females, medium age 5.0 ± 4.3 years distributed as: 12.2% 1-3 months; 10.5% 3-12 months; 29.8% 12 months to 5 years; 47.5% >5 years. Thirty one children (10.5% were diagnosed with bacterial meningitis, 156 (52.9% viral meningitis and 108 (36.6% aseptic meningitis. Bacterial meningitis was caused by Neisseria meningi tidis (48.4%, Streptococcus pneumoniae (32.3%, other Streptococcus species (9.7%, and other agents (9.7%. cerebrospinal fluid white blood cell count was significantly higher in patients with bacterial meningitis (mean, 4839 cells/µL compared to patients with aseptic meningitis (mean, 159 cells/µL, p < 0.001, with those with aseptic meningitis (mean, 577 cells/µL, p < 0.001 and with all non-bacterial meningitis cases together (p < 0.001. A cutoff value of 321 white blood cell/µL showed the best combination of sensitivity (80.6% and specificity (81.4% for the diagnosis of bacterial meningitis (area under receiver operating characteristic curve 0.837. Therefore, the value of cerebrospinal fluid white blood cell count was found to be a useful and rapid diagnostic test to distinguish

  9. Leukocyte-derived microparticles and scanning electron microscopic structures in two fractions of fresh cerebrospinal fluid in amyotrophic lateral sclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Zachau Anne C

    2012-09-01

    lipid appearance, sticking together in a viscous batter. The quantitative increase in scanning electron microscopy findings corresponded to the flow cytometry result of an increase in leukocyte-derived microparticles. Conclusions Microparticles represent subcellular arrangements that can influence the pathogenesis of amyotrophic lateral sclerosis and may serve as biomarkers for underlying cellular disturbances. The increased number of leukocyte-derived microparticles with normal cell counts in cerebrospinal fluid may contribute to the amyotrophic lateral sclerosis inflammatory process by formation of immune complexes of prion-like propagation, possibly due to misfolded proteins. The two complementary methods used in this report may be additional tools for revealing the etiology of amyotrophic lateral sclerosis, for early diagnostic purposes and for evaluation of clinical trials, long-term follow-up studies and elucidating the pathophysiology in amyotrophic lateral sclerosis.

  10. Cerebrospinal fluid from patients with subarachnoid haemorrhage and vasospasm enhances endothelin contraction in rat cerebral arteries.

    Directory of Open Access Journals (Sweden)

    Barbara Assenzio

    Full Text Available INTRODUCTION: Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. METHODS: Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1 SAH patients with vasospasm, 2 SAH patients without vasospasm, and 3 control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. RESULTS: Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1 larger contractions at lower endothelin concentrations (p<0.05; 2 the increased endothelin contraction was absent in arteries without endothelium; 3 higher levels of endothelin secretion in the culture medium (p<0.05; 4 there was expression of ETA receptors and new expression of ETB receptors was apparent; 5 reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6 after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. CONCLUSIONS: Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in

  11. Immuno-reactive somatostatin in the cerebro-spinal fluid. Immunreaktives Somatostatin im Liquor cerebrospinalis

    Energy Technology Data Exchange (ETDEWEB)

    Kohler, J.

    1983-01-01

    In the present work the lumbar cerebro-spinal fluid of 178 patients with different neurological affections was examined with the aid of a specific radioimmunoassay for somatostatin. 18 patients without any pathologic neurological findings served as controls. In degenerative diseases of the brain, reduced somatostatin levels in the cerebro-spinal fluid as compared to the controls were measured. In 3 patients with isolated cerebellar atrophy no reduction of the somatostatin content was found; rather the values were highly normal. Huntington-Chorea also is a case apart. In patients with manifest affections, the somatostatin reduction, amounting to 54.6%, was particularly notable as compared to the controls. By contrast, degenerative diseases with predominant medullary and spastic affection are characterized by significantly increased somatostatin levels. Again, in non-spastic patients the values were not significantly different from those of the controls. Patients with inflammations of the brain and meminges as well as with tumors of the nervous system showed somatostatin levels increased by about 60.8% respectively 51.8% as compared to the controls. Epileptic patients normally exhibit a reduced somatostatin level in the cerebro-spinal fluid, but the reduction is not significant. Disseminated encephalomyclitis, whether chromic or acute, is not found to be associated with significant modifications of the somatostatin level in the cerebro-spinal fluid. Strikingly, however, patients in which the disease took a serious or very serious clinical course showed also the lowest somatostatin levels in the cerebro-spinal fluid. In patients exhibiting the roof compression symptom in consequence of a prolapse of the disk, no significant modifications were found. By contrast, in patients with the symptoms of a transverse lesion, significantly increased somatostatin values were measured.

  12. Cortisol in plasma and cerebrospinal fluid of patients with brain ischemia

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2004-01-01

    Full Text Available Introduction One of the reactions to ischemia is increased release of glucocorticoid hormones, included in regulation of effects of numerous mediators/modulators that could be released in the acute phase of brain ischemia. The aim of our investigation was to define temporal dynamics of cortisol concentrations in plasma and cerebrospinal fluid of patients with different types of ischemic brain disease. Material and methods The study included 263 patients of both sexes, aged 55-68 years. History, clinical examination and cerebral computerized tomography were performed to establish the diagnosis. 97 patients had brain infarction, 66 had a reversible ischemic attack, 66 had a transient ischemic attack, and 34 patients had chronic encephalopathy. The control group included 22 age- and sex- matched patients, subjected to diagnostic lumbar radiculography, without disturbances in the cerebrospinal fluid passage. Cortisol concentrations were measured by direct radioimmunoassay. Results and discussion Results obtained in this research showed that in acute brain ischemic period there was a significant increase of cortisol concentration in plasma and cerebrospinal fluid. The increase was highest in patients with brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack compared to controls (331.7±92.8 pmol/ml of plasma and 2.5±1.1 pmol/ml of cerebrospinal fluid. Maximum concentrations were found during the first two days after insult. The main potentially protective effects of increased cortisol concentrations in patients with acute stroke could be the decrease of effects of deleterious reactions induced by ischemia. This mechanism might be an attempt of organism to compensate for disturbed homeostasis. Conclusion Measurement of cortisol in plasma and cerebrospinal fluid in patients with acute stroke is significant for monitoring the intensity of response of an organism to acute brain damage.

  13. Detection of an occult transclival cerebrospinal fluid fistula by CT and MRI

    International Nuclear Information System (INIS)

    We describe an unusual occult transclival cerebrospinal fluid (CSF) fistula to the sphenoid sinus demonstrated by MRI. CT was performed because of a posterior cerebral infarct caused by cardiac arrhythmia. Axial sections showed fluid in the sphenoid sinus. High-resolution scans revealed a bony defect 3 mm in diameter of the posterior wall of the sphenoid sinus, and MRI showed a transclival CSF fistula. This occult lesion was confirmed by surgery and duraplasty was successfully performed via an endonasal approach. (orig.)

  14. The Diagnostic and Differential Diagnosis Utility of Cerebrospinal Fluid α -Synuclein Levels in Parkinson's Disease: A Meta-Analysis.

    Science.gov (United States)

    Zhou, Bo; Wen, Min; Yu, Wen-Feng; Zhang, Chun-Lin; Jiao, Ling

    2015-01-01

    Several recent studies showed that α-syn might be a potential diagnostic biomarker for PD in human cerebrospinal fluid (CSF), but the results were inconsistent. The purpose of this meta-analysis was to investigate the diagnostic and differential diagnosis efficacy of CSF α-syn in PD. Studies which measured CSF α-syn or α-syn oligomers in patients with PD and met the inclusion criteria were included in the analysis. Results of the meta-analysis indicated that mean concentration of CSF α-syn was significantly lower in PD compared to controls and significantly higher in PD compared to multiple system atrophy (MSA). No significant difference in mean concentration of CSF α-syn was found between PD and dementia with Lewy bodies (DLB). Mean concentration of CSF α-syn was slightly decreased in PD compared to progressive supranuclear palsy (PSP). Mean concentration of CSF α-syn oligomers was significantly higher in PD than control. These results support the findings that CSF α-syn may be a potential diagnostic and differential diagnosis biomarker in PD compared to control and MSA but not DLB. Furthermore, α-syn oligomer may represent a better biomarker for diagnosis of PD.

  15. Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children.

    Science.gov (United States)

    Carson, D S; Berquist, S W; Trujillo, T H; Garner, J P; Hannah, S L; Hyde, S A; Sumiyoshi, R D; Jackson, L P; Moss, J K; Strehlow, M C; Cheshier, S H; Partap, S; Hardan, A Y; Parker, K J

    2015-09-01

    The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.

  16. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer's Disease in Human Cerebrospinal Fluid.

    Directory of Open Access Journals (Sweden)

    Ronald C Hendrickson

    Full Text Available Disease modifying treatments for Alzheimer's disease (AD constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001 and SME-2 (p = 0.0004 for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR, in AD were 21% (p = 0.039 and 17% (p = 0.026 lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic.

  17. Embryonic cerebrospinal fluid regulates neuroepithelial survival, proliferation, and neurogenesis in chick embryos.

    Science.gov (United States)

    Gato, Angel; Moro, J A; Alonso, M I; Bueno, D; De La Mano, A; Martín, C

    2005-05-01

    Early in development, the behavior of neuroepithelial cells is controlled by several factors, which act in a developmentally regulated manner. Diffusible factors are secreted locally by the neuroepithelium itself, although other nearby structures may also be involved. Evidence suggests a physiological role for the cerebrospinal fluid in the development of the brain. Here, using organotypic cultures of chick embryo neuroepithelial explants from the mesencephalon, we show that the neuroepithelium in vitro is not able to self-induce cell survival, replication, and neurogenesis. We also show that the embryonic cerebrospinal fluid (E-CSF) promotes neuroepithelial stem cell survival and induces proliferation and neurogenesis in mesencephalic explants. These data strongly suggest that E-CSF is involved in the regulation of neuroepithelial cells behavior, supporting the hypothesis that this fluid plays a key role during the early development of the central nervous system. PMID:15803475

  18. Development of a theoretical framework for analyzing cerebrospinal fluid dynamics

    DEFF Research Database (Denmark)

    Cohen, Benjamin; Voorhees, Abram; Vedel, Søren;

    2009-01-01

    Background: To date hydrocephalus researchers acknowledge the need for rigorous but utilitarian fluid mechanics understanding and methodologies in studying normal and hydrocephalic intracranial dynamics. Pressure volume models and electric circuit analogs introduced pressure into volume conservat......Background: To date hydrocephalus researchers acknowledge the need for rigorous but utilitarian fluid mechanics understanding and methodologies in studying normal and hydrocephalic intracranial dynamics. Pressure volume models and electric circuit analogs introduced pressure into volume...

  19. Regional cerebral metabolic rate for glucose and cerebrospinal fluid monoamine metabolites in subacute sclerosing panencephalitis

    International Nuclear Information System (INIS)

    Regional cerebral metabolic rate for glucose (rCMRglu) and cerebrospinal fluid monoamine metabolites were measured in two cases of subacute sclerosing panencephalitis (SSPE) with different clinical courses. A marked decrease in rCMRglu was found in the cortical gray matter of a patient with rapidly developing SSPE (3.6 - 4.2 mg/100 g brain tissue/min). However, the rCMRglu was preserved in the caudate and lenticular nuclei of the patient (7.7 mg/100 g/min). The rCMRglu in a patient with slowly developing SSPE revealed patterns and values similar to those of the control. Cerebrospinal fluid monoamine metabolites ; homovanilic acid and 5-hydroxyindoleacetic acid, were decreased in both rapidly and slowly developing SSPE. These data indicated that rCMRglu correlated better with the neurological and psychological status and that dopaminergic and serotonergic abnormalities have been implicated in pathophysiology of SSPE. (author)

  20. Spinal cerebrospinal fluid seeding of a clival chordoma; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Hwan; Yu, In Kyu; Kim, Seong Min; Park, Ki Seok; Son, Hyun Jin [Eulji University Hospital, Daejeon (Korea, Republic of)

    2015-07-15

    Chordomas originate from remnants of the embryonic notochord and account for < 2% of all malignant bone tumors. Chordomas have a high rate of local recurrence. However, spinal cerebrospinal fluid (CSF) seeding of a chordoma is extremely rare. Here, we present a very rare case of clival chordoma with spinal seeding. Radiologists should consider spinal CSF seeding of a clival chordoma, particularly when accompanied by signs of dural perforation or caudal extension.

  1. Occurrence of Overlooked Zoonotic Tuberculosis: Detection of Mycobacterium bovis in Human Cerebrospinal Fluid

    OpenAIRE

    Shah, N.P.; Singhal, A.; A Jain; P. Kumar; Uppal, S. S.; Srivatsava, M. V. P.; Prasad, H. K.

    2006-01-01

    The paucibacillary nature of the cerebrospinal fluid (CSF) has been a major obstacle in the diagnosis of human tuberculous meningitis (TBM). This study shows that with molecular techniques direct precise determination to the species level of mycobacterial pathogens can be made. The present report describes the utility of a nested PCR (N-PCR) assay (A. Mishra, A. Singhal, D. S. Chauhan, V. M. Katoch, K. Srivastava, S. S. Thakral, S. S. Bharadwaj, V. Sreenivas, and H. K. Prasad, J. Clin. Microb...

  2. Acute Subdural Hematoma Following Spinal Cerebrospinal Fluid Drainage in a Patient with Freezing of Gait

    OpenAIRE

    Kim, Han-Joon; Cho, Yong-Jin; Cho, Joong-Yang; Lee, Dong-Ha; Hong, Keun-Sik

    2009-01-01

    Background Headache is a common complication of lumbar puncture (LP). Although in most cases post-LP headaches are not severe and have a benign course, they can also be a manifestation of a potentially life-threatening complication such as subdural hematoma (SDH). Case Report We describe a patient in whom a massive SDH developed after LP and cerebrospinal fluid (CSF) drainage, which were performed during the diagnostic evaluation of freezing of gait. Conclusions SDH should not be excluded fro...

  3. P08.04LEPTOMENINGEAL CARCINOMATOSIS VS LEPTOMENINGEAL LYMPHOMATOSIS: COMPARISON OF THE CEREBROSPINAL FLUID INFLAMMATORY CELLS

    OpenAIRE

    Subirá, D.; Simó, M.; Illán, J.; Castañón, S.; Gonzalo, R; Martínez-García, M.; Pardo, J.; Gómez, L.; Navarro, M.; Bruna, J

    2014-01-01

    BACKGROUND: The inflammatory-cell infiltrate surrounding solid tumours is progressively gaining importance, in an attempt to reach a better understanding of the pathophysiology of the disease, and also improve future design of immune-based cancer therapies. However, information about the inflammatory cell populations in leptomeningeal disease is scarce. STUDY DESIGN: We have studied the distribution of the main inflammatory cell populations in the cerebrospinal fluid (CSF) from 83 patients di...

  4. Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with Amyotrophic Lateral Sclerosis

    OpenAIRE

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, we...

  5. Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome

    OpenAIRE

    P. Lestaevel; Grison, S.; Favé, G.; Elie, C.; B. Dhieux; Martin, J.C.; Tack, K.; Souidi, M.

    2016-01-01

    Natural uranium (NU), a component of the earth’s crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drin...

  6. The influence of xenogenic cerebrospinal fluid over the parenchyma of rat's lungs after single total irradiation

    OpenAIRE

    Shatov D.V.; Pikalyuk V.S.; Shalanin V.V.; Shimkus T.S.

    2014-01-01

    Background. One of the results of negative influence of irradiation is the radiational injury of lungs, which manifests itself by radiational pneumonitis and pulmonary fibrosis. The medicines of phytogenous and animal origin, microelements and synthetic analogs of natural organism protection's substances, high-molecular compounds, vaccines, cytokines and their inductors are used for early therapy of these complications. As one of such remedies one can use the xenogenic cerebrospinal fluid of ...

  7. Comparative Evaluation of Colorimetric Microtiter Plate Systems for Detection of Herpes Simplex Virus in Cerebrospinal Fluid

    OpenAIRE

    Tang, Yi-Wei; Rys, Paul N.; Rutledge, Barbara J.; Mitchell, P. Shawn; Smith, Thomas F.; Persing, David H.

    1998-01-01

    In the past few years, application of the PCR to the detection of herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) from patients with encephalitis and meningitis has become standard laboratory practice. However, from an operational perspective, the true diagnostic value of PCR in this setting is yet to be realized because most laboratories subject the amplification products to lengthy probe hybridization procedures by Southern blotting. As alternatives to Southern blotting, we ...

  8. Levels of arginine-vasopressin in cerebrospinal fluid during passive avoidance behavior in rats

    OpenAIRE

    Kloet, E.R. de; Laczi, F.; Gaffori, O.; Fekete, M.; Wied, D. de

    1984-01-01

    The concentration of immunoreactive arginine-vasopressin (IR-AVP) was measured in the cerebrospinal fluid (CSF) during acquisition and retention of passive avoidance behavior. IR-AVP level in CSF of male Wistar rats immediately after the learning trial was increased; the rate of which was related to the intensity of the electric footschock during the learning trial and the avoidance latency as measured 1 day after the learning trial. Immediately after the 24 h retention test IR-AVP levels wer...

  9. S-Adenosylmethionine is decreased in the cerebrospinal fluid of patients with Alzheimer's disease

    OpenAIRE

    Linnebank, M.; Popp, J.; Smulders, Y.; Smith, D.; Semmler, A; Farkas, M.; Kulic, L.; Cvetanovska, G; Blom, H; Stoffel-Wagner, B.; Kölsch, H; Weller, M.; Jessen, F.

    2010-01-01

    Background: Increased plasma homocysteine levels have been described as an independent risk factor for Alzheimer's disease (AD), but the underlying pathophysiology is unclear. Objective: This single-center, cross-sectional, correlational study analyzed homocysteine metabolism in 60 AD patients and 60 control subjects. Methods: Fasting plasma levels of vitamin B(12), folate and homocysteine as well as cerebrospinal fluid (CSF) levels of folate derivates, S-adenosylmethionine (SAM), S-adenosylh...

  10. Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis

    OpenAIRE

    Stoop, Marcel P.; Vaibhav Singh; Dekker, Lennard J; Titulaer, Mark K; Christoph Stingl; Burgers, Peter C.; Sillevis Smitt, Peter A.E.; Hintzen, Rogier Q; Luider, Theo M.

    2010-01-01

    textabstractBackground: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. Methodology/Principal Findings: ...

  11. Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis

    OpenAIRE

    Almeida, Sergio Monteiro de; Bhatt, Archana; Riggs, Patricia K.; Durelle, Janis; Lazzaretto, Deborah; Marquie-Beck, Jennifer; McCutchan, Allen; Letendre, Scott; Ellis, Ronald

    2010-01-01

    Syphilis is a frequent coinfection with human immunodeficiency virus (HIV). Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load; VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We hypothesized that intrathecal immune activation in neurosyphilis would selectively increase CSF VL in coinfected patients. In this study, HIV-infected research subjects (N = 225) were categorized into three groups based on serum rapid plasma reagin (RPR), microhemagl...

  12. Fluoride in cerebrospinal fluid of patients with fluorosis.

    OpenAIRE

    Hu, Y H; Wu, S S

    1988-01-01

    The CSF fluoride level of individuals drinking water with normal fluoride content and of patients with endemic fluorosis were studied. For the purpose of studying the relationship between the dynamic equilibrium of the CSF fluoride and other body fluids, urine and blood fluoride were examined simultaneously. Fluoride was revealed in every CSF sample of the control group and its mean value was lower than that of the blood. The CSF fluoride concentration of patients with fluorosis was slightly ...

  13. Utility of Measuring (1,3)-β-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection

    OpenAIRE

    Lyons, Jennifer L.; Thakur, Kiran T.; Lee, Rick; Watkins, Tonya; Pardo, Carlos A.; Carson, Kathryn A.; Markley, Barbara; Finkelman, Malcolm A.; Kieren A Marr; Roos, Karen L.; Zhang, Sean X.

    2014-01-01

    (1-3)-β-d-Glucan (BDG) from cerebrospinal fluid (CSF) is a promising marker for diagnostic and prognostic aid of central nervous system (CNS) fungal infection, but its relationship to serum values has not been studied. Herein, we detected BDG from CSF at levels 2-fold lower than those in serum in patients without evidence of fungal disease but 25-fold higher than those in in serum in noncryptococcal CNS fungal infections. CSF BDG may be a useful biomarker in the evaluation of fungal CNS disea...

  14. Strain-dependent disruption of blood-cerebrospinal fluid barrier by Streptoccocus suis in vitro.

    Science.gov (United States)

    Tenenbaum, Tobias; Adam, Rüdiger; Eggelnpöhler, Ingo; Matalon, David; Seibt, Annette; K Novotny, Gerd E; Galla, Hans-Joachim; Schroten, Horst

    2005-04-01

    Streptococcus suis capsular type 2 is an important agent of diseases including meningitis among pigs worldwide, and is also a zoonotic agent. The barrier function of the choroid plexus epithelium that constitutes the structural basis for the blood-cerebrospinal fluid (CSF) barrier has not been elucidated yet in bacterial meningitis. We investigated the influence of various S. suis isolates on the barrier function of cultured porcine choroid plexus epithelial cells with respect to the transepithelial resistance and paracellular [(3)H]-mannitol flux. Preferentially apical application of S. suis isolates significantly decreased transepithelial resistance and significantly increased paracellular [(3)H]-mannitol flux in a time-, dose- and strain-dependent manner. Viable S. suis isolates caused cytotoxicity determined by lactate dehydrogenase assay and electron microscopy, whereas S. suis sonicates and UV-inactivated S. suis did not cause cytotoxicity. The observed effects on porcine choroid plexus epithelial cells barrier function could not exclusively be ascribed to known virulence factors of S. suis such as suilysin. In conclusion, S. suis isolates induce loss of blood-cerebrospinal fluid barrier function in an in vitro model. Thus, S. suis may facilitate trafficking of bacteria and leucocytes across the blood-cerebrospinal fluid barrier. The underlying mechanisms for the barrier breakdown have yet to be determined. PMID:15780575

  15. Neuron-specific enolase in cerebrospinal fluid and plasma of patients with acute ischemic brain disease

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    Selaković Vesna M.

    2003-01-01

    Full Text Available The objective of this research was to determine the dynamics of change of neuron-specific enolase concentration in patients with acute ischemic brain disease in cerebrospinal fluid and plasma. The study included 103 patients, their mean age 58-66 years. The control group consisted of 16 patients, of matching age and sex, with radicular lesions of discal origin, subjected to diagnostic radiculography. Concentration of neuron-specific enolase was measured by a flouroimmunometric method. The results showed that the concentration of neuron-specific enolase in cerebrospinal fluid and plasma of patients with brain ischemic disease within first seven days significantly increased compared to the control. The highest increase of concentration was established in brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack. Maximal concentration was established on the 3rd-4th day upon the brain infarction. Neuron-specific enolase concentration in cerebrospinal fluid and plasma may be an indicator of pathophysiological processes in the acute phase of brain ischemia and is significant in early diagnostics and therapy of the disease.

  16. Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning

    Directory of Open Access Journals (Sweden)

    Bharti AR

    2016-04-01

    Full Text Available Ajay R Bharti,1 Steven Paul Woods,2 Ronald J Ellis,3 Mariana Cherner,2 Debra Rosario,3 Michael Potter,3 Robert K Heaton,2 Ian P Everall,4 Eliezer Masliah,5 Igor Grant,2 Scott L Letendre1 On behalf of the Translational Methamphetamine AIDS Research Center Group 1Department of Medicine, 2Department of Psychiatry, 3Department of Neurosciences, University of California San Diego, San Diego, CA, USA; 4Department of Psychiatry, University of Melbourne, Victoria, Australia; 5Department of Pathology, University of Californa San Diego, San Diego, CA, USA Background: Human immunodeficiency virus (HIV and methamphetamine use commonly affect neurocognitive (NC functioning. We evaluated the relationships between NC functioning and two fibroblast growth factors (FGFs in volunteers who differed in HIV serostatus and methamphetamine dependence (MAD. Methods: A total of 100 volunteers were categorized into four groups based on HIV serostatus and MAD in the prior year. FGF-1 and FGF-2 were measured in cerebrospinal fluid by enzyme-linked immunosorbent assays along with two reference biomarkers (monocyte chemotactic protein [MCP]-1 and neopterin. Comprehensive NC testing was summarized by global and domain impairment ratings. Results: Sixty-three volunteers were HIV+ and 59 had a history of MAD. FGF-1, FGF-2, and both reference biomarkers differed by HIV and MAD status. For example, FGF-1 levels were lower in subjects who had either HIV or MAD than in HIV– and MAD– controls (P=0.003. Multivariable regression identified that global NC impairment was associated with an interaction between FGF-1 and FGF-2 (model R2=0.09, P=0.01: higher FGF-2 levels were only associated with neurocognitive impairment among subjects who had lower FGF-1 levels. Including other covariates in the model (including antidepressant use strengthened the model (model R2=0.18, P=0.004 but did not weaken the association with FGF-1 and FGF-2. Lower FGF-1 levels were associated with impairment

  17. Levels of soluble delta-like ligand 1 in the serum and cerebrospinal fluid of tuberculous meningitis patients

    Institute of Scientific and Technical Information of China (English)

    Jinghong Li; Jinyi Li; Yanjie Jia

    2012-01-01

    In this study, the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum of 50 patients with tuberculous meningitis, 30 patients with viral meningitis, 20 patients with purulent meningitis and 40 subjects without central nervous system disease were determined using an enzyme-linked immunosorbent assay. The mean levels of soluble delta-like ligand 1 in both cerebrospinal fluid and serum from patients with tuberculous meningitis were significantly higher compared with those from patients with viral meningitis or purulent meningitis or from subjects without central nervous system disease. Meanwhile, the level of soluble delta-like ligand 1 gradually decreased as tuberculous meningitis patients recovered. If patients deteriorated after treatment, the level of soluble delta-like ligand 1 in cerebrospinal fluid gradually increased. There was no correlation between the level of soluble delta-like ligand 1 and the protein level/cell number in cerebrospinal fluid. Our findings in-dicate that the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum are reliable markers for the diagnosis of tuberculous meningitis and for monitoring treatment progress. At the same time, this index is not influenced by protein levels or cell numbers in cerebrospinal fluid.

  18. Increased prothrombin, apolipoprotein A-IV, and haptoglobin in the cerebrospinal fluid of patients with Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Yen-Chu Huang

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion. The need for biomarkers of onset and progression in HD is imperative, since currently reliable outcome measures are lacking. We used two-dimensional electrophoresis and mass spectrometry to analyze the proteome profiles in cerebrospinal fluid (CSF of 6 pairs of HD patients and controls. Prothrombin, apolipoprotein A-IV (Apo A-IV and haptoglobin were elevated in CSF of the HD patients in comparison with the controls. We used western blot as a semi-quantified measurement for prothrombin and Apo A-IV, as well as enzyme linked immunosorbent assay (ELISA for measurement of haptoglobin, in 9 HD patients and 9 controls. The albumin quotient (Qalb, a marker of blood-brain barrier (BBB function, was not different between the HD patients and the controls. The ratios of CSF prothrombin/albumin (prothrombin/Alb and Apo A-IV/albumin (Apo A-IV/Alb, and haptoglobin level were significantly elevated in HD. The ratio of CSF prothrombin/Alb significantly correlated with the disease severity assessed by Unified Huntington's Disease Rating Scale (UHDRS. The results implicate that increased CSF prothrombin, Apo A-IV, and haptoglobin may be involved in pathogenesis of HD and may serve as potential biomarkers for HD.

  19. Coupling poroelasticity and CFD for cerebrospinal fluid hydrodynamics.

    Science.gov (United States)

    Tully, Brett; Ventikos, Yiannis

    2009-06-01

    This research uses a novel coupling of poroelastic theory and computational fluid dynamics to investigate acute hydrocephalus resulting from stenosis of the cerebral aqueduct. By coupling poroelastic theory with a multidimensional simulation of the cerebral aqueduct we are able to investigate, for the first time, the impact of physically relevant stenosis patterns on ventricular enlargement, accounting for the nonintuitive long time history responses of the ventricular system. Preliminary findings demonstrate clearly the importance that the fluidic-poroelastic coupling plays: ventricular enlargement is significantly smaller with local stenosis patterns and almost all of the observable pressure drop occurs across the stenosis. Short timescale effects [O(heartbeat)] are explored and their contribution to the long timescales interrogated. PMID:19304478

  20. Vasopressin content in the cerebrospinal fluid and fluid perfusing cerebral ventricles in rats after the afferent vagus nerve fibres stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    Experiments were carried out on male rats in urethane anaesthesia. Cerebroventricular system was perfused with McIlwain-Rodniht`s solution from lateral ventricles to cerebellomedullary cistern. Both vagus nerves were cut and the central ends of the nerves were electrically stimulated during the collection of the third 30-min portion of perfusing fluid. Vasopressin (AVP) was determined by radioimmunoassay in samples of the cerebrospinal fluid (CSF) (the first portion) and in five successive samples of the perfusing fluid. AVP concentration in the CSF was several times greater than in the fluid perfusing cerebral ventricles. Alternate electrical stimulation of both vagus nerves did not change considerably the release of AVP into the fluid perfusing the cerebral ventricles in rat, although a certain upward tendency could be observed. It seems that only AVP raised in circulating blood and not in CSF, after vagus nerves stimulation may act on the central nervous structures. (author). 37 refs, 3 figs, 1 tab.

  1. The influence of xenogenic cerebrospinal fluid over the parenchyma of rat's lungs after single total irradiation

    Directory of Open Access Journals (Sweden)

    Shatov D.V.

    2014-06-01

    Full Text Available Background. One of the results of negative influence of irradiation is the radiational injury of lungs, which manifests itself by radiational pneumonitis and pulmonary fibrosis. The medicines of phytogenous and animal origin, microelements and synthetic analogs of natural organism protection's substances, high-molecular compounds, vaccines, cytokines and their inductors are used for early therapy of these complications. As one of such remedies one can use the xenogenic cerebrospinal fluid of cows since its usage shows good effects over the system of hematopoiesis at treatment of medullar form of acute radiation sickness. Objective. Studying the influence of xenogenic cerebrospinal fluid over the lung's parenchyma of the rats, which were exposed to single total irradiation. Methods. The research was performed on 48 mature aged (5 months Wistar rats of both sexes. The animals were divided into following groups: the placebo group, the group, which was getting xenogenic cerebrospinal fluid, the irradiated group, which was getting placebo, and the irradiated group, which was getting cerebrospinal fluid. The lungs were later histologically processed and colored by hematoxylin-eosin and picrofucsine. During the microscopy the percentage of the areas with intact parenchyma, emphysema, dystelektases and hemorrhages, and also the intensity of the collagen fibers were estimated. Results. The triple introduction of the xenogenic cerebrospinal fluid to the animals, which were undergone the irradiation, have reduced the percentage of emphysematous areas by 8,86% (р<0,01 and the haemorrhagic areas by 2,44% (р<0,001 at the expense of increase of the percentage of intact parenchyma by 7,21% (р<0,01 and dystelectatic areas by 4,09% (р<0,001. At the tenfold introduction the percentage of the areas with the intact parenchyma has grown by 11,28% (р<0,001 and the percentage of dystelectatic areas by 4,51% (р<0,001, while the emphysematous areas decreased by 14

  2. Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

    Science.gov (United States)

    Ruan, Qingwei; D'Onofrio, Grazia; Sancarlo, Daniele; Greco, Antonio; Yu, Zhuowei

    2016-01-01

    Cognitive frailty (CF) overlaps with early neuropathological alterations associated with aging-related major neurocognitive disorders, including Alzheimer's disease (AD). Fluid biomarkers for these pathological brain alterations allow for early diagnosis in the preclinical stages of AD, and for objective prognostic assessments in clinical intervention trials. These biomarkers may also be helpful in the screening of CF. The present study reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. The selection criteria for potentially suitable fluid biomarkers included: i) Frequent use in studies of fluid-derived markers and ii) evidence of novel measurement techniques for fluid-derived markers. The present study focused on studies that assessed these biomarkers in AD, mild cognitive impairment and non-AD demented subjects. At present, widely used fluid biomarkers include cerebrospinal fluid (CSF), total tau, phosphorylated tau and amyloid-β levels. With the development of novel measurement techniques and improvements in understanding regarding the mechanisms underlying aging-related major neurocognitive disorders, numerous novel biomarkers associated with various aspects of AD neuropathology are being explored. These include specific measurements of Aβ oligomer or monomer forms, tau proteins in the peripheral plasma and CSF, and novel markers of synaptic dysfunction, neuronal damage and apoptosis, neuronal activity alteration, neuroinflammation, blood brain barrier dysfunction, oxidative stress, metabolites, mitochondrial function and aberrant lipid metabolism. The proposed panels of fluid biomarkers may be useful in the early diagnosis of AD, prediction of the progression of AD from preclinical stages to the dementia stage, and the differentiation of AD from non-AD dementia. In combination with physical frailty, the present study surmised that these biomarkers may also be used as biomarkers for CF, thus contribute

  3. Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease.

    Science.gov (United States)

    Samakashvili, Shorena; Ibáñez, Clara; Simó, Carolina; Gil-Bea, Francisco J; Winblad, Bengt; Cedazo-Mínguez, Angel; Cifuentes, Alejandro

    2011-10-01

    Chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC-LIF) was used to investigate D- and L-amino acid contents in cerebrospinal fluid (CSF) samples related to different Alzheimer disease (AD) stages. CSF samples were taken from (i) control subjects (S1 pool), (ii) subjects showing a mild cognitive impairment who remained stable (S2 pool), (iii) subjects showing an mild cognitive impairment that progressed to AD (S3 pool) and (iv) subjects diagnosed with AD (S4 pool). The optimized procedure only needed 10 μL of CSF and it included sample cleaning, derivatization with FITC and chiral-MEKC-LIF separation. Eighteen standard amino acids were baseline separated with efficiencies up to 703,000 plates/m, high sensitivity (LODs in the nM range) and good resolution (values ranging from 2.6 to 9.5). Using this method, L-Arg, L-Leu, L-Gln, γ-aminobutyric acid, L-Ser, D-Ser, L-Ala, Gly, L-Lys, L-Glu and L-Asp were detected in all the CSF samples. S3 and S4 samples (i.e. AD subjects) showed significant lower amounts of L-Arg L-Lys, L-Glu and L-Asp compared to the non-AD S1 and S2 samples, showing in the S4 group the lowest amounts of L-Arg L-Lys, L-Glu and L-Asp. Moreover, γ-aminobutyric acid was significantly higher in AD subjects with the highest amount also found for S4. No significant differences were observed for the rest of amino acids including D-Ser. Based on the obtained chiral-MEKC-LIF data, it was possible to correctly classify all the samples into the four groups. These results demonstrate that the use of enantioselective procedures as the one developed in this work can provide some new light on the investigations of AD, including the discovery of new biomarkers related to different stages of AD.

  4. SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Carlos Cruchaga

    2010-09-01

    Full Text Available Alzheimer's Disease (AD is a complex and multifactorial disease. While large genome-wide association studies have had some success in identifying novel genetic risk factors for AD, case-control studies are less likely to uncover genetic factors that influence progression of disease. An alternative approach to identifying genetic risk for AD is the use of quantitative traits or endophenotypes. The use of endophenotypes has proven to be an effective strategy, implicating genetic risk factors in several diseases, including anemia, osteoporosis and heart disease. In this study we identify a genetic factor associated with the rate of decline in AD patients and present a methodology for identification of other such factors. We have used an established biomarker for AD, cerebrospinal fluid (CSF tau phosphorylated at threonine 181 (ptau(181 levels as an endophenotype for AD, identifying a SNP, rs1868402, in the gene encoding the regulatory sub-unit of protein phosphatase B, associated with CSF ptau(181 levels in two independent CSF series (P(combined = 1.17 x 10(-05. We show no association of rs1868402 with risk for AD or age at onset, but detected a very significant association with rate of progression of disease that is consistent in two independent series (P(combined = 1.17 x 10(-05. Our analyses suggest that genetic variants associated with CSF ptau(181 levels may have a greater impact on rate of progression, while genetic variants such as APOE4, that are associated with CSF Aβ(42 levels influence risk and onset but not the rate of progression. Our results also suggest that drugs that inhibit or decrease tau phosphorylation may slow cognitive decline in individuals with very mild dementia or delay the appearance of memory problems in elderly individuals with low CSF Aβ(42 levels. Finally, we believe genome-wide association studies of CSF tau/ptau(181 levels should identify novel genetic variants which will likely influence rate of progression of

  5. EDA-containing fibronectin levels in the cerebrospinal fluid of children with meningitis.

    Science.gov (United States)

    Pupek, Małgorzata; Jasonek, Jolanta; Kątnik-Prastowska, Iwona

    2013-01-01

    Fibronectin containing an alternatively spliced extra domain A (EDA-FN) participates in diverse biological cell functions, being also directly or indirectly engaged during an inflammatory response to brain injury and/or neuron regeneration. We analyzed FN and EDA-FN isoform levels by ELISA in 85 cerebrospinal fluid samples and 67 plasma samples obtained from children suffering from bacterial or viral meningitis and non-meningitis peripheral inflammation. We have found that the cerebrospinal level of EDA-FN was significantly lower in the bacterial meningitis group than in the viral- and non-meningitis groups. In the patients' plasma, EDA-FN was almost undetectable. The determination of fibronectin containing the EDA segment might be considered as an additional diagnostic marker of bacterial meningitis in children.

  6. EDA-containing fibronectin levels in the cerebrospinal fluid of children with meningitis.

    Science.gov (United States)

    Pupek, Małgorzata; Jasonek, Jolanta; Kątnik-Prastowska, Iwona

    2013-01-01

    Fibronectin containing an alternatively spliced extra domain A (EDA-FN) participates in diverse biological cell functions, being also directly or indirectly engaged during an inflammatory response to brain injury and/or neuron regeneration. We analyzed FN and EDA-FN isoform levels by ELISA in 85 cerebrospinal fluid samples and 67 plasma samples obtained from children suffering from bacterial or viral meningitis and non-meningitis peripheral inflammation. We have found that the cerebrospinal level of EDA-FN was significantly lower in the bacterial meningitis group than in the viral- and non-meningitis groups. In the patients' plasma, EDA-FN was almost undetectable. The determination of fibronectin containing the EDA segment might be considered as an additional diagnostic marker of bacterial meningitis in children. PMID:23884219

  7. Comparison of methods for miRNA extraction from plasma and quantitative recovery of RNA from plasma and cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Melissa A McAlexander

    2013-05-01

    Full Text Available Interest in extracellular RNA has intensified as evidence accumulates that these molecules may be useful as indicators of a wide variety of biological conditions. To establish specific extracellular RNA molecules as clinically relevant biomarkers, reproducible recovery from biological samples and reliable measurements of the isolated RNA are paramount. Towards these ends, careful and rigorous comparisons of technical procedures are needed at all steps from sample handling to RNA isolation to RNA measurement protocols. In the investigations described in this methods paper, RT-qPCR was used to examine the apparent recovery of specific endogenous miRNAs and a spiked-in synthetic RNA from blood plasma samples. RNA was isolated using several widely used RNA isolation kits, with or without the addition of glycogen as a carrier. Kits examined included total RNA isolation systems that have been commercially available for several years and commonly adapted for extraction of biofluid RNA, as well as more recently introduced biofluids-specific RNA methods. Our conclusions include the following: some RNA isolation methods appear to be superior to others for the recovery of RNA from biological fluids; addition of a carrier molecule seems to be beneficial for some but not all isolation methods; and partially or fully quantitative recovery of RNA is observed from increasing volumes of plasma and cerebrospinal fluid.

  8. Minocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study

    Directory of Open Access Journals (Sweden)

    Fuchs Dietmar

    2011-05-01

    Full Text Available Abstract Background Minocycline is a tetracycline antibiotic that has been shown to attenuate central nervous system (CNS lentivirus infection, immune activation, and brain injury in model systems. To initiate assessment of minocycline as an adjuvant therapy in human CNS HIV infection, we conducted an open-labelled pilot study of its effects on cerebrospinal fluid (CSF and blood biomarkers of infection and immune responses in 7 viremic subjects not taking antiretroviral therapy. Results There were no discernable effects of minocycline on CSF or blood HIV-1 RNA, or biomarkers of immune activation and inflammation including: CSF and blood neopterin, CSF CCL2, CSF white blood cell count, and expression of cell-surface activation markers on CSF and blood T lymphocytes and monocytes. Conclusions This pilot study of biological responses to minocycline suggests little potential for its use as adjunctive antiviral or immunomodulating therapy in chronic untreated HIV infection.

  9. Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla.

    Science.gov (United States)

    Stocker, Sean D; Lang, Susan M; Simmonds, Sarah S; Wenner, Megan M; Farquhar, William B

    2015-12-01

    Elevated NaCl concentrations of the cerebrospinal fluid increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or polysynaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to cerebrospinal fluid hypernatremia. Lateral ventricle infusion of 0.15 mol/L, 0.6 mol/L, and 1.0 mol/L NaCl (5 µL/10 minutes) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure, despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the gamma-aminobutyric acid (GABAA) agonist muscimol abolished the sympathoexcitatory response to intracerebroventricular infusion of 1 mol/L NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and arterial blood pressure. Finally, single-unit recordings of spinally projecting RVLM neurons revealed 3 distinct populations based on discharge responses to intracerebroventricular infusion of 1 mol/L NaCl: type I excited (46%; 11/24), type II inhibited (37%; 9/24), and type III no change (17%; 4/24). All neurons with slow conduction velocities were type I cells. Collectively, these findings suggest that acute increases in cerebrospinal fluid NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and arterial blood pressure. PMID:26416846

  10. Multiple sclerosis test or the 4 humors: cerebrospinal fluid serum, tears and saliva

    International Nuclear Information System (INIS)

    4 were studied biological fluids easily accessible to the immune exploration (cerebrospinal fluid, serum, tears and saliva) in 25 patients with Multiple Sclerosis (MS) during a push clinical disease. The level of interleukin-2 receptor soluble (RsIL-2) was significantly increased by at least 3 of these 4 fluids, compared with normal controls. The sensitivity and specificity of its determination for the diagnosis of the condition was higher than other immunochemical parameters, oligoclonal distribution (OD) of immunoglobulin (Ig) light chain imbalance-and-evoked electrophysiological studies. This method is used to establish a more accurate diagnosis of Multiple Sclerosis as well as to monitor its biological activity with nuclear magnetic resonance (NMR) (Author)

  11. Prostaglandin D Synthase Isoforms from Cerebrospinal Fluid Vary with Brain Pathology

    Directory of Open Access Journals (Sweden)

    Michael G. Harrington

    2006-01-01

    Full Text Available Glutathione independent prostaglandin D synthase (Swissprot P41222, PTGDS has been identified in human cerebrospinal fluid and some changes in PTGDS in relation to disease have been reported. However, little is known of the extent that PTGDS isoforms fluctuate across a large range of congenital and acquired diseases. The purpose of this study was to examine changes in PTGDS isoforms in such a population. Spinal fluid from 22 healthy study participants (normal controls with no classifiable neurological or psychiatric diagnosis was obtained and PTGDS isoforms were identified by specific immunostaining and mass spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms in controls consisted of five charge isoforms that were always present and a small number of occasional, low abundance isoforms. A qualitative survey of 98 different people with a wide range of congenital and acquired diseases revealed striking changes. Loss of the control isoforms occurred in congenital malformations of the nervous system. Gain of additional isoforms occurred in some degenerative, most demyelinating and vasculitic diseases, as well as in Creutzfeldt-Jakob disease. A retrospective analysis of published data that quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and Parkinson’s disease compared to controls revealed significant dysregulation. It is concluded that qualitative and quantitative fluctuations of cerebrospinal fluid PTGDS isoforms reflect both major and subtle brain pathophysiology.

  12. OP27ETOPOSIDE PHARMACOKINETICS FOLLOWING INTRA-CEREBROSPINAL FLUID ADMINISTRATION IN PATIENTS WITH LEPTOMENINGEAL METASTASES

    OpenAIRE

    Meijer, Lisethe; Veal, Gareth; Walker, David; Grundy, Richard

    2014-01-01

    INTRODUCTION: Daily intra-cerebrospinal fluid (CSF) etoposide administration regimens are in use, by-passing the blood-brain-barrier and offering higher CSF drug concentrations at 1/30th to 1/340th the dose in conventional systemically administered standard and high dose etoposide regimens, respectively. METHOD: 42 pharmacokinetic samples were obtained from a paediatric (36) and adult patient (6). Etoposide 0.75 mg was administered over 1-2 minutes via the intra-ventricular (IVT) or lumbar ro...

  13. The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

    OpenAIRE

    Bäckryd, Emmanuel

    2015-01-01

    The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacologic...

  14. [Cerebrospinal fluid pressure studies after the intravenous administration of the steroid narcotic, alphaxolone + alphadolone acetate (Althesin)].

    Science.gov (United States)

    Ekhart, E; List, W F; Vadon, P; Oberbauer, R

    1979-09-30

    The effect of alphaxalon + alphadolon-acetate on cerebrospinal fluid pressure (CSFP), mean arterial blood pressure (MPA), heart rate (BMP) and blood gases was investigated in 18 patients. Cerebral perfusion pressure (CPP) was calculated from the difference MAP minus CSFP. Alphaxalon + alphadolon-acetate lowered the normal CSFP and normalized ketamin induced increase of CSFP. Premedication with alphaxalon + alphadolon-acetate delayed the ketamin induced increase of CSFP, which returned to norm after a second dose of alphaxalon + alphadolon-acetate. This effect was seen despite elevation of pCO2 in all patients breathing spontaneously.

  15. Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis

    International Nuclear Information System (INIS)

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis

  16. Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis.

    OpenAIRE

    Karlsson, M.; Hammers, S; Nilsson-Ehle, I; Malmborg, A S; Wretlind, B

    1996-01-01

    Concentrations of doxycycline and penicillin G in serum and cerebrospinal fluid (CSF) were analyzed in 46 patients during treatment for neuroborreliosis. Twenty patients were treated intravenously with penicillin G at 3 g every 6 h (q6h), and 26 patients were treated orally with doxycycline at 200 mg q24h. All samples were collected on day 13 of treatment. The median concentrations of penicillin G in serum were 0.5, 37, and 5.6 micrograms/ml before and 1 and 3 h after drug administration, and...

  17. Rosai Dorfman disease: case with extensive dural involvement and cerebrospinal fluid pleocytosis.

    Science.gov (United States)

    Nalini, Atchayaram; Jitender, Saini; Anantaram, Gudipati; Santosh, Vani

    2012-03-15

    We report a young adult man who presented with chronic raised intracranial tension features and unusually progressive bilateral visual and hearing impairment of 18 months duration. MR imaging showed extensive dural involvement and contiguous orbital and spinal disease. Cerebrospinal fluid demonstrated persistent high lymphocytic pleocytosis. Dural biopsy obtained from posterior cervical approach with C1 arch excision and meningeal biopsy revealed features of classical of Rosai-Dorfman disease. Histiocytes were strongly positive for CD-68 and S-100 proteins. The illness relentlessly progressed with patient developing total deafness and near total blindness at last follow-up. PMID:22029938

  18. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    Science.gov (United States)

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia.

  19. Amino acid composition of cerebrospinal fluid in actue neuroinfections in children.

    Science.gov (United States)

    Buryakova, A V; Sytinsky, I A

    1975-01-01

    A survey of the cerebrospinal fluid (CSF) amino acids, glutamine, and glutamic and gamma-aminobutyric (GABA) acids was made in 168 children, aged 1 to 14 years, with various neurological infections. The glutamic acid and glutamine concentrations in the CSF of children with severe forms of acute serous and bacterial meningitis were about three to four times as great as in controls. The indices returned almost to normal during recovery. GABA is absent in normal CSF, but appeared in the CSF of patients with bacterial meningitis. Its determination may be used as an additional test to differentiate between serous and bacterial meningitis.

  20. Clinical study of radioisotope clearance from the cerebrospinal fluid space using single photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kuchiwaki, H.; Nagasaka, M.; Takada, S.; Ishiguri, H.; Kameyama, H.; Aoyama, Y.

    1989-07-01

    Radioisotope cisternography with statistical analysis was evaluated in 18 patients with suspected hydrocephalus shown by conventional CT, and 4 control patients. Regions of interest were located at cisterna magna, basal cistern, lateral cistern Silvii, interhemispheric cistern, and lateral ventricle using three dimensional SPECT images. A value for constant K was determined for each exponential radioactivity decay curve. On the basis of SPECT-derived K values our patients were grouped into hydrocephalus, nonhydrocephalus, and control patients. Twelve of 14 hydrocephalus patients were treated by shunt operation. Our less-invasive method showed reliable criteria for assessing the cerebrospinal fluid circulation. (orig.).

  1. Cell-free DNA in the Cerebrospinal Fluid under Emotional Stress

    OpenAIRE

    Mariia Zharova; Pavel Umriukhin; Natalia Veiko

    2016-01-01

    Background: Cell free circulating DNA (cfDNA) in blood is known to be a tumor marker however there is no information about its concentration in cerebrospinal fluid (CSF) in control and in emotional stress (ES). The aim of the study was to determine level of cfDNA in CSF of rats with different resistance to stress before and after ES. Methods: A total of 19 male Wistar rats weighing 200-220 g were included in this study. All rats were divided into 2 groups depending on the motor activity: acti...

  2. Transfer of liraglutide from blood to cerebrospinal fluid is minimal in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Christensen, M; Sparre-Ulrich, A H; Hartmann, B;

    2015-01-01

    -terminus of the GLP-1 moiety of liraglutide. Mean plasma liraglutide was 31 (range: 21-63) nmol l(-1). The mean CSF-liraglutide concentration was 6.5 (range: 0.9-13.9) pmol l(-1). Ratio of CSF: plasma-liraglutide concentrations was 0.02 (range: 0.07-0.002)% and plasma liraglutide did not correlate with CSF......Treatment with liraglutide leads to weight loss. We investigated whether blood-to-cerebrospinal fluid (CSF) transfer of liraglutide occurs, and if so, whether it associates with clinical weight loss following liraglutide treatment in humans. We performed lumbar puncture and blood sampling in eight...

  3. Cerebrospinal fluid flow in empty sella syndrome and normal sellar regions measured by phase-contrast quantitative magnetic resonance

    Institute of Scientific and Technical Information of China (English)

    Weidong Hu; Li Xiang; Xiurong Wang

    2011-01-01

    We used MRI to examine 38 healthy females and 38 female patients with empty sella syndrome. Cerebrospinal fluid flow was examined in six regions of interest, including the anterior clinoid processes, posterior clinoid processes, and 1.0 mm, -1.0 mm, 2.0 mm, -2.0 mm from the midpoint of the line between the anterior and posterior clinoid processes. The results revealed no significant differences in cerebrospinal fluid flow velocity and discharge in a single cardiac cycle, or indicators of cardiac cycles in the control group, indicating that the cerebrospinal fluid flow was relatively steady in the saddle area of the normal brain. In the empty sella syndrome group, cerebrospinal fluid hernia into the saddle area triggered a fluctuation of the anterior and posterior clinoid processes in the saddle area, while the flow in other regions in the saddle area was relatively steady; this resulted in significant differences in cerebrospinal fluid flow velocity and discharge, as well as the cardiac cycle.

  4. Determination of the phosphorylated neurofilament subunit NF-H (pNF-H in cerebro-spinal fluid as biomarker in acute traumatic spinal cord injuries / Dozarea neurofilamentelor fosforilate (subunitatea pNF-H ȋn LCR ca biomarker ȋn traumatismul vertebro-medular acut

    Directory of Open Access Journals (Sweden)

    Ungureanu Didona

    2014-09-01

    Full Text Available Obiectivul studiului. Obiectivul acestui studiu a fost dozarea neurofilamentelor fosforilate (subunitatea pNF-H în lichidul cefalorahidian al pacienţilor cu leziuni traumatice ale măduvei spinării şi stabilirea unei corelaţii intre valoarea pNF-H şi gravitatea leziunilor medulare. Material şi metode. Studiul a inclus 15 pacienţi cu leziuni traumatice acute medulare: opt pacienţi cu leziuni medulare complete şi şapte pacienţi cu leziuni medulare incomplete. Gravitatea leziunilor medulare a fost apreciată folosind scala ASIA (American Spinal Injury Association scale şi la toti pacientii s-a aplicat tratamentul chirurgical în primele 24 de ore (decompresiune medulară şi stabilizare vertebrală. S-a facut determinarea zilnică a pNF-H din LCR folosind testul ELISA specific şi am corelat aceste valori cu evoluţia clinică. Rezultate. Subunitatea pNF-H a fost evidenţiată în LCR la toţi pacienţii cu traumatisme acute vertebro-medulare şi valorile au fost diferite în cazurile leziunilor medulare complete faţa de leziunile incomplete. Nivelul pNF-H din LCR a fost de zece până la o sută de ori mai mare în leziunile medulare complete fata de cazurile cu leziuni incomplete, unde nivelul acestui biomarker a fost aproape normal. Pacienţii cu o evoluţie neurologică favorabilă după tratament au avut un model specific al valorilor zilnice de pNF-H: o creştere bruscă până la o valoare maximă apoi o scădere progresivă până la normal. Valorile maxime au fost diferite în fiecare caz, de 10 ori până la 170 de ori mai mari faţă de normal. Concluzii. Forma fosforilată a subunităţii neurofilamentelor cu greutate moleculară mare pNF-H din lichidul cefalorahidian poate fi un biomarker specific pentru leziunile acute traumatice ale măduvei spinării corelat cu severitatea leziunilor medulare. pNF-H pare a fi un biomarker predictiv deoarece modelul evolutiv al valorilor sale arată reducerea sau blocarea leziunilor

  5. Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Shirin FARIVAR*

    2015-01-01

    Full Text Available How to Cite This Article: : Farivar S, Mohamadzade Z, Shiari R, Fahimzad AR. Neural Differentiation of Human Umbilical CordMesenchymal Stem Cells by Cerebrospinal Fluid. . Iran J Child Neurol. 2015 Winter; 9(1:87-93.  Abstract Objective Wharton’s jelly (WJ is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF on neural differentiation of human WJ stem cells.Material & Methods The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2, and Glial Fibrillary Astrocytic Protein (GFAP for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR.Results Treatment with 100 and 200μg/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer.Conclusion RT-PCR showed that

  6. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy;

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...

  7. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    Science.gov (United States)

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  8. Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    J.E. Lima

    2006-01-01

    Full Text Available The clinical manifestations of neurocysticercosis (NC are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D, 8 patients with viable cysts (V and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5 or cerebrospinal fluid (P = 0.91 S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.

  9. A Rare Case of Spontaneous Pneumocephalus Associated with Nontraumatic Cerebrospinal Fluid Leak

    Directory of Open Access Journals (Sweden)

    Murad Baba

    2016-01-01

    Full Text Available Introduction. Spontaneous nontraumatic pneumocephalus (PNC and cerebrospinal fluid (CSF leaks are both very uncommon conditions. We report a rare case of spontaneous pneumocephalus associated with CSF leak secondary to right sphenoid sinus bony defect without history of trauma. Case Description. 51-year-old Hispanic female with past medical history of hypertension and idiopathic intracranial hypertension (Pseudotumor Cerebri presented to the emergency room complaining of headache and clear discharge from the right nostril. Physical examination was significant for right frontal sinus tenderness and clear discharge from right nostril. Computed Tomography (CT scan of the brain showed moderate amount of extra-axial air within the right cerebral hemisphere indicative of pneumocephalus. CT scan of facial bones showed bony defect along the right sphenoid sinus with abnormal CSF collection. The patient was started on intravenous antibiotics for meningitis prophylaxis and subsequently underwent transsphenoidal repair of cerebrospinal fluid leak with abdominal fat graft. CSF rhinorrhea stopped completely after the surgery with near complete resolution of pneumocephalus before discharge. Conclusions. Early identification of pneumocephalus and surgical intervention can help decrease the morbidity and avoid possible complications. Idiopathic intracranial hypertension, although rare, can lead to CSF leak and pneumocepahlus.

  10. Embryonic cerebrospinal fluid collaborates with the isthmic organizer to regulate mesencephalic gene expression.

    Science.gov (United States)

    Parada, Carolina; Martín, Cristina; Alonso, María I; Moro, José A; Bueno, David; Gato, Angel

    2005-11-01

    Early in development, the behavior of neuroepithelial cells is controlled by several factors acting in a developmentally regulated manner. Recently it has been shown that diffusible factors contained within embryonic cerebrospinal fluid (CSF) promote neuroepithelial cell survival, proliferation, and neurogenesis in mesencephalic explants lacking any known organizing center. In this paper, we show that mesencephalic and mesencephalic+isthmic organizer explants cultured only with basal medium do not express the typically expressed mesencephalic or isthmic organizer genes analyzed (otx2 and fgf8, respectively) and that mesencephalic explants cultured with embryonic CSF-supplemented medium do effect such expression, although they exhibit an altered pattern of gene expression, including ectopic shh expression domains. Other trophic sources that are able to maintain normal neuroepithelial cell behavior, i.e., fibroblast growth factor-2, fail to activate this ectopic shh expression. Conversely, the expression pattern of the analyzed genes in mesencephalic+isthmic organizer explants cultured with embryonic cerebrospinal fluid-supplemented medium mimics the pattern for control embryos developed in ovo. We demonstrate that embryonic CSF collaborates with the isthmic organizer in regulation of the expression pattern of some characteristic neuroectodermal genes during early stages of central nervous system (CNS) development, and we suggest that this collaboration is not restricted to the maintenance of neuroepithelial cell survival. Data reported in this paper corroborate the hypothesis that factors contained within embryonic CSF contribute to the patterning of the CNS during early embryonic development. PMID:16180222

  11. EFFECTS OF ACUPUNCTURE ON AMINO ACID CONTENTS IN CEREBROSPINAL FLUID AFTER BRAIN INJURY

    Institute of Scientific and Technical Information of China (English)

    CHEN Wei; KE Xue-hong; HU Peng; YANG Xue-ping

    2006-01-01

    Objective To probe into the mechanism on acupuncture treatment for brain injury. Methods Thirty cases of acute craniocerebral injury were divided into two groups according to the sequence of visiting.In the control (15cases), the routine western medicine was applied. In the experimental group (15 cases),(Asp), glutamic acid (Glu) and γ-amino butyric acid (GABA) were observed successively and the relevant analysis was done. Results There was no significant difference in the concentrations of Asp, Glu and GABA before and on the 1st day after the treatment between two groups (P>0.05). The difference had not been presented between the concentrations on the 1st day and before the treatment. But, the difference was significant or very significant between the concentrations on the 5th days and before the treatment (P<0.05,P < 0.01 ). In the experimental group, the concentration of Asp in the cerebrospinal fluid was lower obviously compared with that in the control (P<0.05) and the concentration of GABA was higher compared with the control (P < 0.01). Conclusion Acupuncture lowered the contents of Asp and Glu and increased the level of GABA in the cerebrospinal fluid rapidly so that the excitation and inhibition in the nervous system could be rebalanced. It was further indicated that acupuncture worked on the treatment of craniocerebral injury.

  12. Effect of continuous cisternal cerebrospinal fluid drainage for patients with thin subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Yasunari Otawara

    2007-09-01

    Full Text Available Yasunari Otawara, Kuniaki Ogasawara, Yoshitaka Kubo, Masayuki Sasoh, Akira OgawaDepartment of Neurosurgery, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, JapanAbstract: External cerebrospinal fluid (CSF drainage is an effective method to remove massive subarachnoid hemorrhage (SAH, but carries the risk of meningitis and shunt-dependent hydrocephalus. This study investigated whether postoperative cisternal CSF drainage affects the incidence of cerebral vasospasm and clinical outcome in patients with thin SAH. Seventy-eight patients with thin SAH, 22 men and 56 women aged from 17 to 73 years (mean 51.2 years, underwent surgical repair for ruptured anterior circulation aneurysm. Patients were divided into groups with (38 patients and without (40 patients postoperative cisternal CSF drainage, and the incidences of angiographical and symptomatic vasospasm, shunt-dependent hydrocephalus, meningitis, and the clinical outcome were compared. The incidences of angiographical vasospasm (31.6% vs 50.0%, symptomatic vasospasm (7.9% vs 12.5%, shunt-dependent hydrocephalus (5.3% vs 0%, and meningitis (2.6% vs 0% did not differ between patients with and without cisternal CSF drainage. All patients in both groups resulted in good recovery. Postoperative cisternal CSF drainage does not affect the incidence of cerebral vasospasm or the clinical outcome in patients with thin SAH.Keywords: subarachnoid hemorrhage; cerebrospinal fluid drainage; cerebral vasospasm; meningitis; hydrocephalus; ruptured intracranial aneurysm

  13. Cerebrospinal fluid prohormone processing and neuropeptides stimulating feed intake of dairy cows during early lactation.

    Science.gov (United States)

    Kuhla, Björn; Laeger, Thomas; Husi, Holger; Mullen, William

    2015-02-01

    After parturition, feed intake of dairy cows increases within the first weeks of lactation, but the molecular mechanisms stimulating or delaying the slope of increase are poorly understood. Some of the molecules controlling feed intake are neuropeptides that are synthesized as propeptides and subsequently processed before they bind to specific receptors in feeding centers of the brain. Cerebrospinal fluid surrounds most of the feed intake regulatory centers and contains numerous neuropeptides. In the present study, we used a proteomic approach to analyze the neuropeptide concentrations in cerebrospinal fluid taken from dairy cows between day -18 and -10, and between day +10 and +20 relative to parturition. We found 13 proteins which were only present in samples taken before parturition, 13 proteins which were only present in samples taken after parturition, and 25 proteins which were commonly present, before and after parturition. Among them, differences in pro-neuropeptide Y, proenkephalin-A, neuroendocrine convertase-2, neurosecretory protein VGF, chromogranin-A, and secretogranin-1 and -3 concentrations relative to parturition highlight propeptides and prohormone processings involved in the control of feed intake and energy homeostasis. Scaffold analysis further emphasized an increased tone of endogenous opioids associated with the postparturient increase of feed intake.

  14. Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model

    Institute of Scientific and Technical Information of China (English)

    Haisheng Liu; Zhili Ni; Yetao Chen; Dong Wang; Yan Qi; Qiuhang Zhang; Shijie Wang

    2012-01-01

    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil(R) (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.

  15. Identification of Oropouche Orthobunyavirus in the cerebrospinal fluid of three patients in the Amazonas, Brazil.

    Science.gov (United States)

    Bastos, Michele de Souza; Figueiredo, Luiz Tadeu Moraes; Naveca, Felipe Gomes; Monte, Rossicleia Lins; Lessa, Natália; Pinto de Figueiredo, Regina Maria; Gimaque, João Bosco de Lima; Pivoto João, Guilherme; Ramasawmy, Rajendranath; Mourão, Maria Paula Gomes

    2012-04-01

    Oropouche fever is the second most frequent arboviral infection in Brazil, surpassed only by dengue. Oropouche virus (OROV) causes large and explosive outbreaks of acute febrile illness in cities and villages in the Amazon and Central-Plateau regions. Cerebrospinal fluid (CSF) samples from 110 meningoencephalitis patients were analyzed. The RNA extracted from fluid was submitted to reverse transcription-polymerase chain reaction and sequencing to identify OROV. Three CSF samples showed the presence of OROV causing infection in the central nervous system (CNS). These patients are adults. Two of the patients had other diseases affecting CNS and immune systems: neurocysticercosis and acquired immunodeficiency syndrome, respectively. Nucleotide sequence analysis showed that the OROV from the CSF of these patients belonged to genotype I. We show here that severe Oropouche disease is occurring during outbreaks of this virus in Brazil.

  16. Phosphorylated tau/amyloid beta 1-42 ratio in ventricular cerebrospinal fluid reflects outcome in idiopathic normal pressure hydrocephalus

    Directory of Open Access Journals (Sweden)

    Patel Sunil

    2012-03-01

    Full Text Available Abstract Background Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible cause of dementia and gait disturbance that is typically treated by operative placement of a ventriculoperitoneal shunt. The outcome from shunting is variable, and some evidence suggests that the presence of comorbid Alzheimer's disease (AD may impact shunt outcome. Evidence also suggests that AD biomarkers in cerebrospinal fluid (CSF may predict the presence of AD. The aim of this study was to investigate the relationship between the phosphorylated tau/amyloid beta 1-42 (ptau/Aβ1-42 ratio in ventricular CSF and shunt outcome in patients with iNPH. Methods We conducted a prospective trial with a cohort of 39 patients with suspected iNPH. Patients were clinically and psychometrically assessed prior to and approximately 4 months after ventriculoperitoneal shunting. Lumbar and ventricular CSF obtained intraoperatively, and tissue from intraoperative cortical biopsies were analyzed for AD biomarkers. Outcome measures included performance on clinical symptom scales, supplementary gait measures, and standard psychometric tests. We investigated relationships between the ptau/Aβ1-42 ratio in ventricular CSF and cortical AD pathology, initial clinical features, shunt outcome, and lumbar CSF ptau/Aβ1-42 ratios in the patients in our cohort. Results We found that high ptau/Aβ1-42 ratios in ventricular CSF correlated with the presence of cortical AD pathology. At baseline, iNPH patients with ratio values most suggestive of AD presented with better gait performance but poorer cognitive performance. Patients with high ptau/Aβ1-42 ratios also showed a less robust response to shunting on both gait and cognitive measures. Finally, in a subset of 18 patients who also underwent lumbar puncture, ventricular CSF ratios were significantly correlated with lumbar CSF ratios. Conclusions Levels of AD biomarkers in CSF correlate with the presence of cortical AD pathology

  17. Studies on homocarnosine in cerebrospinal fluid in infancy and childhood. Part II. Homocarnosine levels in cerebrospinal fluid from children with epilepsy, febrile convulsion or meningitis.

    Science.gov (United States)

    Takahashi, H

    1981-01-01

    To clarify the pathophysiological role of homocarnosine in the cerebrospinal fluid (CSF) in children, homocarnosine levels in CSF were determined in patients with epilepsy (32 cases), febrile convulsion (5 cases) and meningitis (42 cases) with a high speed amino acid autoanalyzer (Hitachi Co.). Mean homocarnosine levels in CSF of controlled epileptic children, uncontrolled epileptic children and febrile convulsion cases were 0.61 +/- 0.25 mumol/dl, 1.03 +/- 0.37 mumol/dl and 1.09 +/- 0.04 mumol/dl, respectively. High homocarnosine levels in CSF of children with uncontrolled epilepsy or febrile convulsion may indicate the reduced turnover rate from homocarnosine to GABA. In patients with meningitis, the unconscious states were accompanied by significantly lower homocarnosine levels in CSF (0.39 +/- 0.20 mumol/dl) than those in the patients with clear conscious states (0.9 +/- 0.31 mumol/dl, however, in patients with clear conscious states homocarnosine in CSF were almost the same as those of normal children (0.89 +/- 0.23 mumol/dl). These data suggest that homocarnosine in CSF might be related to the convulsive tendency and consciousness. PMID:7283086

  18. Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets

    Science.gov (United States)

    Barone, Francesca; Elmi, Alberto; Romagnoli, Noemi; Bacci, Maria Laura

    2016-01-01

    When it comes to neuroscience, pigs represent an important animal model due to their resemblance with humans’ brains for several patterns including anatomy and developmental stages. Cerebrospinal fluid (CSF) is a relatively easy-to-collect specimen that can provide important information about neurological health and function, proving its importance as both a diagnostic and biomedical monitoring tool. Consequently, it would be of high scientific interest and value to obtain more standard physiological information regarding its composition and dynamics for both swine pathology and the refinement of experimental protocols. Recently, proton nuclear magnetic resonance (1H NMR) spectroscopy has been applied in order to analyze the metabolomic profile of this biological fluid, and results showed the technique to be highly reproducible and reliable. The aim of the present study was to investigate in both qualitative and quantitative manner the composition of Cerebrospinal Fluid harvested form healthy newborn (5 days old-P5) and young (30-P30 and 50-P50 days old) piglets using 1H NMR Spectroscopy, and to analyze any possible difference in metabolites concentration between age groups, related to age and Blood-Brain-Barrier maturation. On each of the analyzed samples, 30 molecules could be observed above their limit of quantification, accounting for 95–98% of the total area of the spectra. The concentrations of adenine, tyrosine, leucine, valine, 3-hydroxyvalerate, 3-methyl-2-oxovalerate were found to decrease between P05 and P50, while the concentrations of glutamine, creatinine, methanol, trimethylamine and myo-inositol were found to increase. The P05-P30 comparison was also significant for glutamine, creatinine, adenine, tyrosine, leucine, valine, 3-hydroxyisovalerate, 3-methyl-2-oxovalerate, while for the P30-P50 comparison we found significant differences for glutamine, myo-inositol, leucine and trimethylamine. None of these molecules showed at P30 concentrations

  19. Intracranial pressure, its components and cerebrospinal fluid pressure-volume compensation.

    Science.gov (United States)

    Kasprowicz, M; Lalou, D A; Czosnyka, M; Garnett, M; Czosnyka, Z

    2016-09-01

    Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant-rate infusion study. Due to the dynamic nature of ICP, a 'snapshot' manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure-volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction. PMID:26666840

  20. Do genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia.

    Directory of Open Access Journals (Sweden)

    Joana A Palha

    2012-08-01

    Full Text Available Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus, the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF. Enlarged brain ventricles are already present at the time of disease onset (young adulthood and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that an altered choroid plexus/CSF dynamics during neurodevelopment may be considered as a risk, causative and/or participating-key factor for development of schizophrenia.

  1. Knowledge-base for interpretation of cerebrospinal fluid data patterns. Essentials in neurology and psychiatry.

    Science.gov (United States)

    Reiber, Hansotto

    2016-06-01

    The physiological and biophysical knowledge base for interpretations of cerebrospinal fluid (CSF) data and reference ranges are essential for the clinical pathologist and neurochemist. With the popular description of the CSF flow dependent barrier function, the dynamics and concentration gradients of blood-derived, brain-derived and leptomeningeal proteins in CSF or the specificity-independent functions of B-lymphocytes in brain also the neurologist, psychiatrist, neurosurgeon as well as the neuropharmacologist may find essentials for diagnosis, research or development of therapies. This review may help to replace the outdated ideas like "leakage" models of the barriers, linear immunoglobulin Index Interpretations or CSF electrophoresis. Calculations, Interpretations and analytical pitfalls are described for albumin quotients, quantitation of immunoglobulin synthesis in Reibergrams, oligoclonal IgG, IgM analysis, the polyspecific ( MRZ- ) antibody reaction, the statistical treatment of CSF data and general quality assessment in the CSF laboratory. The diagnostic relevance is documented in an accompaning review. PMID:27332077

  2. Comparison of Three Nucleic Acid Amplification Assays of Cerebrospinal Fluid for Diagnosis of Cytomegalovirus Encephalitis

    Science.gov (United States)

    Bestetti, Arabella; Pierotti, Chiara; Terreni, Mariarosa; Zappa, Alessandra; Vago, Luca; Lazzarin, Adriano; Cinque, Paola

    2001-01-01

    The diagnostic reliabilities of three cytomegalovirus (CMV) nucleic acid amplification assays of cerebrospinal fluid (CSF) were compared by using CSF samples from human immunodeficiency virus-infected patients with a postmortem histopathological diagnosis of CMV encephalitis (n = 15) or other central nervous system conditions (n = 16). By using a nested PCR assay, the quantitative COBAS AMPLICOR CMV MONITOR PCR, and the NucliSens CMV pp67 nucleic acid sequence-based amplification assay, sensitivities were 93.3, 86.6, and 93.3%, respectively, and specificities were 93.7, 93.7, and 87.5%, respectively. The COBAS AMPLICOR assay revealed significantly higher CMV DNA levels in patients with diffuse ventriculoencephalitis than in patients with focal periventricular lesions. PMID:11230445

  3. Endoscopic repair of spontaneous cerebro-spinal fluid rhinorrhoea: a report of 3 cases.

    Science.gov (United States)

    Gendeh, B S; Wormald, P J; Forer, M; Goh, B S; Misiran, K

    2002-12-01

    Three cases of spontaneous Cerebrospinal Fluid (CSF) rhinorrhea were managed at the National University Hospital, Kuala Lumpur. Case 1 had bilateral leak secondary to empty sella syndrome and the rest two cases had unilateral leak. Four transnasal endoscopic approaches were performed on these three cases since March 1999. The role of intrathecal Sodium Fluorescein is highlighted in localising the CSF fistula. Case 3 required postoperative lumbar drain as an adjunct. No recurrent leak was noted on post operative follow up in Case 2 and 3 ranging from nine to thirty two months. A recurrent left leak at six months was noted in Case 1 which could likely be due to her sudden bout of cough attacks and patient refused further surgical intervention. PMID:12733180

  4. Lower levels of cerebrospinal fluid amyloid beta (Abeta) in non-demented Indian controls.

    Science.gov (United States)

    Subramanian, Sarada; Sandhyarani, Boya; Shree, A N Divya; Murthy, K Krishna; Kalyani, K; Kumar, S Praveen; Pradeep; Noone, Mohin Jeslie; Taly, A B

    2006-10-23

    Prevalence of Alzheimer's disease in Indian population is lower than in developed countries. To determine whether limitation of amyloid beta (Abeta) concentration may be responsible for lower rate of incidence, we measured the levels of Abeta in cerebrospinal fluid (CSF) collected from 72 non-demented individuals ranging in the age from 20 years to 65 years. These samples were segregated into three groups ranging from 20-35 years, 36-50 years and 51-65 years of age. Levels of Abeta could be detected in all the age groups and they were much lower than the values reported in literature from the developed countries. No significant difference in the average level of Ass was observed with increase in age. PMID:16978775

  5. Immunological studies of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination.

    Science.gov (United States)

    Takahashi, Yukitoshi; Matsudaira, Takashi; Nakano, Hitoshi; Nasu, Hirosato; Ikeda, Hitoshi; Nakaoka, Kentaro; Takayama, Rumiko; Oota, Masayasu

    2016-09-15

    In 32 patients with prolonged central nervous system symptoms after human papillomavirus (HPV) vaccination, we measured conventional and immunological markers in cerebrospinal fluid (CSF) and compared with the levels in disease controls. Our studies revealed significantly decreased chloride and neuron-specific enolase (NSE) levels in CSF of patients with CNS symptoms after HPV vaccination compared to disease controls. IL-4, IL-13, and CD4(+) T cells increased significantly in patients, and IL-17 increased significantly from 12 to 24months after symptom onset. Chemokines (IL-8 and MCP-1) were also elevated, but CD8(+) T cells, PDGF-bb and IL-12 were reduced. Antibodies to GluN2B-NT2, GluN2B-CT and GluN1-NT increased significantly. These results suggest biological, mainly immunological, changes in the CSF of patients after HPV vaccination. PMID:27609278

  6. A Window into the Heterogeneity of Human Cerebrospinal Fluid Aβ Peptides

    Directory of Open Access Journals (Sweden)

    Roberta Ghidoni

    2011-01-01

    Full Text Available The initiating event in Alzheimer's disease (AD is an imbalance in the production and clearance of amyloid beta (Aβ peptides leading to the formation of neurotoxic brain Aβ assemblies. Cerebrospinal Fluid (CSF, which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF Aβ peptides. Specifically, we focused our attention on the heterogeneity of the CSF Aβ world discussing (1 basic research studies and what has been translated to clinical practice, (2 monomers and other soluble circulating Aβ assemblies, and (3 communication modes for Aβ peptides and their microenvironment targets. Finally, we suggest that Aβ peptides as well as other key signals in the central nervous system (CNS, mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function.

  7. MR imaging of multiple sclerosis in patients with negative cerebrospinal fluid

    International Nuclear Information System (INIS)

    A prospective study was performed to assess the value of MR imaging for detecting demyelinating disease of the brain in 50 patients with clinically suspected multiple sclerosis but negative cerebrospinal fluid (CSF). The MR imaging examinations were performed with a superconducting magnet (Philips Gyroscan S15) operating at 0.5T. A multisection, double spin-echo technique was used in all cases (TR = 2,100 msec, TE = 50 and 100 msec). No abnormality was demonstrated in eight patients. In the others, lesions were usually located in the periventricular white matter (rounded masses and/or high signal intensity bands along the lateral ventricles), the brain stem and thalami (12 patients), and the cerebellum (6 patients). In conclusion, MR imaging appears to be an exquisite imaging modality for confirmation of clinically suspected multiple sclerosis in patients with negative CSF. However, it must include examination of the spinal cord when the brain examination is negative

  8. YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis

    DEFF Research Database (Denmark)

    Ostergaard, C; Johansen, JS; Benfield, Thomas;

    2002-01-01

    cerebrospinal fluid (CSF) samples taken on admission from patients suspected of having meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were significantly higher in patients with purulent meningitis (median......, 663 microg/liter [range, 20 to 8,960]) and encephalitis (5,430 microg/liter [620 to 11,600]) than in patients with lymphocytic meningitis (137 microg/liter [41 to 1,865]) or patients without meningitis (167 microg/liter [24 to 630]) (Kruskal-Wallis and Dunn multiple comparison tests, P ... YKL-40 levels were also determined for 26 patients with purulent meningitis having a repuncture, and patients who died (n = 5) had significantly higher YKL-40 levels than patients who survived (n = 21) (2,100 microg/liter [1,160 to 7,050] versus 885 microg/liter [192 to 15,400], respectively; Mann...

  9. The influence of preanalytical conditions on the DJ-1 concentration in human cerebrospinal fluid

    DEFF Research Database (Denmark)

    Salvesen, Lisette; Tanassi, Julia T; Bech, Sara;

    2014-01-01

    AIM: The purpose of this study was to establish the influence of centrifugation and protease activity on the cerebrospinal fluid (CSF) concentrations of DJ-1 and hemoglobin. MATERIALS & METHODS: The concentrations of DJ-1 and hemoglobin were determined in 12 (DJ-1) and six (hemoglobin) pairs of CSF...... samples, with one sample being stored without centrifugation and the other being centrifuged at 2000 × g before storage. The DJ-1 concentration was also determined in centrifuged and uncentrifuged CSF containing protease inhibitors and compared with values determined in centrifuged and uncentrifuged CSF...... samples without protease inhibitors. Furthermore, specific protein concentrations were determined in CSF from two groups, each comprising 23 patients with Parkinson's disease. In one group the CSF was centrifuged at 1300-1800 × g, 4°C, 10 min, and in the other at 2000 × g, 4°C, 10 min. RESULTS...

  10. A Case of Hypogammaglobulinemia with Enteroviral Meningoencephalitis, Associated with Increased Adenosine Deaminase in Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Alborizi Abdolvahab

    2009-06-01

    Full Text Available We describe the development of enterovirus meningoencephalitis associated with increased adenosine deaminase in cerebrospinal fluid of a 12-year-old boy, a known case of hypogamaglobulinemia despite monthly replacement of IVIg.The patient was referred to our center with fever, headache and vomiting for 10 days. CSF analysis was compatible with aseptic meningoencephalitis but high CSF protein (>200mg/dl and high level of adenosine deaminase in CSF (30IU/L were against the diagnosis of simple viral meningoencephalitis. Nested PCR of CSF for entrovirus was positive. Treatment with daily high-dose IVIg was commenced, with significant clinical improvement. For patients with increased ADA and lymphocytic pleocytosis in CSF, differential diagnoses should include enteroviral meningitis. Antibodies, although crucial, cannot on their own prevent enteroviral infection in some hypogamaglbulinemic patients.

  11. Kinetics of HIV-1 in cerebrospinal fluid and plasma in cryptococcal meningitis

    Directory of Open Access Journals (Sweden)

    Jorge A. Benetucci

    2012-04-01

    Full Text Available In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF and plasma in patients with cryptococcal meningitis (CM, we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy- free HIV-infected patients with CM. Samples were obtained at baseline (S1 and at the second (S2 and third (S3 weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease.

  12. Association of Brucella Meningoencephalitis with Cerebrospinal Fluid Shunt in A Child: A Case Report

    Directory of Open Access Journals (Sweden)

    Babak ABDINIA

    2013-01-01

    Full Text Available Brucellosis is an endemic zoonosis in Iran. It is a systemic infection that can involve any organs or systems of the body and have variable presentations. Ventriculoperitoneal (VP shunt infections due to brucellosis have been rarely reported in the literatures.This is the history of a four years old boy who developed Brucella meningoencephalitis at the age of 42 months, whilst he had a VP shunt in situ for hydrocephalus treatment. Also, he presented brucellosis as acute abdomen. This patient was treated with trimethoprim-sulfamethoxazole, gentamicin and rifampicin. The shunt was extracted and all clinical and laboratory test abnormalities subsided through this management.We propose that in a patient with Brucella meningoencephalitis, the cerebrospinal fluid shunt system can be extracted and treatment with appropriate combination of antibiotics could be successful. Moreover, it shows that brucellosis should be considered in the differential diagnosis for acute abdomen and ascites in endemic regions.

  13. Failure of droperidol and ketamine to influence cerebrospinal fluid production in the dog.

    Directory of Open Access Journals (Sweden)

    Ikeda,Shigemasa

    1983-12-01

    Full Text Available Using the ventriculo-cisternal perfusion method, the effects of droperidol and ketamine hydrochloride on cerebrospinal fluid (CSF production were studied in dogs. Neither droperidol (0.25 mg/kg, IV nor ketamine (3 mg/kg, IV caused a statistically significant change in CSF production rate. Positive correlation between CSF production and corresponding cerebral perfusion pressure (CPP was observed in the ketamine study, whose unfavorable effect on neurosurgical anaesthesia would be obvious. On the other hand droperidol (0.25 mg/kg, IV tended to decrease CSF production. Droperidol alone or in combination with other analgesics such as fentanyl as currently used in neurosurgical anaesthesia appears to be an appropriate choice in patients with increased intracranial pressure.

  14. [Chromatographic analysis of low molecular weight fraction of cerebrospinal fluid in children with acute neuroinfections].

    Science.gov (United States)

    Alekseeva, L A; Shatik, S V; Sorokina, M N; Karasev, V V

    2002-05-01

    Low molecular-weight (oligopeptide) fraction of the cerebrospinal fluid was analyzed by high-performance reversed phase liquid chromatography in 30 children with bacterial and viral neuroinfections. The incidence and height of chromathoraphic peaks in bacterial meningitis depended on the disease etiology, stage, and severity. Qualitative and quantitative composition of low molecular-weight fraction of the liquor varied in patients with viral neuroinfections, depending on the severity of the cerebral parenchyma involvement. Differences in chromatographic profiles in complicated and uneventful course of neuroinfections indicate a possible damaging, protective, or regulatory effect of the liquor peptides. These data focus the attention on the role of oligopeptides in the genesis of neuroinfectious process, significance of search for peptide markers, their further isolation, identification, and development of test systems available for clinical application.

  15. Automated quantification technology for cerebrospinal fluid dynamics based on magnetic resonance image analysis

    International Nuclear Information System (INIS)

    Time-spatial labeling inversion pulse (Time-SLIP) technology, which is a non-contrast-enhanced magnetic resonance imaging (MRI) technology for the visualization of blood flow and cerebrospinal fluid (CSF) dynamics, is used for diagnosis of neurological diseases related to CSF including idiopathic normal-pressure hydrocephalus (iNPH), one of the causes of dementia. However, physicians must subjectively evaluate the velocity of CSF dynamics through observation of Time-SLIP images because no quantification technology exists that can express the values numerically. To address this issue, Toshiba, in cooperation with Toshiba Medical Systems Corporation and Toshiba Rinkan Hospital, has developed an automated quantification technology for CSF dynamics utilizing MR image analysis. We have confirmed the effectiveness of this technology through verification tests using a water phantom and quantification experiments using images of healthy volunteers. (author)

  16. Multiple simultaneous intracerebral hemorrhages following accidental massive lumbar cerebrospinal fluid drainage: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Ruiz-Sandoval Jose

    2006-01-01

    Full Text Available Multiple simultaneous intracerebral hemorrhages (ICH are uncommon. We report the case of an 80-year-old woman with previous diagnosis of normal pressure hydrocephalus and who was brought to our hospital with altered mental status and urinary incontinence. Medical history of hypertension, hematological disorders or severe head trauma was absent. Platelet count and coagulation profile were unremarkable. An initial head computed tomography (CT showed sulcal enlargement and ventricular dilatation, but no evidence of ICH. A tap test indicated as a guide to case selection for shunt surgery accidentally resulted in cerebrospinal fluid (CSF overdrainage. The patient presented sudden neurological deterioration, with sluggishly responsive pupils and generalized tonic-clonic seizures. A new head CT demonstrated multiple supra and infratentorial ICH. The patient became comatose and had a fatal course. Hence, CSF overdrainage may either cause or precipitate multiple simultaneous ICHs, affecting both the infratentorial and supratentorial regions.

  17. An analysis of the cerebrospinal fluid dynamics in patients with normal pressure hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Mabe, Hideo; Nagai, Hajime (Nagoya City Univ. (Japan). Faculty of Medicine); Banno, Tatsuo

    1994-07-01

    Using a cine mode technique and a gradient-echo magnetic resonance (MR) sequencing, the MR signal intensity of the aqueduct has been evaluated in twelve patients suspected of normal pressure hydrocephalus (NPH). In patients with a substantial cerebrospinal fluid (CSF) circulation disturbance in the subarachnoid space, marked changes in the signal intensity of the aqueduct were seen during heart cycles, whereas in patients with less of a CSF circulation disturbance, changes in the signal intensity of the aqueduct were not as marked. Further, all patients manifesting marked changes in the signal intensity of the aqueduct showed a clinical improvement in their symptoms after undergoing a shunt. These results suggest that cine-mode MRI is useful for assessing the CSF dynamics and may be helpful in selecting patients who would benefit from shunt therapy. (author).

  18. Clinical value of HIV-1 matched detection in patients’ blood and cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    E. V. Stepanova

    2013-01-01

    Full Text Available A comparative investigation has been applied to 100 HIV infected patients with CD4 lymphocytes rate <350 cells/microliter, demanding HAART prescription, divided into two groups: 1 – without clinical features of CNS damage (54 people and 2 – with features of CNS damage of various etiology (46 people. HIV viral load (VL indices in blood plasma and cerebrospinal fluid (CSF have been examined. 45,7% of damages are caused with mixed infections. CSF HIV VL level with the 2 group patients is 7,6 times as high as that of 1 group patients. HIV VL in plasma is considerably higher than in CSF. Eight patients showed increased CSF HIV VL. Brain damages of various etiology with clinical implications violate hematoencephalic barrier integrity, contribute to HIV accumulation in CSF and intensify virus replication in brain tissue. It has been concluded that CSF examination for HIV is expedient.

  19. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature.

    Science.gov (United States)

    Grimes, D T; Boswell, C W; Morante, N F C; Henkelman, R M; Burdine, R D; Ciruna, B

    2016-06-10

    Idiopathic scoliosis (IS) affects 3% of children worldwide, yet the mechanisms underlying this spinal deformity remain unknown. Here we show that ptk7 mutant zebrafish, a faithful developmental model of IS, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yields IS phenotypes. We define a finite developmental window for motile cilia in zebrafish spine morphogenesis. Notably, restoration of cilia motility after the onset of scoliosis blocks spinal curve progression. Together, our results indicate a critical role for cilia-driven CSF flow in spine development, implicate irregularities in CSF flow as an underlying biological cause of IS, and suggest that noninvasive therapeutic intervention may prevent severe scoliosis.

  20. A collective review of syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis

    Directory of Open Access Journals (Sweden)

    Jian-hua WU

    2016-04-01

    Full Text Available The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL is characterized by recurrent attacks of paroxysmal headache, accompanying with neurological deficits and lymphocytic pleocytosis. Clinical features of the syndrome are nonspecific that it is bound to be confused with transient ischemic attack, intracranial tumor, viral encephalitis, migraine and other diseases. In fact, it is usually mis-diagnosed at the initial visits. So far, there is only one HaNDL case reported in China. Therefore the etiology, clinical features, diagnosis, and treatment are herewith reviewed to improve the knowledge regarding this syndrome. DOI: 10.11855/j.issn.0577-7402.2016.04.16

  1. Analysis of Glutamic Acid in Cerebrospinal Fluid by Capillary Electrophoresis with High Frequency Conductivity Detection

    Institute of Scientific and Technical Information of China (English)

    Hai Yun ZHAI; Jun Mei WANG; Xiao Li YAO; Xue Cai TAN; Pei Xiang CAI; Zuan Guang CHEN

    2005-01-01

    A rapid method to determine glutamic acid (Glu) in cerebrospinal fluid (CSF) by capillary electrophoresis with high frequency conductivity detection (contactless conductivity detection) was described. The CSF sample was pretreated with silver cation resin to remove high concentration of Cl- ions in CSF. The separation was achieved in the buffer solution of 10 mmol/L Tris and 8 mmol/L boric acid at the separation voltage of 20.0 kV. Glu showed linear response in the range of 5.0×10-6 to 6.0×10-3 mol/L, the limit of detection was 1.0×10-6 mol/L. The method was used for analysis Glu in CSF satisfactorily with a recovery of 97.8-98.8%.

  2. Senescent Changes in Cerebrospinal Fluid Circulatory Physiology and Their Role in the Pathogenesis of Normal-tension Glaucoma

    NARCIS (Netherlands)

    Wostyn, Peter; De Groot, Veva; Van Dam, Debby; Audenaert, Kurt; De Deyn, Peter Paul

    2013-01-01

    PURPOSE: To evaluate the evidence supporting a role for senescent changes in cerebrospinal fluid (CSF) circulatory physiology in the pathogenesis of normal-tension glaucoma (NTG). DESIGN: Literature review and personal perspective of the authors. METHODS: Analysis of selected articles in the peer-re

  3. Lack of value of routine analysis of cerebrospinal fluid for prediction and diagnosis of external drainage-related bacterial meningitis

    NARCIS (Netherlands)

    Schade, RP; Schinkel, J; Roelandse, FWC; Geskus, RB; Visser, L.G.; van Dijk, J.M.C.; Voormolen, JHC; van Pelt, H; Kuijper, EJ

    2006-01-01

    Object. Routine microbiological and chemical analysis of cerebrospinal fluid (CSF) is often performed to diagnose external drainage-related bacterial meningitis (ED-BM) at an early stage. A cohort study was performed to investigate the value of several commonly used CSF parameters For the prediction

  4. Lack of value of routine analysis of cerebrospinal fluid for prediction and diagnosis of external drainage-related bacterial meningitis.

    NARCIS (Netherlands)

    Schade, R.P.; Schinkel, J.; Roelandse, F.W.; Geskus, R.B.; Visser, L.G.; Dijk, M.C.R.F. van; Voormolen, J.H.; Pelt, H. van; Kuijper, E.J.

    2006-01-01

    OBJECT: Routine microbiological and chemical analysis of cerebrospinal fluid (CSF) is often performed to diagnose external drainage-related bacterial meningitis (ED-BM) at an early stage. A cohort study was performed to investigate the value of several commonly used CSF parameters for the prediction

  5. Blocking of leukocyte accumulation in the cerebrospinal fluid augments bacteremia and increases lethality in experimental pneumococcal meningitis

    DEFF Research Database (Denmark)

    Brandt, Christian T; Lundgren, Jens D; Frimodt-Møller, Niels;

    2005-01-01

    The role of leukocyte accumulation in the cerebrospinal fluid (CSF) in the evolution of the pathophysiological changes that occur in bacterial meningitis is unclear. Here, we investigate how leukocyte recruitment to the CSF, modulated by the leukocyte blocker fucoidin, affects the extent of brain...

  6. Liquid chromatography-tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid.

    NARCIS (Netherlands)

    Ham, M. van der; Koning, T.J. de; Lefeber, D.J.; Fleer, A.; Prinsen, B.H.; Sain-van der Velden, M.G. de

    2010-01-01

    BACKGROUND: Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was v

  7. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum of rabbits: validation of an animal model used to measure drug concentrations in cerebrospinal fluid.

    Science.gov (United States)

    Madu, A; Cioffe, C; Mian, U; Burroughs, M; Tuomanen, E; Mayers, M; Schwartz, E; Miller, M

    1994-09-01

    Complete concentration-time data describing the pharmacokinetics of fluconazole in the cerebrospinal fluid (CSF) following a single dose are not available for humans or animals. We studied the pharmacokinetics of fluconazole with an indwelling intracisternal needle as described by R.G. Dacey and M.A. Sande (Antimicrob. Agents Chemother. 6:437-441, 1974). To determine whether the presence of an intracisternal needle alters pharmacokinetics in the CSF, we validated this model with uninfected rabbits by measuring pharmacokinetic constants following direct intracisternal and intravenous administration of fluconazole. Following direct injection, there was no alteration of elimination rates in the CSF with increasing sample number or time. Following intravenous administration, the penetration and kinetic constants were the same in individual animals from which multiple CSF samples were obtained as in a composite subject constructed by pooling virgin samples from different animals. The presence of the intracisternal needle did not alter CSF chemistry or leukocyte counts, and erythrocyte contamination was < 0.001%. While drug concentrations were measured by a microbiological assay, we also compared the sensitivity and reproducibility of a high-performance liquid chromatography (HPLC) assay with those of the microbiological assay. Following a single intravenous dose, the maximum concentration of the drug in serum, the time to maximum concentration of the drug in serum, the terminal elimination half-life in the CSF, and the percent penetration by fluconazole were 6.12 micrograms/ml, 1 h, 9.0 h, and 84.3%, respectively. We conclude that the sampling of CSF via an indwelling needle does not alter fluconazole pharmacokinetics, cause inflammation, or alter chemical parameters; that the microbiological assay is at least equivalent in sensitivity and reproducibility to the HPLC assay; and that robust parameters describing the pharmacokinetics of fluconazole are possible with this

  8. Enantioselective analysis of proteinogenic amino acids in cerebrospinal fluid by capillary electrophoresis-mass spectrometry.

    Science.gov (United States)

    Prior, Amir; Sánchez-Hernández, Laura; Sastre-Toraño, Javier; Marina, Maria Luisa; de Jong, Gerhardus J; Somsen, Govert W

    2016-09-01

    d-Amino acids (AAs) are increasingly being recognized as essential molecules in biological systems. Enantioselective analysis of proteinogenic AAs in biological samples was accomplished by CE-MS employing β-CD as chiral selector and ESI via sheath-liquid (SL) interfacing. Prior to analysis, AAs were fully derivatized with FMOC, improving AA-enantiomer separation and ESI efficiency. In order to optimize the separation and MS detection of FMOC-AAs, the effects of type and concentration of CD in the BGE, the composition of the SL, and MS-interfacing parameters were evaluated. Using a BGE of 10 mM β-CD in 50 mM ammonium bicarbonate (pH 8) containing 15% v/v isopropanol, a SL of isopropanol-water-1 M ammonium bicarbonate (50:50:1, v/v/v) at a flow rate of 3 μL/min, and a nebulizer gas pressure of 2 psi, 15 proteinogenic AAs could be detected with enantioresolutions up to 3.5 and detection limits down to 0.9 μM (equivalent to less than 3 pg AA injected). The selectivity of the method was demonstrated by the analysis of spiked cerebrospinal fluid, allowing specific detection of d-AAs. Repeatability and linearity obtained for cerebrospinal fluid were similar to standard solutions, with peak area and migration-time RSDs (n = 5) below 16.2 and 1.6%, respectively, and a linear response (R(2) ≥ 0.977) in the 3-90 μM range. PMID:27465690

  9. Quantitative evaluation of changes in gait after extended cerebrospinal fluid drainage for normal pressure hydrocephalus.

    Science.gov (United States)

    Yang, Felix; Hickman, Thu-Trang; Tinl, Megan; Iracheta, Christine; Chen, Grace; Flynn, Patricia; Shuman, Matthew E; Johnson, Tatyana A; Rice, Rebecca R; Rice, Isaac M; Wiemann, Robert; Johnson, Mark D

    2016-06-01

    Idiopathic normal pressure hydrocephalus (iNPH) is characterized by gait instability, urinary incontinence and cognitive dysfunction. These symptoms can be relieved by cerebrospinal fluid (CSF) drainage, but the time course and nature of the improvements are poorly characterized. Attempts to prospectively identify iNPH patients responsive to CSF drainage by evaluating presenting gait quality or via extended lumbar cerebrospinal fluid drainage (eLCD) trials are common, but the reliability of such approaches is unclear. Here we combine eLCD trials with computerized quantitative gait measurements to predict shunt responsiveness in patients undergoing evaluation for possible iNPH. In this prospective cohort study, 50 patients presenting with enlarged cerebral ventricles and gait, urinary, and/or cognitive difficulties were evaluated for iNPH using a computerized gait analysis system during a 3day trial of eLCD. Gait speed, stride length, cadence, and the Timed Up and Go test were quantified before and during eLCD. Qualitative assessments of incontinence and cognition were obtained throughout the eLCD trial. Patients who improved after eLCD underwent ventriculoperitoneal shunt placement, and symptoms were reassessed serially over the next 3 to 15months. There was no significant difference in presenting gait characteristics between patients who improved after drainage and those who did not. Gait improvement was not observed until 2 or more days of continuous drainage in most cases. Symptoms improved after eLCD in 60% of patients, and all patients who improved after eLCD also improved after shunt placement. The degree of improvement after eLCD correlated closely with that observed after shunt placement.

  10. Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

    Science.gov (United States)

    Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

    2012-06-01

    Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

  11. Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions.

    Science.gov (United States)

    Ueno, Masaki; Chiba, Yoichi; Murakami, Ryuta; Matsumoto, Koichi; Kawauchi, Machi; Fujihara, Ryuji

    2016-04-01

    Blood-borne substances can invade into the extracellular spaces of the brain via endothelial cells in sites without the blood-brain barrier (BBB), and can travel through the interstitial fluid (ISF) of the brain parenchyma adjacent to non-BBB sites. It has been shown that cerebrospinal fluid (CSF) drains directly into the blood via the arachnoid villi and also into lymph nodes via the subarachnoid spaces of the brain, while ISF drains into the cervical lymph nodes through perivascular drainage pathways. In addition, the glymphatic pathway of fluids, characterized by para-arterial pathways, aquaporin4-dependent passage through astroglial cytoplasm, interstitial spaces, and paravenous routes, has been established. Meningeal lymphatic vessels along the superior sagittal sinus were very recently discovered. It is known that, in mice, blood-borne substances can be transferred to areas with intact BBB function, such as the medial regions of the hippocampus, presumably through leaky vessels in non-BBB sites. In the present paper, we review the clearance mechanisms of interstitial substances, such as amyloid-β peptides, as well as summarize models of BBB deterioration in response to different types of insults, including acute ischemia followed by reperfusion, hypertension, and chronic hypoperfusion. Lastly, we discuss the relationship between perivascular clearance and brain disorders. PMID:26920424

  12. Expression of microRNAs miR-21 and miR-181c in cerebrospinal fluid and serum in canine meningoencephalomyelitis of unknown origin.

    Science.gov (United States)

    Gaitero, L; Russell, S J; Monteith, G; LaMarre, J

    2016-10-01

    The potential of microRNAs (miRNAs) as biomarkers for canine meningoencephalomyelitis of unknown origin (MUO) was investigated by using quantitative real-time (qRT)-PCR to determine the expression of microRNA-21 (miR-21) and microRNA-181c (miR-181c) in the cerebrospinal fluid (CSF) of dogs. Dogs with MUO (n = 10) had higher levels of expression of miR-21 and miR-181c in the CSF than dogs with non-inflammatory neurological diseases (n = 8). There was a positive correlation between CSF cellularity and expression of miRNAs in the CSF, particularly for miR-21 in the MUO group. PMID:27687938

  13. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

    Science.gov (United States)

    Sellgren, CM; Kegel, ME; Bergen, SE; Ekman, CJ; Olsson, S; Larsson, M; Vawter, MP; Backlund, L; Sullivan, PF; Sklar, P; Smoller, JW; Magnusson, PKE; Hultman, CM; Walther-Jallow, L; Svensson, CI; Lichtenstein, P; Schalling, M; Engberg, G; Erhardt, S; Landén, M

    2016-01-01

    Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID:23459468

  14. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

    Science.gov (United States)

    Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C; Otto, Markus; Tumani, Hayrettin

    2015-01-01

    Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.

  15. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

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    Ahmed Abdelhak

    2015-07-01

    Full Text Available Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.

  16. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

    Science.gov (United States)

    Sellgren, C M; Kegel, M E; Bergen, S E; Ekman, C J; Olsson, S; Larsson, M; Vawter, M P; Backlund, L; Sullivan, P F; Sklar, P; Smoller, J W; Magnusson, P K E; Hultman, C M; Walther-Jallow, L; Svensson, C I; Lichtenstein, P; Schalling, M; Engberg, G; Erhardt, S; Landén, M

    2016-01-01

    Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID:26666201

  17. Comparison of acridine orange and Gram stains for detection of microorganisms in cerebrospinal fluid and other clinical specimens.

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    Lauer, B. A.; Reller, L B; Mirrett, S

    1981-01-01

    Acridine orange, a fluorochrome strain, is potentially superior to the Gram stain in the direct microscopic examination of clinical specimens because it gives striking differential staining between bacteria and background cells and debris. Its value in clinical laboratories was evaluated by testing 209 cerebrospinal fluids and 288 other body fluids, tissues, and exudates by both techniques. Smears were made in duplicate, fixed with methanol, stained, and examined without knowledge of the resu...

  18. 1H NMR Analysis of Cerebrospinal Fluid from Alzheimer’s Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH

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    Thomas Cruz

    2014-02-01

    Full Text Available Two publications from the same research group reporting on the detection of new possible biomarkers for the early diagnosis of Alzheimer’s disease (AD, based on the analysis of cerebrospinal fluid samples (CSF with 1H Nuclear Magnetic Resonance (NMR, are at the origin of the present study. The authors observed significant differences in 1H NMR spectra of CSF from AD patients and healthy controls and, thus, proposed some NMR signals (without attribution as possible biomarkers. However, this work was carried out in non-standardized pH conditions. Our study aims at warning about a possible misinterpretation that can arise from 1H NMR analyses of CSF samples if pH adjustment is not done before NMR analysis. Indeed, CSF pH increases rapidly after removal and is subject to changes over conservation time. We first identify the NMR signals described by the authors as biomarkers. We then focus on the chemical shift variations of their NMR signals as a function of pH in both standard solutions and CSF samples. Finally, a principal component analysis of 1H NMR data demonstrates that the same CSF samples recorded at pH 8.1 and 10.0 are statistically differentiated.

  19. Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis

    Science.gov (United States)

    Yoshimi, N; Futamura, T; Bergen, S E; Iwayama, Y; Ishima, T; Sellgren, C; Ekman, C J; Jakobsson, J; Pålsson, E; Kakumoto, K; Ohgi, Y; Yoshikawa, T; Landén, M; Hashimoto, K

    2016-01-01

    Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD. PMID:26782057

  20. Neonatal high pressure hydrocephalus is associated with elevation of pro-inflammatory cytokines IL-18 and IFNγ in cerebrospinal fluid

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    Schaller Carlo

    2008-12-01

    Full Text Available Abstract Background In human neonatal high pressure hydrocephalus (HPHC, diffuse white matter injury and gliosis predispose to poor neuro-developmental outcome. The underlying mechanism for diffuse white matter damage in neonatal HPHC is still unclear. Analogous to inflammatory white matter damage after neonatal hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be involved in neonatal HPHC. If so, early anti-inflammatory therapy could ameliorate white matter damage in HPHC, before irreversible apoptosis has occurred. In HPHC and control neonates, we therefore aimed to compare cerebrospinal fluid (CSF concentrations of IL18, IFNγ and sFasL (interleukin 18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively. Methods In neonatal HPHC (n = 30 and controls (n = 15, we compared CSF concentrations of IL18, IFNγ and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20, aqueduct stenosis (n = 4, and fetal intra-cerebral haemorrhage (n = 6. Neonatal control CSF was derived from otherwise healthy neonates (n = 15, who underwent lumbar puncture for exclusion of meningitis. Results In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNγ concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values. Conclusion Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNγ in the CSF, whereas CSF apoptosis biomarkers (sFasL were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting could be helpful to preserve cerebral white matter.

  1. Cerebrospinal fluid levels of amyloid precursor protein are associated with ventricular size in post-hemorrhagic hydrocephalus of prematurity.

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    Diego M Morales

    Full Text Available Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF amyloid precursor protein (APP, neural cell adhesion molecule-L1 (L1CAM, neural cell adhesion molecule-1 (NCAM-1, and other protein mediators of neurodevelopment.The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH.CSF levels of APP, L1CAM, NCAM-1, and total protein (TP were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC, volume of CSF removed, and ventricular size were examined using correlation and regression analyses.CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR (Pearson R = 0.76, p = 0.004, followed by NCAM-1 (R = 0.66, p = 0.02 and L1CAM (R = 0.57,p = 0.055. TP was not correlated with FOR (R = 0.02, p = 0.95.Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant.

  2. Characterization of cerebrospinal fluid (CSF) and plasma NPY levels in normal volunteers over a 24-h timeframe.

    Science.gov (United States)

    Baker, Dewleen G; Bertram, Tobias Moeller; Patel, Piyush M; Barkauskas, Donald A; Clopton, Paul; Patel, Sejal; Geracioti, Thomas D; Haji, Uzair; O'Connor, Daniel T; Nievergelt, Caroline M; Hauger, Richard L

    2013-10-01

    Neuropeptide Y (NPY) is abundant in mammals, where it contributes to diverse behavioral and physiological functions, centrally and peripherally, but little information is available in regard to NPY cerebrospinal fluid (CSF)/plasma concentration relationships and dynamics. Since plasma NPY levels are commonly used as proxy "biomarkers" for central NPY activity in stress and mental health research in humans this study aims to better characterize the CSF/plasma NPY relationships. Subjects were eleven healthy male volunteers, admitted to the clinical research center for placement of an indwelling CSF catheter, as well as venous catheter, for 24-h collection of CSF NPY (cNPY) and plasma NPY (pNPY) samples. As observed in prior studies, group mean (SE) cNPY concentrations [792.1 (7.80) pg/mL] were higher than pNPY concentrations [220.0 (3.63) pg/mL]. For the eleven normal volunteers who had sufficient common (hourly) pNPY and cNPY data points, analysis of pNPY/cNPY concentration ratios and lagged cross-correlation analysis was completed. Average pNPY/cNPY concentration ratios ranged from .20 to .40 across study subjects, with a mean of .29. pNPY/cNPY cross correlation analyses, computed at varying time lags, were non-significant. An attempt was made to analyze the circadian rhythmicity of NPY secretion, but circadian components were not detectable. Using 24-h data collection, we characterized CSF/plasma NPY relationships, including presentation of evidence of weak CSF and plasma correlations, an important consideration for study design of NPY in stress or mental health.

  3. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer’s Disease in Human Cerebrospinal Fluid

    Science.gov (United States)

    Lee, Anita Y. H.; Song, Qinghua; Liaw, Andy; Wiener, Matt; Paweletz, Cloud P.; Seeburger, Jeffrey L.; Li, Jenny; Meng, Fanyu; Deyanova, Ekaterina G.; Mazur, Matthew T.; Settlage, Robert E.; Zhao, Xuemei; Southwick, Katie; Du, Yi; Holder, Dan; Sachs, Jeffrey R.; Laterza, Omar F.; Dallob, Aimee; Chappell, Derek L.; Snyder, Karen; Modur, Vijay; King, Elizabeth; Joachim, Catharine; Bondarenko, Andrey Y.; Shearman, Mark; Soper, Keith A.; Smith, A. David; Potter, William Z.; Koblan, Ken S.; Sachs, Alan B.

    2015-01-01

    Disease modifying treatments for Alzheimer’s disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001) and SME-2 (p = 0.0004) for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR), in AD were 21% (p = 0.039) and 17% (p = 0.026) lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic. PMID:26270474

  4. The effect of chronic osmotic disturbance on the concentrations of cations in cerebrospinal fluid.

    Science.gov (United States)

    Bradbury, M W; Kleeman, C R

    1969-09-01

    1. Adult cats were rendered hypo- and hypernatraemic by peritoneal dialysis. These states were maintained for periods of 2-5 days.2. The concentrations in cerebrospinal fluid (c.s.f.) of the cations, potassium, calcium and magnesium all decreased in the hyponatraemic animals and increased in the hypernatraemic animals. These shifts in c.s.f. cation concentrations did not relate to plasma changes in the same cations, which were often in the opposite direction.3. The relations of the cation concentrations to c.s.f. sodium were not linear and, in the cases of calcium and magnesium, the relevant cation concentration related better to the square rather than the first power of the c.s.f. sodium concentration.4. Brain water changed much less in the hypo- and hypernatraemic animals than might be anticipated from the shifts in blood osmolarity, plasma sodium concentration and muscle water.5. Isotonicity of the fluids in brain with blood plasma and c.s.f. appeared to be largely maintained by loss or gain of sodium and chloride ions by this tissue.6. The c.s.f. results may be partly due to a constant influx of the cation in question being diluted with more formed c.s.f. in hyponatraemia and less c.s.f. in hypernatraemia, but the deviations from linearity in the plots of c.s.f. cation against c.s.f. sodium suggest the influence of other factors. PMID:5352043

  5. Quantification of the cerebrospinal fluid from a new whole body MRI sequence

    Science.gov (United States)

    Lebret, Alain; Petit, Eric; Durning, Bruno; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe

    2012-03-01

    Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinal fluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.

  6. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    Energy Technology Data Exchange (ETDEWEB)

    Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))

    1989-10-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-(14C)antipyrine and 2-(14C)deoxy-D-glucose method. The treatment induced moderate (15 days, base excess (BE) 16 mM) to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

  7. Soluble CD14 levels in the serum, synovial fluid, and cerebrospinal fluid of patients with various stages of Lyme disease.

    Science.gov (United States)

    Lin, B; Noring, R; Steere, A C; Klempner, M S; Hu, L T

    2000-03-01

    Levels of circulating soluble CD14 (sCD14) in patients with various stages of Lyme disease (LD) were examined. Patients with early or untreated late LD had significantly higher levels of sCD14 than did healthy controls (P=.0001 and .0007, respectively); levels returned to normal within 3 months after antibiotic therapy. Patients with persistent posttreatment symptoms of LD had sCD14 levels equivalent to those of healthy controls. Differences in the serum sCD14 levels in patients with various stages of LD are likely to be directly correlated with differences in bacterial burden, suggesting that posttreatment symptoms may not require continued presence of the organism. sCD14 levels in the cerebrospinal fluid (CSF) of patients with any stage of LD were no different from those of control subjects. Levels of synovial fluid sCD14 from patients with Borrelia burgdorferi in their joints were elevated, compared with levels in normal serum, and may play a role in the pathogenesis of arthritis.

  8. Association of Brucella Meningoencephalitis with Cerebrospinal Fluid Shunt in A Child: A Case Report

    Directory of Open Access Journals (Sweden)

    Babak ABDINIA

    2013-02-01

    Full Text Available How to Cite This Article: Abdinia B, Barzegar M, Maleki M, Behbod H, Oskoui Sh. Association of Brucella Meningoencephalitis with Cerebrospinal Fluid Shunt in a Child: a Case Report. Iran J Child Neurol. 2013 Winter:7(1:35-38. Brucellosis is an endemic zoonosis in Iran. It is a systemic infection that can involve any organs or systems of the body and have variable presentations. Ventriculoperitoneal (VP shunt infections due to brucellosis have been rarely reported in the literatures.This  is  the  history  of  a  four  years  old  boy  who  developed  Brucella meningoencephalitis at the age of 42 months, whilst he had a VP shunt in situ for hydrocephalus treatment. Also, he presented brucellosis as acute abdomen. This patient was treated with trimethoprim-sulfamethoxazole, gentamicin and rifampicin. The shunt was extracted and all clinical and laboratory test abnormalities subsided through this management.We propose that in a patient with Brucella meningoencephalitis, the cerebrospinal  fluid shunt  system  can  be  extracted  and  treatment  with appropriate combination of antibiotics could be successful. Moreover, it shows that brucellosis should be considered in the differential diagnosis for acute abdomen and ascites in endemic regions.References1. Hasanjani Roushan MR, Mohrez M, Samilnejad Gangi SM, Soleimani Amiri MJ, Hajiahmadi M. Epidemiological features and clinical manifestations in 469 adult patients with brucellosis in babol, Northern Iran. Epidemiol infect 2004;132(6:1109-142. Bouza E, García de la Torre M, Parras F, Guerrero A, Rodríguez-Créixems M, Gobernado J. Brucellar meningitis. Brucellar meningitis. Rev Infect Dis 1987; 9(4:810-22.3. Young EJ. Brucella species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennetts Õs Principles and Practice of Infectious Diseases. 5th ed. New York: Churchill Livingstone; 2000. p. 86-93.4. Feiz J, Sabbaghian H, Miralai M. Brucellosis due to Brucella

  9. Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Recent studies have found that insulin-like growth factors (IGFs) and insulin-like growth factor binding protein-3 (IGFBP-3) have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear.OBJECTIVE: To explore the changes of insulin-like growth factor-Ⅱ (IGF-Ⅱ ) and IGFBP-3 in cerebrospinal fluid (CSF) of children with tuberculous meningitis and the significance of the changes.DESIGN: A non-randomized concurrent controlled study.SETTING: Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College.PARTICIPANTS: Thirty children with tuberculous meningitis (14 males and 16 females) were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children (13 males and 17 females) with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children (13 males and 17 females) without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children.METHODS: ① The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid (3 mL). The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined

  10. Body height, estimated cerebrospinal fluid pressure and open-angle glaucoma. The Beijing Eye Study 2011.

    Directory of Open Access Journals (Sweden)

    Jost B Jonas

    Full Text Available PURPOSE: To examine potential associations between body height, cerebrospinal fluid pressure (CSFP, trans-lamina cribrosa pressure difference (TLCPD and prevalence of open-angle glaucoma (OAG in a population-based setting. METHODS: The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years (range:50-93 years. A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP measurements, CSFP was calculated as CSFP[mmHg] = 0.44 × Body Mass Index[kg/m(2] + 0.16 × Diastolic Blood Pressure[mmHg]-0.18 × Age[Years]-1.91. RESULTS: Data of IOP and CSFP were available for 3353 (96.7% subjects. Taller body height was associated with higher CSFP (P<0.001; standardized correlation coefficient beta:0.13; regression coefficient B:0.29; 95% confidence interval (CI:0.25,0.33 after adjusting for male gender, urban region of habitation, higher educational level, and pulse rate. If TLCPD instead of CSFP was added, taller body height was associated with lower TLCPD (P<0.001;beta:-0.10;B:-0.20;95%CI:-0.25,-0.15. Correspondingly, higher CSFP was associated with taller body height (P = 0.003;beta:0.02;B:0.01;95%CI:0.00,0.02, after adjusting for age, gender, body mass index, pulse, systolic blood pressure, and blood concentration of cholesterol. If IOP was added to the model, higher CSFP was associated with higher IOP (P<0.001;beta:0.02;B:0.02;95%CI:0.01,0.03. TLCPD was associated with lower body height (P = 0.003;beta:-0.04;B -0.02,95%CI:-0.04,-0.01 after adjusting for age, body mass index, systolic blood pressure, pulse, blood concentrations of triglycerides, axial length, central corneal thickness, corneal curvature radius, and anterior chamber depth. Adding the prevalence of OAG to the multivariate analysis revealed, that taller body height was associated with a lower OAG prevalence (P = 0.03;beta:-0.03;B:-1.20;95%CI:-2.28,-0.12 after adjusting for

  11. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus.

    Science.gov (United States)

    Ho, Roger C; Thiaghu, C; Ong, Huiyi; Lu, Yanxia; Ho, Cyrus S; Tam, Wilson W; Zhang, Melvyn W

    2016-02-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating presentations of SLE and comprises of psychiatric, central and peripheral neurological signs and symptoms. Previous studies suggest the possible associations between various autoantibodies (Abs) and NPSLE. The magnitudes of such association varied between studies. We performed a meta-analysis to pool data on serum and cerebrospinal fluid (CSF) levels and positivity of Abs in blood and cerebrospinal fluid in patients with NPSLE and SLE. A systematic literature search was conducted to identify studies that fulfilled inclusion criteria. A random-effects model was used to calculate overall combined odd ratio (OR) and mean levels with its corresponding 95% confidence interval to evaluate the relationship between individual Abs and NPSLE patients relative to SLE patients. Forty-one studies met the inclusion criteria and were used in this analysis. There was a significantly greater proportion of NPSLE patients who demonstrated positivity for serum anti-cardiolipin (aCL) Abs (OR=1.63, p=0.016), lupus anticoagulants (LA) Abs (OR=1.91 p=0.01), anti-phospholipid (APL) Abs (OR=2.08, p=0.001), anti-ribosomal P Abs (OR=2.29, pAbs (OR=9.50, pAbs (OR=36.84, p=0.001) as compared to SLE patients. Among the 19 neuropsychiatric syndromes, the positivity of these serum autoantibodies were found specifically significantly associated with the manifestations of mood disorder, psychosis, cerebrovascular disease, seizure disorders, acute confusional state, cognitive dysfunction, headache, movement disorder, demyelinating syndrome and polyneuropathy, with ORs ranging from 1.84 to 4.73. Meta-regression identified proportion of women as significant moderator for the heterogeneity of aCL (p=0.004) and anti-neuronal Abs (p=0.0007); mean age for the heterogeneity of aCL (p=0.042) and LA (p=0.020) Abs, mean duration of illness for the heterogeneity of aCL Abs (p=0.035), and mean SLEDAI scores for the heterogeneity

  12. Three-dimensional cerebrospinal fluid flow within the human ventricular system.

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    Howden, L; Giddings, D; Power, H; Aroussi, A; Vloeberghs, M; Garnett, M; Walker, D

    2008-04-01

    Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a "nesting" approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant. PMID:18297492

  13. Research into the Physiology of Cerebrospinal Fluid Reaches a New Horizon: Intimate Exchange between Cerebrospinal Fluid and Interstitial Fluid May Contribute to Maintenance of Homeostasis in the Central Nervous System.

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    Matsumae, Mitsunori; Sato, Osamu; Hirayama, Akihiro; Hayashi, Naokazu; Takizawa, Ken; Atsumi, Hideki; Sorimachi, Takatoshi

    2016-07-15

    Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016. PMID:27245177

  14. Genome-wide copy number analysis of cerebrospinal fluid tumor cells and their corresponding archival primary tumors.

    Science.gov (United States)

    Magbanua, Mark Jesus M; Roy, Ritu; Sosa, Eduardo V; Hauranieh, Louai; Kablanian, Andrea; Eisenbud, Lauren E; Ryazantsev, Artem; Au, Alfred; Scott, Janet H; Melisko, Michelle; Park, John W

    2014-12-01

    A debilitating complication of breast cancer is the metastatic spread of tumor cells to the leptomeninges or cerebrospinal fluid (CSF). Patients diagnosed with this aggressive clinical syndrome, known as leptomeningeal carcinomatosis, have very poor prognosis. Despite improvements in detecting cerebrospinal fluid tumor cells (CSFTCs), information regarding their molecular biology is extremely limited. In our recent work, we utilized a protocol previously used for circulating tumor cell isolation to purify tumor cells from the CSF. We then performed genomic characterization of CSFTCs as well as archival tumors from the same patient. Here, we describe the microarray data and quality controls associated with our study published in the Cancer Research journal in 2013 [1]. We also provide an R script containing code for quality control of microarray data and assessment of copy number calls. The microarray data has been deposited into Gene Expression Omnibus under accession # GSE46068.

  15. Case of acute meningitis with clear cerebrospinal fluid: value of computed tomography for the diagnosis of central nervous system tuberculosis

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    Cesari, V.

    1986-11-06

    The author reports a case of acute meningitis with clear cerebrospinal fluid in which extensive bacteriologic investigations were negative making the etiologic diagnosis exceedingly difficult. Initiation of empiric antituberculous therapy was rapidly followed by clinical and biological improvement, without complications, and by resolution of abnormal findings on computed tomography of the brain. On these grounds, meningitis secondary to a tuberculoma in the temporal lobe was diagnosed. The author points out that tuberculous meningitis is still a severe, potentially fatal condition; this, together with the fact that tubercle bacilli are often very scarce or absent, requires that tuberculous meningitis be routinely considered in every patient with clear cerebrospinal fluid meningitis whose condition deteriorates. Computed tomography of the brain is essential to ensure rapid diagnosis and prompt initiation of antituberculous therapy. Lastly, the author points out that nowadays herpes simplex virus encephalopathy should also be considered.

  16. Interleukin-5 and interleukin-10 are major cytokines in cerebrospinal fluid from patients with active neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Rodrigues Jr. V.

    2000-01-01

    Full Text Available Neurocysticercosis (NCC is a common neurological disorder especially in developing countries, caused by infection of the brain with encysted larvae of the tapeworm Taenia solium. Seizures are a common finding associated with this disease. The objective of the present study was to evaluate the correlation between the levels of various cytokines present in the cerebrospinal fluid (CSF of patients with NCC and the severity of the disease. The levels of the cytokines IL-1ß, TNF-alpha, IL-5, IL-10 and IFN-gamma were determined in the CSF of 22 patients with active NCC, 13 patients with inactive NCC and 15 control subjects. CSF from patients with active NCC presented significantly higher IL-5 levels compared to control subjects. IL-5 and IL-10 levels in CSF from NCC patients with inflammatory CSF were significantly higher than those detected in non-inflammatory CSF. These results show a predominant Th2 lymphocyte activation in human NCC and also indicate the possible use of cytokines in the CSF as a marker for the differential diagnosis between inactive disease and the active form of NCC.

  17. Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.

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    Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D

    1999-01-01

    We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis.

  18. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    International Nuclear Information System (INIS)

    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (VCSF) and the T2 of CSF (T2,CSF) was calculated. The correlation between VCSF / T2,CSF and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular VCSF increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T2 of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T2 of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. (orig.)

  19. High resolution protein electrophoresis of 100 paired canine cerebrospinal fluid and serum.

    Science.gov (United States)

    Behr, Sébastien; Trumel, Cathy; Cauzinille, Laurent; Palenché, Florence; Braun, Jean-Pierre

    2006-01-01

    This study was performed to investigate the diagnostic relevance of cerebrospinal fluid (CSF) high resolution electrophoresis. The laboratory technique was applied to 100 paired samples of canine CSF and serum, with paired samples tested during the same analytical run, as recommended in human medicine. Ninety four of the dogs had a neurological disease and 6 healthy dogs served as a control group. A strong linear correlation between CSF total protein concentration and the albumin quota (AQ) was found in the control group and in the inflammatory (infectious or noninfectious), neoplastic, and miscellaneous groups: AQ = 0.015 CSF total protein--0.102, r = 0.990. This correlation suggests that an increased CSF total protein concentration can be an indicator of blood brain barrier dysfunction. The highest median AQ value was found in the aseptic suppurative meningitis group, but no statistical differences were found between this and the other groups. The AQ, calculated with this technique, did not provide any additional information. Moreover, although unexpected, the electrophoretic profiles were not characteristic of any particular disease. In conclusion, this study did not confirm high resolution electrophoresis of paired CSF and serum samples to be a valuable ancillary diagnostic tool for canine neurological diseases. PMID:16734104

  20. Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF and plasma ? method-comparison evaluations

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    Sérgio Monteiro de Almeida

    2014-07-01

    Full Text Available Increased plasma lactate levels can indicate the presence of metabolic disorders in HIV infected individuals. Objective: To determine whether a portable analyzer is valid for measuring cerebrospinal fluid (CSF and plasma lactate levels in HIV infected individuals. Method: CSF and plasma were collected from 178 subjects. Samples tested by the Accutrend® portable analyzer were compared to those tested by a reference device (SYNCHRON LX® 20. Results: The portable analyzer had in plasma sensitivity of 0.95 and specificity 0.87. For CSF the specificity was 0.95; the sensitivity 0.33; the negative predictive value was 95% and the positive predictive value 33%. Conclusions: These findings support the validity of the portable analyzer in measuring lactate concentrations in CSF that fall within the normal range. The relatively poor positive predictive value indicates that a result above the reference range may represent a “false positive test”, and should be confirmed by the reference device before concluding abnormality.

  1. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Vis, J.B. de; Zwanenburg, J.J.; Kleij, L.A. van der; Spijkerman, J.M.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Biessels, G.J. [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Petersen, E.T. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Hvidovre Hospital, Danish Research Centre for Magnetic Resonance, Hvidovre (Denmark)

    2016-05-15

    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T{sub 2} of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T{sub 1}-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (V{sub CSF}) and the T{sub 2} of CSF (T{sub 2,CSF}) was calculated. The correlation between V{sub CSF} / T{sub 2,CSF} and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular V{sub CSF} increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T{sub 2} of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T{sub 2} of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. (orig.)

  2. [Assessment of a commonly available latex particle agglutination test in rapid, bacteriologic cerebrospinal fluid diagnosis].

    Science.gov (United States)

    Grubbauer, H M; Dornbusch, H J; Zobel, G; Thiel, W

    1988-01-01

    36 cerebrospinal fluid specimens (CSF) from patients with bacterial meningitis were tested for the presence of bacterial antigens with the "Slidex Meningite Kit" (Bio Merieux). This kit has latex particles coated with antibodies against hemophilus influenzae type B (Hib) streptococcus pneumoniae (SP) and neisseria meningitidis (NM) group A and C. With the LAT we could detect the bacterial antigens in 84% of bacterial meningitis cases, 23 of the 27 of Hib meningitis (85.2%), all of the 6 cases of SP meningitis (100%) and two of the three NM meningitis cases. The test is handicapped by the fact, that there is no antiserum against NM sero-group B, the main cause of NM meningitis in Austria. There were no false positive results with the LAT. False negative results were obtained in 19.2% of Hib and in one case of NM. Even under sufficient antibiotic therapy and with negative culture we could detect 9 Hib- and 1 NM-cases during the first 12-48 hours of therapy with this method. The LAT-Kit is a useful addition to standard methods of CSF examinations in bacterial meningitis. With the LAT a rapid bacteriological diagnosis is possible within 15 minutes. The Kit is also able to identify bacterial antigens even with negative culture and after initiation of antibiotic treatment. PMID:3133628

  3. Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial meningitis.

    Science.gov (United States)

    Paradowski, M; Lobos, M; Kuydowicz, J; Krakowiak, M; Kubasiewicz-Ujma, B

    1995-08-01

    We carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment. Convenience of serum sampling constitutes an advantage over traditional BM parameters in CSF. PMID:8521602

  4. Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome

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    Lestaevel, P.; Grison, S.; Favé, G.; Elie, C.; Dhieux, B.; Martin, J. C.; Tack, K.; Souidi, M.

    2016-01-01

    Natural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg·L−1 for male rats and 40 mg·L−1 for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L−1 NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L−1 NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function. PMID:27247806

  5. Myelin basic protein determination in cerebro-spinal fluid of children with tuberculous meningitis

    International Nuclear Information System (INIS)

    Myelin basic protein (MBP), an indicator of neural tissue damage in cerebro-spinal fluid, was studied in patients with tuberculous meningitis (TBM). MBP levels were elevated in 62% of the cases of TBM, the levels being 13.3+-18.8 ng/mL, compared with control levels of 1.34+-0.55 ng/mL(p<0.001). MBP level was related to certain clinical features of the disease, such as level of consciousness, neurological characteristics associated with signs of raised intracranial tension and the presence of arteritis associated with hydrocephalus. However, its greatest significance was its correlation with the progress of disease. Persistence of high levels of MBP over a period of a few weeks was associated with little or no improvement in the clinical state of the patient or a higher mortality rate. Return to normal levels of MBP indicated a more favourable outcome of disease. Hence MBP estimation gave not only an indicator of the degree of neurological damage but also an important marker to evaluate patients' progress and response to treatment. (author)

  6. Identification of Disease Markers in Human Cerebrospinal Fluid Using Lipidomic and Proteomic Methods

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    Alfred N. Fonteh

    2006-01-01

    Full Text Available Lipids comprise the bulk of the dry mass of the brain. In addition to providing structural integrity to membranes, insulation to cells and acting as a source of energy, lipids can be rapidly converted to mediators of inflammation or to signaling molecules that control molecular and cellular events in the brain. The advent of soft ionization procedures such as electrospray ionization (ESI and atmospheric pressure chemical ionization (APCI have made it possible for compositional studies of the diverse lipid structures that are present in brain. These include phospholipids, ceramides, sphingomyelin, cerebrosides, cholesterol and their oxidized derivatives. Lipid analyses have delineated metabolic defects in disease conditions including mental retardation, Parkinson's Disease (PD, schizophrenia, Alzheimer's Disease (AD, depression, brain development, and ischemic stroke. In this review, we examine the structure of the major lipid classes in the brain, describe methods used for their characterization, and evaluate their role in neurological diseases. The potential utility of characterizing lipid markers in the brain, with specific emphasis on disease mechanisms, will be discussed. Additionally, we describe several proteomic strategies for characterizing lipid-metabolizing proteins in human cerebrospinal fluid (CSF. These proteins may be potential therapeutic targets since they transport lipids required for neuronal growth or convert lipids into molecules that control brain physiology. Combining lipidomics and proteomics will enhance existing knowledge of disease pathology and increase the likelihood of discovering specific markers and biochemical mechanisms of brain diseases.

  7. Detection of heat stable mycobacterial antigen in cerebrospinal fluid by Dot-Immunobinding assay

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    Mathai A

    2003-01-01

    Full Text Available Background: Isolation of Mycobacterium tuberculosis in cerebrospinal fluid (CSF specimen in patients with tuberculous meningitis (TBM is infrequent and carries low sensitivity. Thus development of an alternative laboratory diagnostic test is essential for the early diagnosis and treatment of TBM. Objective: A simple, rapid Dot immunobinding assay (Dot-Iba, for the laboratory diagnosis of TBM is devised. This method minimizes the risk of handling infectious material in the laboratory. Method: The Dot-Iba was standardized with heat-inactivated M tuberculosis antigen (PPD. The heat-inactivated CSF from TBM and non-TBM patients was similarly assayed and it can detect antigen upto 1ng/ml in CSF. Result: A positive result was obtained in all the five culture positive patients with TBM and in 20/25 probable TBM. A negative result was obtained in 38/40 CSF from disease control group. The overall sensitivity and specificity of Dot-Iba was 83.3% and 95% respectively. Conclusion: Dot-Iba can be used as an adjunct for the laboratory diagnosis of TBM, particularly in culture negative TBM patients and also in those clinical situations where no laboratory tests are available to distinguish between TBM and partially treated pyogenic meningitis.

  8. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    Science.gov (United States)

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-γ concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-γ may be associated with EV71-induced neuropathology. PMID:25611005

  9. Selenium speciation in paired serum and cerebrospinal fluid samples of sheep.

    Science.gov (United States)

    Humann-Ziehank, Esther; Ganter, Martin; Michalke, Bernhard

    2016-01-01

    This study was performed to characterise selenium (Se) and Se species in cerebrospinal fluid (CSF) of sheep and its relation to the respective Se concentrations in serum. Paired samples from 10 adult sheep were used for the study. Five sheep were fed a diet with a marginal Se concentration of SePP), selenomethionine, glutathione peroxidase-bound Se (Se-GPx), selenocystine, thioredoxin reductase-bound Se, ovine serum albumin-bound Se (Se-OSA), SeIV and SeVI in ovine serum and CSF. Quantitatively, SePP is the main selenoprotein in ovine serum followed by Se-GPx. The CSF/blood ratio of albumin (QAlbumin) reflected a physiological function of the blood-CSF barrier in all sheep. QSe-species were higher than QAlbumin both feeding groups, supporting the hypothesis of local production of Se species in the brain. Significant positive regression lines for CSF vs. serum were found for albumin and Se-OSA only, suggesting a role of albumin to convey Se across the blood-CSF barrier. The ovine model, together with the IEC-ICP-DRC-MS technique to characterise the Se species, might be a worthwhile model for further studies as repeated sample collection as well as modification of the nutritional status is feasible and effective. PMID:26653738

  10. Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

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    Ehling Rainer

    2011-10-01

    Full Text Available Abstract Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF of acute and chronic central (CNS and peripheral nervous system (PNS diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS, acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM and PNS (Guillain-Barré syndrome; GBS, as well as in non-inflammatory neurological controls (OND in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.

  11. Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus

    Science.gov (United States)

    Hochhaus, Frederike; Koehne, Petra; Schäper, Christoph; Butenandt, Otfrid; Felderhoff-Mueser, Ursula; Ring-Mrozik, Elfride; Obladen, Michael; Bührer, Christoph

    2001-01-01

    Background Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. Methods NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. Results NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p 1 pg/mL) in 14/31 hydrocephalus samples at 2–51 pg/mL but in none of 11 control samples (p = 0.007). Conclusion NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP. PMID:11580868

  12. Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus

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    Felderhoff-Mueser Ursula

    2001-08-01

    Full Text Available Abstract Background Elevated intracranial pressure (ICP resulting from impaired drainage of cerebrospinal fluid (CSF causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF and neurotrophin-3 (NT-3 have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. Methods NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery. CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. Results NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p 1 pg/mL in 14/31 hydrocephalus samples at 2–51 pg/mL but in none of 11 control samples (p = 0.007. Conclusion NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP.

  13. Cerebrospinal fluid soluble L-selectin (sCD62L) in meningoencephalitis.

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    Bührer, C; Herold, R; Stibenz, D; Henze, G; Obladen, M

    1996-01-01

    The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis. PMID:8669926

  14. Increased cerebrospinal fluid concentrations of soluble Fas (CD95/Apo-1) in hydrocephalus

    Science.gov (United States)

    Felderhoff-Mueser, U; Herold, R; Hochhaus, F; Koehne, P; Ring-Mrozik, E; Obladen, M; Buhrer, C

    2001-01-01

    BACKGROUND AND AIMS—The ventricular enlargement observed in children with chronically raised intracranial pressure (ICP) causes a secondary loss of brain tissue. In animal studies of hydrocephalus, programmed cell death (apoptosis) has been found as a major mechanism of neuronal injury. One of the regulators of the apoptotic cell death programme is the receptor mediated Fas/Fas ligand interaction.
METHODS—The apoptosis regulating cytokines soluble Fas (sFas) and soluble Fas ligand (sFasL) were studied in the cerebrospinal fluid (CSF) of 31 hydrocephalic children undergoing shunt surgery for symptomatic hydrocephalus and 18controls.
RESULTS—High concentrations of sFas were observed in children with hydrocephalus (median 252 ng/ml); in controls sFas was below the detection limit (0.5 ng/ml). sFasL was undetectable in all but one sample.
CONCLUSION—High concentrations of sFas in the CSF of children with hydrocephalus suggest intrinsic sFas production, potentially antagonising pressure mediated Fas activation.

 PMID:11259245

  15. A Three years retrospective analysis of agents isolated from cerebrospinal fluid in a University Hospital

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    Barış Otlu

    2012-03-01

    Full Text Available Objectives: In this study, we aimed to investigate the agents which were isolated from cerebrospinal fluid (CSF samples in our hospital for three years, retrospectively.Materials and methods: The CSF samples, which were sent our laboratory, of the patients those had presumptive diagnosis of meningitis between September 2008 and September 2011 were included into the study. Isolated bacteria were identified with conventional methods, biochemical tests and/or Phonix (BD, US kits. Antimicrobial susceptibility of the strains were investigated according to Clinical Laboratory Standards Institute (CLSI recommendations.Results: 11 Streptococcus pneumoniae, 8 Klebsiella pneumoniae, 7 Pseudomonas aeruginosa, 7 Acinetobacter baumannii, 5 Escherichia coli, 4 Enterococcus spp., 2 Enterobacter spp., 25 Coagulase-negative staphylococcus, 1 Morganella morganii, 2 Neisseria meningitidis, 1 Brucella spp., and 1 Candida albicans were isolated (overall n:74; 5.2% from total 1408 CSF samples. In susceptibility test, 2 S.pneumonia was found as penicillin-resistant, and one E.coli and two K.pneumoniae were found as extended spectrum of beta-lactamase producers. Additionally, carbapenem resistance was detected in three A.baumannii and one P.aeruginosa strains.Conclusion: Determination of agent profile and antimicrobial resistance pattern from different localizations and patients’ groups will help to improve protective and therapeutic health policies.

  16. Age-specific characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid dynamics.

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    Marianne Schmid Daners

    Full Text Available The objective of this work is to quantify age-related differences in the characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid (CSF dynamics. To this end, 3T phase-contrast magnetic resonance imaging blood and CSF flow data of eleven young (24 ± 3 years and eleven elderly subjects (70 ± 5 years with a comparable sex-ratio were acquired. Flow waveforms and their frequency composition, transfer functions from blood to CSF flows and cross-correlations were analyzed. The magnitudes of the frequency components of CSF flow in the aqueduct differ significantly between the two age groups, as do the frequency components of the cervical spinal CSF and the arterial flows. The males' aqueductal CSF stroke volumes and average flow rates are significantly higher than those of the females. Transfer functions and cross-correlations between arterial blood and CSF flow reveal significant age-dependence of phase-shift between these, as do the waveforms of arterial blood, as well as cervical-spinal and aqueductal CSF flows. These findings accentuate the need for age- and sex-matched control groups for the evaluation of cerebral pathologies such as hydrocephalus.

  17. Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.

    Science.gov (United States)

    Habel, A H; Simpson, H

    1976-09-01

    The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive.

  18. Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis.

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    Bettina Kuenz

    Full Text Available BACKGROUND: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS. METHODOLOGY/PRINCIPAL FINDINGS: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS, relapsing-remitting (RR and chronic progressive (CP MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138- and plasma blasts (CD19+CD138+ in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP-9 and the B cell chemokine CxCL-13. CONCLUSIONS: Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS.

  19. ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

    International Nuclear Information System (INIS)

    The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma

  20. Segmentation of brain parenchyma and cerebrospinal fluid in multispectral magnetic resonance images.

    Science.gov (United States)

    Lundervold, A; Storvik, G

    1995-01-01

    Presents a new method to segment brain parenchyma and cerebrospinal fluid spaces automatically in routine axial spin echo multispectral MR images. The algorithm simultaneously incorporates information about anatomical boundaries (shape) and tissue signature (grey scale) using a priori knowledge. The head and brain are divided into four regions and seven different tissue types. Each tissue type c is modeled by a multivariate Gaussian distribution N(mu(c),Sigma(c)). Each region is associated with a finite mixture density corresponding to its constituent tissue types. Initial estimates of tissue parameters {mu(c),Sigma(c )}(c=1,...,7) are obtained from k-means clustering of a single slice used for training. The first algorithmic step uses the EM-algorithm for adjusting the initial tissue parameter estimates to the MR data of new patients. The second step uses a recently developed model of dynamic contours to detect three simply closed nonintersecting curves in the plane, constituting the arachnoid/dura mater boundary of the brain, the border between the subarachnoid space and brain parenchyma, and the inner border of the parenchyma toward the lateral ventricles. The model, which is formulated by energy functions in a Bayesian framework, incorporates a priori knowledge, smoothness constraints, and updated tissue type parameters. Satisfactory maximum a posteriori probability estimates of the closed contour curves defined by the model were found using simulated annealing. PMID:18215837

  1. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification.

    Science.gov (United States)

    Krasota, Alexandr; Loginovskih, Natalia; Ivanova, Olga; Lipskaya, Galina

    2016-01-06

    Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

  2. Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola.

    Science.gov (United States)

    Pelkonen, Tuula; Roine, Irmeli; Anjos, Elizabete; Kaijalainen, Svetlana; Roivainen, Merja; Peltola, Heikki; Pitkäranta, Anne

    2012-07-01

    Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis.

  3. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

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    Alexandr Krasota

    2016-01-01

    Full Text Available Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1% patients compared with 75 (47.2%, 53 (33.3% and 31 (19.5% achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14, E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71 in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

  4. Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development.

    Science.gov (United States)

    Alonso, M I; Martín, C; Carnicero, E; Bueno, D; Gato, A

    2011-07-01

    Embryonic-cerebrospinal fluid (E-CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E-CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E-CSF contains all-trans-retinol and retinol-binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic-rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E-CSF helps to control RA synthesis in the IsO by means of the RBP and all-trans-retinol it contains; (2) E-CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E-CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. PMID:21594951

  5. Subarachnuid cerebral hemorrhage treated with unequal volume of cerebrospinal fluid replacement

    Institute of Scientific and Technical Information of China (English)

    Chen Min; Zhejiang; Tongxiang; Shen jinsong; Lu jianhong; Xu Yusi; Cai Aiying; Qiu Jiannin

    2000-01-01

    Objective To asscss the effcct and safely of treatment with unequal volume replacement of cerebrospinal fluid(CSF) in cases of subarachnosd hemorrhage(SAH). Background 48 cases of SAH were seleeted which comply to the diagnostic standard set bh the 2nd National meeting of cerebro-vascular diseases and confirmed by CT and CSF examination. Randomly 24 cases were treated as above called treated cases and the other 24 cases as control. Method Treated Treated cases, after successful spinal puncture, 5to 10 ml of CSF were withdrawn. Normal saline were replaced but the volume were 2ml less than the amount withdraw. This is repeated until 6-10ml were withdrawn. The last injeetion of normal saline was aeeompanied with 5mg of dexamethasonum. Cases treated replacement were between 1 to 4times. Result After replacement intracranial pressure (ICP) were generally lowered and headache immediately lcssened or relieved. No further bleeding or herniation of brain occurred. Discussion At present the replaccment of CSF are generally of equal volame. This may cause recurrent bleeding or herniation of brain. After unequal volume replacement, great fluctuation of ICP bu comparison may be lowered. In treated cases duration of headache cerebral vasospasm(CVS), ocurance of hydrocephlus were generally less than the control cases(p<0.05). No intracranial infection in treated casea. Conelusion Unequal volume replacement of CSF in treatment of SAH is effeetive. It is safer than equal volume replacement

  6. Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier

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    Zlokovic, B.V.; Segal, M.B.; Davson, H.; Jankov, R.M.

    1988-05-01

    Unidirectional flux of /sup 125/I-labeled DSIP at the blood-tissue interface of the blood-cerebrospinal fluid (CSF) barrier was studied in the perfused in situ choroid plexuses of the lateral ventricles of the sheep. Arterio-venous loss of /sup 125/I-radioactivity suggested a low-to-moderate permeability of the choroid epithelium to the intact peptide from the blood side. A saturable mechanism with Michaelis-Menten type kinetics with high affinity and very low capacity (approximate values: Kt = 5.0 +/- 0.4 nM; Vmax = 272 +/- 10 fmol.min-1) was demonstrated at the blood-tissue interface of the choroid plexus. The clearance of DSIP from the ventricles during ventriculo-cisternal perfusion in the rabbit indicated no significant flux of the intact peptide out of the CSF. The results suggest that DSIP crosses the blood-CSF barrier, while the system lacks the specific mechanisms for removal from the CSF found with most, if not all, amino acids and several peptides.

  7. Cerebrospinal fluid flow in patients with dilated ventricles studied with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Parkkola, R.K.; Komu, M.E.S. [Department of Diagnostic Radiology, University Hospital of Turku (Finland); Kotilainen, E.M.; Valtonen, S.O. [Department of Neurosurgery, University Hospital of Turku (Finland); Thomsen, C. [Department of Radiology, National Danish University Hospital, Copenhagen (Denmark); Gideon, P. [Danish Magnetic Resonance Research Center, Hvidovre Hospital (Denmark)

    2000-09-01

    The purpose of this study was to measure the cerebrospinal fluid (CSF) velocity and flow in the aqueduct in patients with wide ventricles with or without signs of normal pressure hydrocephalus (NPH) before and after shunt surgery. We studied 18 patients with wide ventricles with MRI and measured the CSF velocity values in the aqueducts. Twelve patients with the clinical triad of NPH were examined. Six patients were studied only before shunt surgery and 6 patients were studied both before and after shunt surgery. Three patients with wide ventricles without clinical triad of NPH, and 3 patients with hydrocephalus following subarachnoid hemorrhage were also examined. Seven NPH patients with hyperdynamic CSF flow and three NPH patients with normal CSF velocity and flow values showed a positive clinical response to shunt surgery. Two of the three patients with hydrocephalus and hyperdynamic CSF flow values in the aqueduct secondary to subarachnoid bleeding responded to shunt surgery. One patient with same disease and low CSF velocity and flow values did not respond. No change was detected in the CSF flow values of the aqueduct when measurements before and after shunt surgery were compared. Ventriculoperitoneal shunting does not change the CSF dynamics in the aqueduct. (orig.)

  8. Sandwich wound closure reduces the risk of cerebrospinal fluid leaks in posterior fossa surgery

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    Verena Heymanns

    2016-07-01

    Full Text Available Posterior fossa surgery is demanding and hides a significant number of obstacles starting from the approach to the wound closure. The risk of cerebrospinal fluid (CSF leakage in posterior fossa surgery given in the literature is around 8%. The present study aims to introduce a sandwich closure of the dura in posterior fossa surgery, which reduces significantly the number of CSF leaks (3.8% in the patients treated in our department. Three hundred and ten patients treated in our hospital in the years 2009-2013 for posterior fossa pathologies were retrospectively evaluated. The dura closure method was as following: lyophilized dura put under the dura and sealed with fibrin glue and sutures, dura adapting stitches, TachoSil® (Takeda Pharma A/S, Roskilde, Denmark, Gelfoam® (Pfizer Inc., New York, NY, USA and polymethylmethacrylate (osteoclastic craniotomy. The incidence of postsurgical complications associated with the dural closure like CSF leakage, infections, bleeding is evaluated. Only 3.8% of patients developed CSF leakage and only 0.5% needed a second surgery for CSF leakage closure. Two percent had a cerebellar bleeding with no need for re-operation and 3% had a wound infection treated with antibiotics. The sandwich wound closure we are applying for posterior fossa surgery in our patients correlates with a significant reduction of CSF leaks compared to the literature.

  9. Detection of Antibodies to Brucella Cytoplasmic Proteins in the Cerebrospinal Fluid of Patients with Neurobrucellosis

    Science.gov (United States)

    Baldi, Pablo C.; Araj, George F.; Racaro, Graciela C.; Wallach, Jorge C.; Fossati, Carlos A.

    1999-01-01

    The diagnosis of human neurobrucellosis usually relies on the detection of antibodies to Brucella lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) by agglutination tests or enzyme-linked immunosorbent assay (ELISA). Here we describe the detection of immunoglobulin G (IgG) to cytoplasmic proteins (CP) of Brucella spp. by ELISA and Western blotting in seven CSF samples from five patients with neurobrucellosis. While IgG to CP (titers of 200 to 12,800) and IgG to LPS (800 to 6,400) were found in the CSF of these patients, these antibodies were not detected in CSF samples from two patients who had systemic brucellosis without neurological involvement. The latter, however, had serum IgG and IgM to both LPS and CP. No reactivity to these antigens was found in CSF samples from 14 and 20 patients suffering from nonbrucellar meningitis and noninfectious diseases, respectively. These findings suggest that, in addition to its usefulness in the serological diagnosis of human systemic brucellosis, the ELISA with CP antigen can be used for the specific diagnosis of human neurobrucellosis. PMID:10473531

  10. Cerebrospinal fluid cytomorphologic findings in 41 intracranial tumors: a retrospective review

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    Maria José Sá

    1995-06-01

    Full Text Available The main objective of this retrospective review of clinical and cerebrospinal fluid (CSF data from 41 patients with intracranial tumors diagnosed between 1975 and 1989, is to report the role that the finding of neoplastic cells in CSF plays, specially when cerebral CT-scanning and MRI were not currently done. Another objective is to study the CSF proteic abnormalities in cerebral tumors. CSF cell count, cytomorphologic pictures obtained after sedimentation and protein findings are described. Tumor cells were seen in 12 cases (29%: medulloblastomas - 6, meningeal carcinomatosis - 3, multiforme glioblastoma - 1, ependymoma -1, cerebral metastasis -1; in two cases it was an unexpected finding. We noticed that tumoral localization next to the ventricles favoured cell exfoliation. Although pleocytosis was rare and uncorrelated with the presence of neoplastic cells, pathological cytomorphologic pictures appeared in most of the cases including all "positive" ones. Our results stress that the appearance of neoplastic cells in CSF remains helpful specially when it is an unexpected finding.

  11. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

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    Veening Jan G

    2012-08-01

    Full Text Available Abstract There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of β-endorphin (β-END, especially those involving the cerebrospinal fluid (CSF, as a message transport system to reach distant brain areas. The major source of β-END are the pro-opio-melano-cortin (POMC neurons, located in the arcuate hypothalamic nucleus (ARH, bordering the 3rd ventricle. In addition, numerous varicose β-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of β-END, independence of peripheral versus central levels, central β-END migration over considerable distances, behavioral effects of β-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain.

  12. Higher level of NT-proCNP in cerebrospinal fluid of patients with meningitis.

    Science.gov (United States)

    Tomasiuk, Ryszard; Lipowski, Dariusz; Szlufik, Stanislaw; Peplinska, Krystyna; Mikaszewska-Sokolewicz, Malgorzata

    2016-02-12

    Aminoterminal pro-C type natriuretic peptide (NT-proCNP) as an active form of CNP, has been recently proven to be a potential marker of sepsis and to be linked to inflammatory diseases. So far, there are no studies describing the level of NT-proCNP in meningitis. The purpose of this study was to evaluate the diagnostic value of NT-proCNP in cerebrospinal fluid (CSF) in patients with meningitis and to compare it with the serum level of CRP and procalcitonin (PCT) in this group of patients. The results were compared to serum levels of CRP, PCT and CSF levels of cytosis, protein and lactate. NT-proCNP levels were statistically significant between the control group and the meningitis groups (p=0.02; R=0.3). We also noted a correlation between the level of NT-proCNP in the CSF of all of the study groups (controls and meningitis patients) and the CSF levels of cytosis (p0.05; R=0.11). These results suggest that NT-proCNP could be a potential marker of meningitis, but it cannot be used to distinguish between the types of meningitis.

  13. Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections.

    Science.gov (United States)

    Pashenkov, Mikhail; Teleshova, Natalia; Kouwenhoven, Mathilde; Smirnova, Tatiana; Jin, Ya Ping; Kostulas, Vasilios; Huang, Yu Min; Pinegin, Boris; Boiko, Alexey; Link, Hans

    2002-01-01

    Dendritic cells (DC) accumulate in the CNS during inflammation and may contribute to local immune responses. Two DC subsets present in human cerebrospinal fluid (CSF) are probably recruited from myeloid (CD11c(+)CD123(dim)) and plasmacytoid (CD11c(-)CD123(high)) blood DC. In bacterial meningitis and especially in Lyme meningoencephalitis, numbers of myeloid and plasmacytoid DC in CSF were increased, compared to non-inflammatory neurological diseases, and correlated with chemotactic activity of CSF for immature monocyte-derived DC (moDC). Multiple DC chemoattractants, including macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-1, MCP-3, RANTES and stromal cell-derived factor (SDF)-1alpha were elevated in CSF in these two neuroinfections. Chemotaxis of immature moDC induced by these CSFs could be partially inhibited by mAbs against CXCR4, the receptor for SDF-1alpha, and CD88, the receptor for C5a. SDF-1alpha present in CSF also chemoattracted mature moDC, which in vivo could correspond to a diminished migration of antigen-bearing DC from the CSF to secondary lymphoid organs. Regulation of DC trafficking to and from the CSF may represent a mechanism of controlling the CNS inflammation.

  14. [Ultrastructural location of enzymes in peripheral blood neutrophils and in cerebrospinal fluid neutrophils in neuroinfections].

    Science.gov (United States)

    Skotarczak, B

    1993-01-01

    Using cytochemical methods the location and activity were determined of alkaline phosphatase, ATP-ase and succinate dehydrogenase as representative enzymes for the metabolic processes in neutrophils isolated from blood and cerebrospinal fluid (CSF) of patients with meningococcal meningoencephalitis as compared with peripheral blood neutrophils in a control group. The study showed presence of phosphatase on the membranes of many intracellular structures. The activity of the enzymes was higher than in the control group in the membranes of neutrophils in blood and CSF. This is explained as an effect of action of the chemotactic factor on the cell membrane and activation of the cell to movements and phagocytosis. ATP-ase activity in peripheral blood neutrophils in controls was found in all membranous structures in the cell. However, in peripheral blood neutrophils and CSF neutrophils in the acute stage of the disease the active enzyme was noted, in the first place, in cell membranes and digesting vacuoles, which reflected probably the direction of metabolic processes for phagocytosis and destroying of bacteria. The activity of succinate dehydrogenase was found in mitochondrial membranes. Peripheral blood and CSF neutrophils showed a high activity of the enzyme. In the CSF cells in acute phase atypical sites of succinate dehydrogenase activity were noted, which was explained as a sign of cell destruction.

  15. Cerebral venous overdrainage: an under-recognized complication of cerebrospinal fluid diversion.

    Science.gov (United States)

    Barami, Kaveh

    2016-09-01

    Understanding the altered physiology following cerebrospinal fluid (CSF) diversion in the setting of adult hydrocephalus is important for optimizing patient care and avoiding complications. There is mounting evidence that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. An evolved mechanism acting at the cortical bridging veins, known as the "Starling resistor," prevents overdrainage of cranial venous blood with upright positioning. This protective mechanism can become nonfunctional after CSF diversion, which can result in posture-related cerebral venous overdrainage through the cranial venous outflow tracts, leading to pathological states. This review article summarizes the relevant anatomical and physiological bases of the relationship between the craniospinal venous and CSF compartments and surveys complications that may be explained by the cerebral venous overdrainage phenomenon. It is hoped that this article adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients. PMID:27581321

  16. Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis

    Science.gov (United States)

    Rossitti, Sandro

    2013-01-01

    Background: Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. Methods: The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. Results: The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. Conclusions: The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics. PMID:23607064

  17. Hepatic cerebrospinal fluid pseudocyst: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Hsieh C

    2006-01-01

    Full Text Available An abdominal pseudocyst is a rare, but important complication in patients with a ventriculo-peritoneal (VP shunt insertion. Several predisposing factors for this complication have been suggested, including infection, obstruction or dislodgement, but the pathophysiology is still unknown. However, the abdominal inflammatory process is accepted widely as a hypothesis for the formation of an abdominal pseudocyst. In this study, we report the case of a 21-year-old male that presented with a high-grade fever, poor appetite, shortness of breath and unconsciousness 1 week after receiving a VP shunt insertion for obstructive hydrocephalus. Ultrasonography and computed tomographic scans of the abdomen revealed a well-defined large hepatic cyst surrounding the peritoneal tube of the VP shunt. A hepatic cerebrospinal fluid (CSF cyst was diagnosed and Staphylococcus epidermis was cultured via CSF. After externalization of the VP shunt and adequate antibiotic treatment, the hepatic cyst was resolved. There was no recurrence observed in the regular follow up.

  18. Mechanism for measurement of flow rate of cerebrospinal fluid in hydrocephalus shunts.

    Science.gov (United States)

    Rajasekaran, Sathish; Kovar, Spencer; Qu, Peng; Inwald, David; Williams, Evan; Qu, Hongwei; Zakalik, Karol

    2014-01-01

    The measurement of the flow rate of cerebrospinal fluid (CSF) or existence of CSF flow inside the shunt tube after shunt implant have been reported as tedious process for both patients and doctors; this paper outlines a potential in vitro flow rate measurement method for CSF in the hydrocephalus shunt. The use of implantable titanium elements in the shunt has been proposed to allow for an accurate temperature measurement along the shunt for prediction of CSF flow rate. The CSF flow velocity can be deduced by decoupling the thermal transfer in the measured differential time at a pair of measurement spots of the titanium elements. Finite element analyses on the fluidic and thermal behaviors of the shunt system have been conducted. Preliminary bench-top measurements on a simulated system have been carried out. The measured flow rates, ranging from 0.5 mm/sec to 1.0 mm/sec, which is clinically practical, demonstrate good agreements with the simulation results.

  19. Trans-sphenoidal treatment of postsurgical cerebrospinal fluid fistula: CT-guided closure

    Energy Technology Data Exchange (ETDEWEB)

    Floris, R. [Rome-2 Univ., Rome (Italy). Dept. of Radiology]|[IRCCS Santa Lucia, Rome (Italy)]|[Via A. Caroncini 27, I-00197 Rome (Italy); Salvatore, C.; Simonetti, G. [Rome-2 Univ., Rome (Italy). Dept. of Radiology; Fraioli, B.; Pastore, F.S.; Vagnozzi, R. [Department of Neurosurgery, University of Rome ``Tor Vergata``, Rome (Italy)

    1998-10-01

    Cerebrospinal fluid (CSF) leakage after trans-sphenoidal surgery is a troublesome complication with a risk of meningitis and pneumocephalus. We suggest CT-guided intrasphenoidal injection of fibrin sealant through a 12-gauge needle as a simple alternative to surgical management of CSF fistulae. We treated eight patients, operated via the trans-sphenoidal route (five pituitary adenomas, three craniopharyngiomas), for a postoperative CSF leak by CT-guided intrasphenoidal injection of fibrin sealant alone in three cases and fibrin sealant and autologous blood in 5. CT was obtained 10 days after the procedure in all cases. In four patients, the CSF leak was closed successfully at the first attempt. The procedure was repeated on the four remaining patients because only a reduction in leakage was obtained at the first attempt. This procedure preserves olfaction and avoids the risk of frontal lobe damage. It could therefore represent the treatment of choice in many cases of anterior cranial fossa postsurgical CSF leaks. (orig.) (orig.) With 3 figs., 1 tab., 30 refs.

  20. Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.

    Science.gov (United States)

    Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D

    1999-01-01

    We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis. PMID:10604277

  1. PBPK model of methotrexate in cerebrospinal fluid ventricles using a combined microdialysis and MRI acquisition.

    Science.gov (United States)

    Brandhonneur, Nolwenn; Noury, Fanny; Bruyère, Arnaud; Saint-Jalmes, Hervé; Le Corre, Pascal

    2016-07-01

    The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model. MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data. The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results. The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases. PMID:27142258

  2. Procoagulant Phospholipids and Tissue Factor Activity in Cerebrospinal Fluid from Patients with Intracerebral Haemorrhage

    Directory of Open Access Journals (Sweden)

    Patrick Van Dreden

    2014-01-01

    Full Text Available Brain contains large amounts of tissue factor, the major initiator of the coagulation cascade. Neuronal apoptosis after intracerebral haemorrhage (ICH leads to the shedding of procoagulant phospholipids (PPLs. The aim of this study was to investigate the generation of PPL, tissue factor activity (TFa, and D-Dimer (D-Di in the cerebrospinal fluid (CSF at the acute phase of ICH in comparison with other brain diseases and to examine the relationship between these factors and the outcome of ICH. CSF was collected from 112 patients within 48 hours of hospital admission. Thirty-one patients with no neurological or biochemical abnormalities were used to establish reference range in the CSF (“controls”. Thirty had suffered an ICH, and 51 other neurological diagnoses [12: ventricular drainage following brain surgery, 13: viral meningitis, 15: bacterial meningitis, and 11 a neurodegenerative disease (NDD]. PPL was measured using a factor Xa-based coagulation assay and TFa by one home test. PPL, D-Di, and TFa were significantly higher (P<0.001 in the CSF of patients with ICH than in controls. TFa levels were significantly (P<0.05 higher in ICH than in patients with meningitides or NDD. Higher levels (P<0.05 of TFa were observed in patients with ICH who died than in survivors. TFa measurement in the CSF of patients with ICH could constitute a new prognostic marker.

  3. Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span.

    Science.gov (United States)

    Wang, Lucy Y; Murphy, Richard R; Hanscom, Brett; Li, Ge; Millard, Steven P; Petrie, Eric C; Galasko, Douglas R; Sikkema, Carl; Raskind, Murray A; Wilkinson, Charles W; Peskind, Elaine R

    2013-10-01

    Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21-100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p = 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p = 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p = 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment.

  4. Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to onset.

    Science.gov (United States)

    Kornum, Birgitte Rahbek; Pizza, Fabio; Knudsen, Stine; Plazzi, Giuseppe; Jennum, Poul; Mignot, Emmanuel

    2015-10-01

    Type 1 narcolepsy is caused by a loss of hypocretin (orexin) signaling in the brain. Genetic data suggests the disorder is caused by an autoimmune attack on hypocretin producing neurons in hypothalamus. This hypothesis has however not yet been confirmed by consistent findings of autoreactive antibodies or T-cells in patient samples. One explanation for these negative results may be that the autoimmune process is no longer active when patients present to the clinic. With increasing awareness in recent years, more and more patients have been diagnosed closer and closer to disease onset. In this study, we tested whether an active immune process in the brain could be detected in these patients, as reflected by increased cytokine levels in the cerebrospinal fluid (CSF). Using multiplex analysis, we measured the levels of 51 cytokines and chemokines in the CSF of 40 type 1 narcolepsy patients having varying disease duration. For comparison, we used samples from 9 healthy controls and 9 patients with other central hypersomnia. Cytokine levels did not differ significantly between controls and patients, even in 5 patients with disease onset less than a month prior to CSF sampling. PMID:25771509

  5. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome.

    Directory of Open Access Journals (Sweden)

    Steven E Schutzer

    Full Text Available BACKGROUND: Neurologic Post Treatment Lyme disease (nPTLS and Chronic Fatigue (CFS are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS. METHODS AND PRINCIPAL FINDINGS: Pooled cerebrospinal fluid (CSF samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS, coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01. CFS (n = 43 had 2,783 non-redundant proteins, nPTLS (n = 25 contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes. CONCLUSIONS: nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

  6. Possible role of the cavernous sinus veins in cerebrospinal fluid absorption

    Directory of Open Access Journals (Sweden)

    Koh Lena

    2007-04-01

    Full Text Available Abstract The purpose of this investigation was to enhance our understanding of cerebrospinal fluid (CSF absorption pathways. To achieve this, Microfil (a coloured silastic material was infused into the subarachnoid space (cisterna magna of sheep post mortem, and the relevant tissues examined macroscopically and microscopically. The Microfil was taken up by an extensive network of extracranial lymphatic vessels in the olfactory turbinates. In addition however, Microfil also passed consistently through the dura at the base of the brain. Microfil was noted in the spaces surrounding the venous network that comprises the cavernous sinus, in the adventitia of the internal carotid arteries and adjacent to the pituitary gland. Additionally, Microfil was observed within the endoneurial spaces of the trigeminal nerve and in lymphatic vessels emerging from the epineurium of the nerve. These results suggest several unconventional pathways by which CSF may be removed from the subarachnoid space. The movement of CSF to locations external to the cranium via these routes may lead to its absorption into veins and lymphatics outside of the skull. The physiological importance of these pathways requires further investigation.

  7. Prevalence of HHV-6 in cerebrospinal fluid of children younger than 2 years of age with febrile convulsion.

    OpenAIRE

    Setareh Mamishi; Laura Kamrani; Masoud Mohammadpour; Jila Yavarian

    2014-01-01

    Background and Objective Febrile convulsion is a common disorder in children. Viral infections such as human herpes virus 6 (HHV-6) which results in roseola infantum may contribute to developing seizure. The objective of this study was to determine the prevalence of HHV-6 by detecting DNA in cerebrospinal fluid (CSF) of children with febrile convulsion and without any rash of roseola infantum. Materials and Methods In this descriptive cross-sectional study, CSF of 100 children younger than 2 ...

  8. Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture

    Energy Technology Data Exchange (ETDEWEB)

    Bienfait, H.P. [Gelre Hospital, location Lukas, Apeldoorn, Department of Neurology, Albert Schweitzerlaan 31, PO Box 9014, 7300 DS Apeldoorn (Netherlands); Department of Neuro-Oncology, Daniel den Hoed Kliniek, Academisch Ziekenhuis Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands); Gijtenbeek, J.M.M. [Department of Neuro-Oncology, Daniel den Hoed Kliniek, Academisch Ziekenhuis Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands); Department of Neurology, University Medical Center Nijmegen, St Radboud, Postlaan 4, 6525 GC Nijmegen (Netherlands); Bent, M.J. van [Department of Neuro-Oncology, Daniel den Hoed Kliniek, Academisch Ziekenhuis Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands); Bruin, H.G. de [Department of Radiology, Daniel den Hoed Kliniek, Academisch Ziekenhuis Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands); Voogt, P.J. [Department of Hematology, Daniel den Hoed Kliniek, Academisch Ziekenhuis Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands); Pillay, M. [Department of Nuclear Medicine, Daniel den Hoed Kliniek, Academisch Ziekenhuis Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands)

    2002-11-01

    We report a patient treated for small lymphocytic lymphoma/leukemia with cerebral venous and sinus thrombosis (CVST) after lumbar puncture with intrathecal administration of methotrexate (MTX). He also developed a cerebrospinal fluid flow block. This is the first report of an association between lumbar puncture and intrathecally administered MTX and the development of CVST. Intrathecal treatment in this patient was discontinued and he was successfully treated with high-dose low-molecular-weight heparin subcutaneously. (orig.)

  9. High-abundant protein depletion strategies applied on dog cerebrospinal fluid and evaluated by high-resolution mass spectrometry

    OpenAIRE

    Sundberg, Mårten; Bergquist, Jonas; Ramström, Margareta

    2015-01-01

    As the number of fully sequenced animal genomes and the performance of advanced mass spectrometry-based proteomics techniques are continuously improving, there is now a great opportunity to increase the knowledge of various animal proteomes. This research area is further stimulated by a growing interest from veterinary medicine and the pharmaceutical industry. Cerebrospinal fluid (CSF) is a good source for better understanding of diseases related to the central nervous system, both in humans ...

  10. Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

    OpenAIRE

    McLean, Samuel A.; Williams, David A.; Stein, Phyllis K.; Harris, Richard E.; Lyden, Angela K; Whalen, Gail; Park, Karen M; Liberzon, Israel; Sen, Ananda; Gracely, Richard H.; Baraniuk, James N.; Clauw, Daniel J

    2006-01-01

    Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, ...

  11. Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis

    OpenAIRE

    Kułakowska, Alina; Byfield, Fitzroy J; Żendzian-Piotrowska, Małgorzata; Zajkowska, Joanna M; Drozdowski, Wiesław; Mroczko, Barbara; Janmey, Paul A.; Bucki, Robert

    2014-01-01

    Background Tick-borne encephalitis (TBE) is a serious acute central nervous system infection that can result in death or long-term neurological dysfunctions. We hypothesize that changes in sphingosine-1-phosphate (S1P) concentration occur during TBE development. Methods S1P and interleukin-6 (IL-6) concentrations in blood plasma and cerebrospinal fluid (CSF) were measured using HPLC and ELISA, respectively. The effects of S1P on cytoskeletal structure and IL-6 production were assessed using r...

  12. Cerebrospinal fluid analysis in infectious diseases of the nervous system: when to ask, what to ask, what to expect

    Directory of Open Access Journals (Sweden)

    Luis dos Ramos Machado

    2013-09-01

    Full Text Available Cerebrospinal fluid (CSF analysis very frequently makes the difference to the diagnosis, not only in relation to infections but also in other diseases of the nervous system such as inflammatory, demyelinating, neoplastic and degenerative diseases. The authors review some practical and important features of CSF analysis in infectious diseases of the nervous system, with regard to acute bacterial meningitis, herpetic meningoencephalitis, neurotuberculosis, neurocryptococcosis, neurocysticercosis and neurosyphilis.

  13. Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis mimicking dengue encephalitis in a child

    OpenAIRE

    Indrajit Suresh; Priyanka Deb; Chandra Babu D.; Jeevan H.R.

    2015-01-01

    The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) has been infrequently reported in children. This condition can mimic many serious conditions of the central nervous system, while actually being benign in nature. The authors present the report of an 8 year old developmentally normal female with family and personal history of migraine, which was initially suspected to have Dengue encephalitis. She had an episode of seizures, meningism a...

  14. Meningeal Inflammation Increases Artemether Concentrations in Cerebrospinal Fluid in Papua New Guinean Children Treated with Intramuscular Artemether ▿

    OpenAIRE

    Manning, Laurens; Laman, Moses; Page-Sharp, Madhu; Salman, Sam; Hwaiwhanje, Ilomo; Morep, Namar; Siba, Peter; Mueller, Ivo; Karunajeewa, Harin A.; Davis, Timothy M. E.

    2011-01-01

    Although the artemisinin-associated neurotoxicity identified in vitro and in animal studies has not been confirmed clinically, only one adult study has measured cerebrospinal fluid (CSF) concentrations after administration of conventional doses. Potential artemisinin neurotoxicity could be serious in children, especially those with meningitis and, consequently, a compromised blood-brain barrier. We measured CSF/plasma artemether and dihydroartemisinin (DHA) concentrations in 32 Papua New Guin...

  15. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H;

    2015-01-01

    using an enzyme-linked immunosorbent assay. RESULTS: Soluble CD163 levels were significantly higher in the cerebrospinal fluid and serum of the participants with Type 2 diabetes compared with the control participants [cerebrospinal fluid: median (range) 107 (70-190) vs 84 (54-115) μg/l, P ....01 and serum: 2305 (920-7060) vs 1420 (780-2740) μg/l, P higher levels of soluble CD163 in the cerebrospinal fluid...... nerve function. Higher levels of soluble CD163 in people with diabetic polyneuropathy suggest that inflammation plays a role in the development of neural impairment. The relationship between cerebrospinal fluid soluble CD163 level and peripheral nerve conduction indicates that soluble CD163 may...

  16. Electroanalytical and surface plasmon resonance sensors for detection of breast cancer and Alzheimer's disease biomarkers in cells and body fluids.

    Science.gov (United States)

    Yang, Minghui; Yi, Xinyao; Wang, Jianxiu; Zhou, Feimeng

    2014-04-21

    Cancer and neurological disorders are two leading causes of human death. Their early diagnoses will either greatly improve the survival rate or facilitate effective treatments or modalities. Detection of biomarkers in body fluids and some tissues (e.g., blood, urine and cerebrospinal fluids) is relatively non-invasive and provides useful chemical and biological information that is complementary to tomographic imaging (e.g., magnetic resonance imaging, positron emission tomography and X-ray computed tomography). Recent years have witnessed the contributions from and potential applications of bioanalytical methods for early detection of major diseases. In this review, we survey some recent developments of electroanalytical (as a representative label-based technique) and surface plasmon resonance (SPR) (as a representative label-free technique) biosensors for detection of biomarkers relevant to etiologies of breast cancer and Alzheimer's disease (AD). While breast cancer is representative of cancers of complexity (multiple biomarkers, false positives from tomographic scans, and a need for more effective early diagnostic methods), AD is the most prevalent neurological disorder that is also linked to multiple biomarkers. Both electroanalytical and SPR-based sensors have attractive features of sensitivity, portability, obviation of large sample volumes, and capability of multiplexed detection. Various sensing protocols developed in the past five years are reviewed, demonstrating the feasibility of both techniques for diagnostic purposes. Problems inherent in these two techniques that must be overcome before being clinically viable are also discussed.

  17. Analgesic and thermic effects, and cerebrospinal fluid and plasma pharmacokinetics, of intracerebroventricularly administered morphine in normal and sensitized rats.

    Science.gov (United States)

    Bhargava, H N; Villar, V M; Cortijo, J; Morcillo, E J

    1998-02-01

    The relationship between asthma and opioids has barely been investigated. This study examines whether active sensitization of rats changes the analgesic and thermic effects of intracerebroventricular morphine or the pharmacokinetics of the drug. Morphine (5, 10 and 20 microg) was given intracerebroventricularly to sensitized (active immunization to ovalbumin and Al(OH)3 then airway challenge with ovalbumin after 12 days) and normal (i.e. non-sensitized) male Sprague-Dawley rats. The tail-flick latencies and changes in colon temperature were determined before morphine injection and at 30 min intervals for a period of 300 min afterwards. Results were expressed as the area under the time-response curve. The analgesic and hyperthermic response to morphine for sensitized rats was less than that obtained for normal rats. Cerebrospinal fluid and blood samples were collected periodically for a period of 240 min and morphine levels were determined by a highly sensitive radioimmunoassay. The pharmacokinetic parameters half-life, terminal elimination rate constant and the mean residence time were determined in both cerebrospinal fluid and plasma by non-compartmental analysis. The area under the cerebrospinal fluid concentration-time curve from time zero to infinity was higher for sensitized rats than for normal rats for all three doses of morphine but these differences did not correspond with similar changes in pharmacological responses. In conclusion, the attenuated analgesic and thermic responses to intracerebroventricular morphine in the sensitized rats might be a result of pharmacodynamic alterations rather than to pharmacokinetic changes. PMID:9530988

  18. The diagnosis of metachromatic leucodystrophy during life: metachromatic lipids in saliva and cerebrospinal fluid sediments and in the parotid glands

    Directory of Open Access Journals (Sweden)

    Horacio M. Canelas

    1964-06-01

    Full Text Available The authors report the study of saliva sediment in 4 cases of juvenile metachromatic leucodystrophy belonging to the same family (and else in a sister of one of these cases presenting the characteristic neurological picture but with no metachromasia demonstrable by the Austin test in urine or by biopsies, in 6 normal relatives of the patients with Scholz disease, in 9 cases of various diseases of the nervous system, and in 10 normal subjects. The presence of metachromatic bodies staining in a pinkish red colour with acid blue toluidine dye was demonstrated in the saliva sediment of the 4 cases of metachromatic leucodystrophy. In 2 of these patients biopsies of the parotid gland, stained with cresyl violet dye, showed the presence of intracellular brownish metachromatic bodies. In these 2 cases the study of cerebrospinal fluid sediment also disclosed the presence of metachromatic bodies. Furthermore, a chromatographic qualitative test for metachromatic lipids yielded positive results in saliva, cerebrospinal fluid, and urine sediments. The conclusion was drawn that the search for metachromatic bodies in cerebrospinal fluid and mainly in saliva sediment may be of help in disclosing or ratifying the diagnosis of metachromatic leucodystrophy during life.

  19. Evaluation of high sensitivity C-reactive protein assay in cerebrospinal fluid on the Dimension RxL analyzer

    Directory of Open Access Journals (Sweden)

    Jozo Ćorić

    2012-04-01

    Full Text Available Introduction: Low sensitivity and specificity in traditional laboratory tests became insufficient for accurate diagnostics and initiation of proper treatment of patients infected with bacterial meningitis. High sensitivity C reactive protein (hsCRP may be an appropriate supplement for rapid diagnosis of bacterial meningitis. The subject of our investigation was the determination of C- reactive protein in cerebrospinal fluid (CSF duringacute bacterial meningitis.Methods: HsCRP was analysed by a sensitive immunoturbidimetric assay using the Dimension RxL analyser (Siemens. Cerebrospinal fluid concentrations of C-reactive protein have been measured in 20 patients(age range,1 to 50 years presenting with acute bacterial meningitis and also in a non-infected, non-inflamed control group (n=25.Results: The accuracy and precision of the method proved to be satisfactory. Repeatability of serial sampling for hsCRP described by coefficient of variation were CV=2.1-4.5%. This assay hsCRP in cerebrospinal fluid demonstrates adequate performance characteristics for routine clinical use. Elevated levels of CRP were found in 95% patients with bacterial meningitis. The mean CRP value in 25 uninfected control group was 0.25 mg/L (range 0.10-0.55. The mean CRP for patients with bacterial meningitis was 21.4 mg/L (range 0.40-100.Conclusions: A sensitive assay for CRP in CSF would be an useful adjunct to conventional investigation of acute infective meningitis.

  20. Allogeneic cartilage used for skull base plasty in children with primary intranasal encephalomeningocele associated with cerebrospinal fluid rhinorrhea.

    Science.gov (United States)

    Parízek, J; Mĕrićka, P; Nĕmecek, S; Nĕmecková, J; Zemánková, M; Sercl, M; Häringová, M

    1996-03-01

    Three children with primary intranasal encephalomeningocele associated with cerebrospinal fluid rhinorrhea were operated on at the Department of Neurosurgery, Hradec Králové. In two children, aged 4 and 9.5 years, freeze-dried allogeneic costal cartilage was glued into the skull base defect. This plugging was covered up with deep frozen allogeneic fascia lata. In the third child, an only 1-year-old boy, after transection of the neck of the encephalomeningocele freeze-dried allogeneic dura mater was glued on extradurally and deep-frozen allogeneic fascia lata applied intradurally. The cerebrospinal fluid rhinorrhea ceased immediately after surgery. Spontaneous atrophy of the intranasal portion of the encephalomeningocele was demonstrated respectively 11, 1, and 7 years postoperatively on computed tomography. To evaluate cartilage healing histologically, the extracted allogeneic cartilage used for orbital roof plasty after 4 months was examined. The extent of spotty regressions represented about 7% of the tissue volume. It is stressed that, once diagnosed, intranasal encephalomeningocele associated with cerebrospinal fluid rhinorrhea should be operated on for prevention of meningitis as soon as possible. PMID:8697455

  1. A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

    Science.gov (United States)

    Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

    2015-11-01

    In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. PMID:26247808

  2. Osmolality of Cerebrospinal Fluid from Patients with Idiopathic Intracranial Hypertension (IIH.

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    Elisabeth A Wibroe

    Full Text Available Idiopathic intracranial hypertension (IIH is a disorder of increased intracranial fluid pressure (ICP of unknown etiology. This study aims to investigate osmolality of cerebrospinal fluid (CSF from patients with IIH.We prospectively collected CSF from individuals referred on suspicion of IIH from 2011-2013. Subjects included as patients fulfilled Friedman and Jacobson's diagnostic criteria for IIH. Individuals in whom intracranial hypertension was refuted were included as controls. Lumbar puncture with ICP measurement was performed at inclusion and repeated for patients after three months of treatment. Osmolality was measured with a Vapor Pressure Osmometer.We collected 90 CSF samples from 38 newly diagnosed patients and 28 controls. At baseline 27 IIH-samples and at 3 months follow-up 35 IIH-samples were collected from patients. We found no significant differences in osmolality between 1 patients at baseline and controls (p = 0. 86, 2 patients at baseline and after 3 months treatment (p = 0.97, and 3 patients with normalized pressure after 3 months and their baseline values (p = 0.79. Osmolality in individuals with normal ICP from 6-25 cmH2O (n = 41 did not differ significantly from patients with moderately elevated ICP from 26-45 cmH2O (n = 21 (p = 0.86 and patients with high ICP from 46-70 cmH2O (n = 4 (p = 0.32, respectively. There was no correlation between osmolality and ICP, BMI, age and body height, respectively. Mean CSF osmolality was 270 mmol/kg (± 1 SE, 95% confidence interval 267-272 for both patients and controls.CSF osmolality was normal in patients with IIH, and there was no relation to treatment, ICP, BMI, age and body height. Mean CSF osmolality was 270 mmol/kg and constitutes a reference for future studies. Changes in CSF osmolality are not responsible for development of IIH. Other underlying pathophysiological mechanisms must be searched.

  3. Prion-seeding activity in cerebrospinal fluid of deer with chronic wasting disease.

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    Nicholas J Haley

    Full Text Available Transmissible spongiform encephalopathies (TSEs, or prion diseases, are a uniformly fatal family of neurodegenerative diseases in mammals that includes chronic wasting disease (CWD of cervids. The early and ante-mortem identification of TSE-infected individuals using conventional western blotting or immunohistochemistry (IHC has proven difficult, as the levels of infectious prions in readily obtainable samples, including blood and bodily fluids, are typically beyond the limits of detection. The development of amplification-based seeding assays has been instrumental in the detection of low levels of infectious prions in clinical samples. In the present study, we evaluated the cerebrospinal fluid (CSF of CWD-exposed (n=44 and naïve (n=4 deer (n=48 total for CWD prions (PrP(d using two amplification assays: serial protein misfolding cyclic amplification with polytetrafluoroethylene beads (sPMCAb and real-time quaking induced conversion (RT-QuIC employing a truncated Syrian hamster recombinant protein substrate. Samples were evaluated blindly in parallel with appropriate positive and negative controls. Results from amplification assays were compared to one another and to obex immunohistochemistry, and were correlated to available clinical histories including CWD inoculum source (e.g. saliva, blood, genotype, survival period, and duration of clinical signs. We found that both sPMCAb and RT-QuIC were capable of amplifying CWD prions from cervid CSF, and results correlated well with one another. Prion seeding activity in either assay was observed in approximately 50% of deer with PrP(d detected by IHC in the obex region of the brain. Important predictors of amplification included duration of clinical signs and time of first tonsil biopsy positive results, and ultimately the levels of PrP(d identified in the obex by IHC. Based on our findings, we expect that both sPMCAb and RT-QuIC may prove to be useful detection assays for the detection of prions in

  4. Utility of cerebrospinal fluid drug concentration as a surrogate for unbound brain concentration in nonhuman primates.

    Science.gov (United States)

    Nagaya, Yoko; Nozaki, Yoshitane; Kobayashi, Kazumasa; Takenaka, Osamu; Nakatani, Yosuke; Kusano, Kazutomi; Yoshimura, Tsutomu; Kusuhara, Hiroyuki

    2014-01-01

    In central nervous system drug discovery, cerebrospinal fluid (CSF) drug concentration (C(CSF)) has been widely used as a surrogate for unbound brain concentrations (C(u,brain)). However, previous rodent studies demonstrated that when drugs undergo active efflux by transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier, the C(CSF) overestimates the corresponding C(u,brain). To investigate the utility of C(CSF) as a surrogate for interstitial fluid (ISF) concentration (C(ISF)) in nonhuman primates, this study simultaneously determined the C(CSF) and C(ISF) of 12 compounds, including P-gp substrates, under steady-state conditions in cynomolgus monkeys using intracerebral microdialysis coupled with cisternal CSF sampling. Unbound plasma concentrations of non- or weak P-gp substrates were within 2.2-fold of the C(ISF) or C(CSF), whereas typical P-gp substrates (risperidone, verapamil, desloratadine, and quinidine) showed ISF-to-plasma unbound (K(p,uu,ISF)) and CSF-to-plasma unbound concentration ratios (K(p,uu,CSF)) that were appreciably lower than unity. Although the K(p,uu,CSF) of quinidine, verapamil, and desloratadine showed a trend of overestimating the K(p,uu,ISF), K(p,uu,CSF) showed a good agreement with K(p,uu,ISF) within 3-fold variations for all compounds examined. C(u,brain) of some basic compounds, as determined using brain homogenates, overestimated the C(ISF) and C(CSF). Therefore, C(CSF) could be used as a surrogate for C(ISF) in nonhuman primates.

  5. Cerebrospinal fluid flow impedance is elevated in Type I Chiari malformation.

    Science.gov (United States)

    Shaffer, Nicholas; Martin, Bryn A; Rocque, Brandon; Madura, Casey; Wieben, Oliver; Iskandar, Bermans J; Dombrowski, Stephen; Luciano, Mark; Oshinski, John N; Loth, Francis

    2014-02-01

    Diagnosis of Type I Chiari malformation (CMI) is difficult because the most commonly used diagnostic criterion, cerebellar tonsillar herniation (CTH) greater than 3-5 mm past the foramen magnum, has been found to have little correlation with patient symptom severity. Thus, there is a need to identify new objective measurement(s) to help quantify CMI severity. This study investigated longitudinal impedance (LI) as a parameter to assess CMI in terms of impedance to cerebrospinal fluid motion near the craniovertebral junction. LI was assessed in CMI patients (N = 15) and age-matched healthy controls (N = 8) using computational fluid dynamics based on subject-specific magnetic resonance imaging (MRI) measurements of the cervical spinal subarachnoid space. In addition, CTH was measured for each subject. Mean LI in the CMI group (551 ± 66 dyn/cm5) was significantly higher than in controls (220 ± 17 dyn/cm5, p < 0.001). Mean CTH in the CMI group was 9.0 ± 1.1 mm compared to -0.4 ± 0.5 mm in controls. Regression analysis of LI versus CTH found a weak relationship (R2 = 0.46, p < 0.001), demonstrating that CTH was not a good indicator of the impedance to CSF motion caused by cerebellar herniation. These results showed that CSF flow impedance was elevated in CMI patients and that LI provides different information than a standard CTH measurement. Further research is necessary to determine if LI can be useful in CMI patient diagnosis.

  6. Cerebrospinal fluid abnormalities in HIV-negative patients with secondary and early latent syphilis and serum VDRL ≥ 1:32

    OpenAIRE

    Maciej Pastuszczak; Jacek Zeman; Jaworek, Andrzej K; Anna Wojas-Pelc

    2013-01-01

    Background : Syphilis is caused by a spirochete Treponema pallidum. Invasion of the central nervous system (CNS) by T. pallidum may appear early during the course of disease. The diagnosis of confirmed neurosyphilis is based on the reactive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Recent studies indicated that serum RPR ≥ 1:32 are associated with higher risk of reactivity of CSF VDRL. Aims : The main aim of the current study was to assess cerebrospinal fluid s...

  7. The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer's but Not Parkinson's Disease or Dementia with Lewy Bodies.

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    Malin Wennström

    Full Text Available A major difference in the revised diagnostic criteria for Alzheimer's disease (AD is the incorporation of biomarkers to support a clinical diagnosis and allow the identification of preclinical AD due to AD neuropathological processes. However, AD-specific fluid biomarkers which specifically distinguish clinical AD dementia from other dementia disorders are still missing. Here we aimed to evaluate the disease-specificity of increased YKL-40 levels in cerebrospinal fluid (CSF from AD patients with mild to moderate dementia (n = 49 versus Parkinson's disease (PD (n = 61 and dementia with Lewy bodies (DLB patients (n = 36, and non-demented controls (n = 44. Second we aimed to investigate whether altered YKL-40 levels are associated with CSF levels of other inflammation-associated molecules. When correcting for age, AD patients exhibited 21.3%, 27.7% and 38.8% higher YKL-40 levels compared to non-demented controls (p = 0.0283, DLB (p = 0.0027 and PD patients (p<0.0001. The AD-associated increase in YKL-40 was not associated with CSF P-tau, T-tau or Aβ42. No relationship between increased YKL-40 and levels of the astrocytic marker glial-fibrillary acidic protein (GFAP, interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1 and interferon gamma-induced protein 10 (IP-10 could be identified. Our results confirm previous reports of an age-associated increased in CSF YKL-40 levels and further demonstrate increased CSF YKL-40 in AD patients versus non-demented controls and patients with DLB or PD. The increase in YKL-40 levels in the AD patients was unrelated to the established CSF AD biomarkers and the inflammatory markers GFAP, MCP-1, IP-10 and IL-8, proposing YKL-40 as a marker of yet to be identified AD-related pathological processes.

  8. Human Cervicovaginal Fluid Biomarkers to Predict Term and Preterm Labour

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    Yujing Jan Heng

    2015-05-01

    Full Text Available Preterm birth (PTB; birth before 37 completed weeks of gestation remains the major cause of neonatal morbidity and mortality. The current generation of biomarkers predictive of PTB have limited utility. In pregnancy, the human cervicovaginal fluid (CVF proteome is a reflection of the local biochemical milieu and is influenced by the physical changes occurring in the vagina, cervix and adjacent overlying fetal membranes. Term and preterm labour (PTL share common pathways of cervical ripening, myometrial activation and fetal membranes rupture leading to birth. We therefore hypothesise that CVF biomarkers predictive of labour may be similar in both the term and preterm labour setting. In this review, we summarise some of the existing published literature as well as our team’s breadth of work utilising the CVF for the discovery and validation of putative CVF biomarkers predictive of human labour.Our team established an efficient method for collecting serial CVF samples for optimal 2-dimensional gel electrophoresis resolution and analysis. We first embarked on CVF biomarker discovery for the prediction of spontaneous onset of term labour using 2D-electrophoresis and solution array multiple analyte profiling. 2D-electrophoretic analyses were subsequently performed on CVF samples associated with PTB. Several proteins have been successfully validated and demonstrate that these biomarkers are associated with term and PTL and may be predictive of both term and PTL. In addition, the measurement of these putative biomarkers was found to be robust to the influences of vaginal microflora and/or semen. The future development of a multiple biomarker bed-side test would help improve the prediction of PTB and the clinical management of patients.

  9. Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls – a hypothesis-generating pilot study

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    Bäckryd E

    2015-07-01

    Full Text Available Emmanuel Bäckryd,1,2 Bijar Ghafouri,1,2 Anders K Carlsson,1,2 Patrik Olausson,1,2 Björn Gerdle1,2 1Division of Community Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 2Pain and Rehabilitation Centre, Anaesthetics, Operations and Specialty Surgery Centre, Region Östergötland, Linköping, SwedenAbstract: Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11, and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients, two isoforms of alpha-1-antitrypsin (downregulated in patients, three isoforms of haptoglobin (upregulated in patients, and one isoform of pigment epithelium-derived factor (downregulated in patients. It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis

  10. Decreased cerebrospinal fluid levels of L-carnitine in non-apolipoprotein E4 carriers at early stages of Alzheimer's disease.

    Science.gov (United States)

    Lodeiro, María; Ibáñez, Clara; Cifuentes, Alejandro; Simó, Carolina; Cedazo-Mínguez, Ángel

    2014-01-01

    Increasing evidence suggest that Alzheimer's disease (AD) is a heterogeneous disorder that includes several subtypes with different etiology and progression. Cerebrospinal fluid (CSF) is being used to find new biomarkers reflecting the complexity of the pathological pathways within this disease. We used CSF and clinical data from patients to investigate the status of asymmetric dimethyl-L-arginine, creatine, suberylglycine, and L-carnitine along AD progression. These molecules play important roles in mitochondrial function and dysfunction in mitochondrial metabolism are involved in AD pathology. We found that non-APOE4 carriers show lower levels of L-carnitine in CSF early in AD. L-carnitine levels correlate with amyloid-β (Aβ) levels and Mini-Mental State Examination score, but do not add to the specificity or sensitivity of the classical AD CSF biomarkers, Aβ42, phospho-tau, and total-tau. Our results suggest APOE genotype-dependent differences in L-carnitine synthesis or metabolism along AD, and insinuate that L-carnitine treatments would be more beneficial for AD patients not carrying the APOE4 isoform.

  11. Cerebrospinal fluid abnormalities in HIV-negative patients with secondary and early latent syphilis and serum VDRL ≥ 1:32

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    Maciej Pastuszczak

    2013-01-01

    Full Text Available Background : Syphilis is caused by a spirochete Treponema pallidum. Invasion of the central nervous system (CNS by T. pallidum may appear early during the course of disease. The diagnosis of confirmed neurosyphilis is based on the reactive Venereal Disease Research Laboratory (VDRL in cerebrospinal fluid (CSF. Recent studies indicated that serum RPR ≥ 1:32 are associated with higher risk of reactivity of CSF VDRL. Aims : The main aim of the current study was to assess cerebrospinal fluid serological and biochemical abnormalities in HIV negative subjects with secondary and early latent syphilis and serum VDRL ≥ 1:32. Materials and Methods : Clinical and laboratory data of 33 HIV-negative patients with secondary and early latent syphilis, with the serum VDRL titer ≥ 1:32, who underwent a lumbar puncture and were treated in Department of Dermatology at Jagiellonian University School of Medicine in Cracow, were collected. Results : Clinical examination revealed no symptoms of CNS involvement in all patients. 18% ( n = 6 of patients met the criteria of confirmed neurosyphilis (reactive CSF-VDRL. In 14 (42% patients CSF WBC count ≥ 5/ul was found, and in 13 (39% subjects there was elevated CSF protein concentration (≥ 45 mg/dL. 10 patients had CSF WBC count ≥ 5/ul and/or elevated CSF protein concentration (≥ 45 mg/dL but CSF-VDRL was not reactive. Conclusions : Indications for CSF examination in HIV-negative patients with early syphilis are the subject of discussion. It seems that all patients with syphilis and with CSF abnormalities (reactive serological tests, elevated CSF WBC count, elevated protein concentration should be treated according to protocols for neurosyphilis. But there is a need for identification of biomarkes in order to identify a group of patients with syphilis, in whom risk of such abnormalities is high.

  12. Effect of Yishen Qiqiao Fang on dopamine content in serum and cerebrospinal fluid of patients in persistent vegetative statec

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: It has been demonstrated that the attack of persistent vegetative state is associated with the damaged neuron, which produces dopamine, and nervous pathway, the reduce of dopamine or malfunction of dopamine.OBJECTIVE: To observe the effect of self-made traditional Chinese medicine (TCM) Yishen Qiqiao Fang,which has the functions of supplementing qi and nourishing blood, resolving phlegm by promoting blood circulation, restoring consciousness and inducing resuscitation, on the contents of dopamine in serum and cerebrospinal fluid of patients in persistent vegetative state.DESIGN: An open randomized controlled clinical trial.SETTINGS: Nanjing University of Traditional Chinese Medicine, Nanjing Zijin Hospital.PARTICIPANTS: Thirty-eight inpatients of persistent vegetative state were selected from the Department of Neurology, Nanjing Zijin Hospital from August 2005 to November 2006. The patients were diagnosed according to the diagnostic standards set by the summary of a meeting for specialists in Nanjing. Informed contents were obtained from their relatives. According to the order of admission, the enrolled patients were divided into control group (n =20) and TCM treated group (n =20).METHODS: In the control group, the patients were treated with routine treatments for the symptoms. In the TCM treated group, the patients were treated with Yishen Qiqiao Fang besides the same treatments in the control group. TCM dispensing granules: each bag of mongolian milkvetch root, Chinese angelica and peach seed equaled to 10 g crude drug respectively; each bag of grassleaf sweetflag rhizome and dahurian angelica root equaled to 6 g crude drug respectively; Musk 0.05 g. The daily dosage for adults: 4 bags of mongolian milkvetch root, 2 bags of Chinese angelica, 0.05 g musk, 1 bag of peach seed, 2 bags of grassleaf sweetflag rhizome and 2 bags of dahurian angelica root, which should be given though nasal feeding or gastrostogavage before breakfast and supper every day

  13. Intraocular pressure and estimated cerebrospinal fluid pressure. The Beijing Eye Study 2011.

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    Ya Xing Wang

    Full Text Available PURPOSE: To examine a potential association between intraocular pressure (IOP and cerebrospinal fluid pressure (CSFP in a population-based setting. METHODS: The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50-93 years. A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP measurements, CSFP was calculated as CSFP [mm Hg] = 0.44×Body Mass Index [kg/m2]+0.16×Diastolic Blood Pressure [mm Hg]-0.18×Age [Years]. RESULTS: In multivariate analysis, IOP was associated with higher estimated CSFP (P<0.001; standardized correlation coefficient beta: 0.27; regression coefficient B: 0.20; 95% confidence interval (CI: 0.16, 0.24, after adjusting for thinner central corneal thickness (P<0.001; beta: 0.45; B: 0.04;95%CI: 0.04,0.04, smaller corneal curvature radius (P<0.001; beta:-0.11; B:-1.13;95%CI:-1.61,-0.64, shallower anterior chamber depth (P = 0.01; beta:-0.05; B:-0.33;95%CI:-0.59,-0.08 and longer axial length (P = 0.002; beta: 0.08; B: 0.20;95%CI: 0.08,0.32, and after adjusting for the systemic parameters of higher pulse rate (P<0.001; beta: 0.08; B: 0.02;95%CI: 0.01,0.03, higher prevalence of arterial hypertension (P = 0.002; beta: 0.06; B: 0.32;95%CI: 0.12,0.53, frequency of drinking alcohol (P = 0.02; beta: 0.04; B: 0.09;95%CI: 0.01,0.17, higher blood concentration of triglycerides (P = 0.001; beta: 0.06; B: 0.06;95%CI: 0.02,0.10 and cholesterol (P = 0.049; beta: 0.04; B: 0.08;95%CI: 0.00,0.17, and body mass index (P<0.001; beta:-0.13; B:-0.09;95%CI:-0.13,-0.06. In a parallel manner, estimated CSFP (mean: 10.8±3.7 mm Hg was significantly associated with higher IOP (P<0.001; beta: 0.13; B: 0.18;95%CI: 0.13,0.23 after adjusting for rural region of habitation (P<0.001; beta:-0.37; B:-2.78;95%CI:-3.07,-2.48, higher systolic blood pressure (P<0.001; beta: 0.34; B: 0.06;95%CI: 0.05,0.07, higher

  14. Líquido cefalorraqueano em 50 pacientes com AIDS Cerebrospinal fluid in 50 AIDS patients

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    S. L. Hinrichsen

    1996-06-01

    Full Text Available Foram estudados 50 pacientes com AIDS. Todos estes pacientes apresentavam anticorpos anti-HIV1 (ELISA e preenchiam os critérios de pontuação OPAS/Caracas de definição de casos de AIDS em adultos. A análise do liquido cefalorraqueano (LCR incluiu: pressão; citologia (número de células e aspectos citomorfológicos; proteína total e eletroforese; concentrações de glicose, cloretos e testes imunológicos para sífilis, toxoplasmose e infecções virais (citomegalovírus, varicela-zoster, Herpes simplex, e HI VI. Investigações bacteriológicas e micológicas (pesquisa direta e cultura, além de teste de aglutinação (látex para Cryptococcus foram também realizados. Os testes imunológicos usados foram fixação do complemento, imunofluorescência indireta, hemaglutinação passiva e/ou ELISA. Todos os LCR foram analisados no mesmo laboratório seguindo sempre a mesma metodologia. O LCR esteve alterado em 45 pacientes (90,0% dos 50 pacientes estudados. As principais alterações encontradas no LCR foram: aumento de gamaglobulina em 25 casos (55,5%; aumento da proteína total em 23 (51,1%; hipercitose em 22 (48,9% e diminuição dos cloretos em 18(40,0%. A detecção de anticorpos anti- HIV1 estiveram presentes em 42 pacientes (93,3%. Toxoplasmose isolada ou associada a outros agentes foi a infecção oportunista mais freqüente, detectada em 26 casos (57,7%. O LCR deverá ser sempre analisado em todos os pacientes com AIDS, com ou sem sintomas neurológicos.Fifty AIDS patients were studied. AH patients had anti-HIV antibodies (ELISA present and met OPAS/ Caracas punctuation criteria for AIDS cases in adults. Cerebrospinal fluid (CSF analysis included pressure, cytology (number and cytomorphological aspects, total protein and electrophoresis, glucose and chloride concentration. Bacteriological and mycological investigations were performed as well as agglutination tests for Cryptococcus. Complement fixation, indirect immunoflorescence

  15. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

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    Stopa Edward G

    2008-05-01

    Full Text Available Abstract This review integrates eight aspects of cerebrospinal fluid (CSF circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5, ion transporters (NaHCO3 cotransport, transport enzymes (isoforms of carbonic anhydrase, aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility, hydrodynamics (choroidal hypo- and hypersecretion and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor. In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF convection with both trophic

  16. In vitro study of cerebrospinal fluid dynamics in a shaken basal cistern after experimental subarachnoid hemorrhage.

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    Ulrich Kertzscher

    Full Text Available BACKGROUND: Cerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters. METHODOLOGY/PRINCIPAL FINDINGS: A model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force. CONCLUSIONS/SIGNIFICANCE: From this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space.

  17. Automatic Volumetry of the Cerebrospinal Fluid Space in Idiopathic Normal Pressure Hydrocephalus

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    Kazunari Ishii

    2013-12-01

    Full Text Available Objectives: To measure the cerebrospinal fluid (CSF space volume in idiopathic normal pressure hydrocephalus (INPH, we developed a software that allows us to automatically measure the regional CSF space and compared the volumes of the ventricle systems (VS, Sylvian fissures (SF and sulci at high convexity and midline (SHM among INPH patients, Alzheimer's disease (AD patients and healthy volunteers (HVs. Methods: Fifteen INPH patients, 15 AD patients and 15 HVs were retrospectively selected for this study. 3D-T1 MR images were obtained. We improved upon an automatic gray matter volume system to measure CSF spaces, adopting new regions for the template of INPH-characteristic CSF spaces and measured them. The VS, SF and SHM volumes were calculated relative to the intracranial volume. Results: The relative SHM volume of the INPH group (0.0237 ± 0.0064 was the smallest among the 3 groups (AD: 0.0477 ± 0.0109, HV: 0.0542 ± 0.0045. The VS (0.0499 ± 0.0135 and SF (0.0187 ± 0.0037 volumes of the INPH group were significantly larger than those of the AD (VS: 0.0311 ± 0.0075, SF: 0.0146 ± 0.0026 and HV groups (VS: 0.0167 ± 0.0065, SF: 0.0111 ± 0.017. Conclusion: Automatic volume measurement can be used to delineate the characteristic changes in CSF space in patients with INPH and is useful in the diagnosis of INPH.

  18. Transient leakage across the blood-cerebrospinal fluid barrier after intrathecal metrizamide administration to dogs

    International Nuclear Information System (INIS)

    Cerebrospinal fluid samples from 9 dogs given 84 mg of metrizamide/kg of body weight intrathecally were collected at intervals from 3 hours to 30 days after treatment and were compared with CSF samples collected before metrizamide treatment (base line) and with samples taken at similar intervals from 2 non treated control dogs. Increased CSF albumin (mean 19.2 mg/dl) and immunoglobulin (Ig) G (mean 5.91 mg/dl) concentrations occurred 1 day after myelography, compared with base-line concentrations (6.15 and 1.24 mg/dl, respectively) and with concentrations from controls. Immunoglobulin M and IgA concentrations also were increased in some of these samples. However, immediately after myelography (3 hours after treatment) CSF albumin and IgG concentrations were comparable with those of controls, and these values returned to base line within 5 days of myelography and remained so for 30 days. A high correlation between albumin and IgG concentrations of individual CSF samples indicated the likelihood that leakage across the blood-CSF barrier was the origin of the increased values. A transient increase in CSF leukocytes, consisting of mononuclear cells and neutrophils, was also noticed 1 day after treatment but not at other times and not in controls. Nonsuppurative, predominately histiocytic meningitis of decreasing intensity was noticed in dogs euthanatized at 1 or 5 days, but not in dogs euthanatized at 10, 20, or 30 days after treatment. The meningeal cells stained intensely with periodic acid-Schiff stain and intracellular contrast medium was ultrastructurally apparent in phagolysosomes. Control dogs killed after 30 days did not have these changes. The intrathecal administration of metrizamide resulted in transient leakage of serum components into CSF and an accompanying transient meningitis

  19. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain.

    Science.gov (United States)

    Manda, Prashanth; Kushwaha, Avadhesh Singh; Kundu, Santanu; Shivakumar, H N; Jo, Seong Bong; Murthy, S Narasimha

    2016-02-28

    The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h(-1). The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h(-1) and 0.42±0.10h(-1) respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain. PMID:26732557

  20. Cerebrospinal fluid adenosine deaminase activity: A complimentary tool in the early diagnosis of tuberculous meningitis

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    Taori Girdhar M

    2006-03-01

    Full Text Available Abstract Background Tuberculous meningitis (TBM is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB. The diagnosis of TBM is often difficult. A reliable, cost-effective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA activity in cerebrospinal fluid (CSF of TBM and non-TBM patients. Method ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. Results The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 ± 3.87 (2.99–26.94, mean ± SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 ± 2.14 (4.99–13.96 and from the non-infectious neurological disorders group, 2.71 ± 1.96 (0.00–7.68, P Conclusion This study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.

  1. The transport of L-6-fluorodopa and its metabolites from blood to cerebrospinal fluid and brain.

    Science.gov (United States)

    Hammerstad, J P; Pate, B D; Hewitt, K A; Chan, G L; Ruth, T J; Calne, D B

    1993-10-01

    The transport of L-6-fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of 18F-L-6-fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L-6-fluorodopa and its metabolites were determined in blood plasma and CSF by high-performance liquid chromatography. Raising the blood concentration of phenylalanine by intraperitoneal injection markedly reduced the accumulation of tracer in the brain. This indicates that L-6-fluorodopa and 3-O-methylfluorodopa, like native L-dopa and its O-methylated derivative, are transported at the brain capillary by the large neutral amino acid carrier-mediated system, which is subject to saturation and competition by other large neutral amino acids (such as phenylalanine) at physiological plasma concentrations. In contrast, administration of phenylalanine had no effect on the accumulation of tracer either in muscle, or as L-6-fluorodopa and 3-O-methylfluorodopa, in CSF. This suggests that the transport of L-dopa and its derivatives at the blood-CSF barrier differs from the transport at the blood-brain barrier and also that measurement of CSF L-dopa is not a good index of the transport and pharmacokinetics of L-dopa in the brain. However, the effect of phenylalanine administration in reducing the concentration of fluorohomovanillic acid in the CSF suggests that the concentration of homovanillic acid in the CSF is an accurate reflection of dopamine turnover in the brain. PMID:8215248

  2. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

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    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  3. Fructose levels are markedly elevated in cerebrospinal fluid compared to plasma in pregnant women.

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    Janice J Hwang

    Full Text Available Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000 th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS fructose production from glucose via the polyol pathway (glucose → sorbitol → fructose contributes to brain exposure to fructose.In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF, maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM undergoing spinal anesthesia and elective cesarean section.As expected, CSF glucose was ~ 60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001, and CSF sorbitol was ~ 9-times higher than plasma levels (p < 0.001. Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02 and sorbitol levels (ρ 0.75, p < 0.001. Cord blood sorbitol was also ~ 7-fold higher than maternal plasma sorbitol levels (p = 0.001. There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.

  4. Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects.

    Science.gov (United States)

    Ho, Emily L; Ronquillo, Rollie; Altmeppen, Hermann; Spudich, Serena S; Price, Richard W; Sinclair, Elizabeth

    2013-01-01

    In order to characterize the cellular composition of cerebrospinal fluid (CSF) in a healthy state and in the setting of chronic pleocytosis associated with HIV-1 (HIV) infection, multi-parameter flow cytometry was used to identify and quantitate cellular phenotypes in CSF derived from HIV-uninfected healthy controls and HIV-infected subjects across a spectrum of disease and treatment. CD4+ T cells were the most frequent CSF population and the CD4:CD8 ratio was significantly increased in the CSF compared to blood (p = 0.0232), suggesting preferential trafficking of CD4+ over CD8+ T cells to this compartment. In contrast, in HIV-infection, CD8+ T cells were the major cellular component of the CSF and were markedly increased compared to HIV-uninfected subjects (p<0.001). As with peripheral blood, the CSF CD4:CD8 ratio was reversed in HIV-infected subjects compared to HIV-uninfected subjects. Monocytes, B cells and NK cells were rare in the CSF in both groups, although absolute counts of CSF NK cells and B cells were significantly increased in HIV-infected subjects (p<0.05). Our studies show that T cells are the major cellular component of the CSF in HIV-infected and uninfected subjects. The CSF pleocytosis characteristic of HIV infection involves all lymphocyte subsets we measured, except for CD4+ T cells, but is comprised primarily of CD8+ T cells. The reduced proportion of CD4+ T cells in the CSF may reflect both HIV-related peripheral loss and changes in trafficking patterns in response to HIV infection in the central nervous system.

  5. Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects.

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    Emily L Ho

    Full Text Available In order to characterize the cellular composition of cerebrospinal fluid (CSF in a healthy state and in the setting of chronic pleocytosis associated with HIV-1 (HIV infection, multi-parameter flow cytometry was used to identify and quantitate cellular phenotypes in CSF derived from HIV-uninfected healthy controls and HIV-infected subjects across a spectrum of disease and treatment. CD4+ T cells were the most frequent CSF population and the CD4:CD8 ratio was significantly increased in the CSF compared to blood (p = 0.0232, suggesting preferential trafficking of CD4+ over CD8+ T cells to this compartment. In contrast, in HIV-infection, CD8+ T cells were the major cellular component of the CSF and were markedly increased compared to HIV-uninfected subjects (p<0.001. As with peripheral blood, the CSF CD4:CD8 ratio was reversed in HIV-infected subjects compared to HIV-uninfected subjects. Monocytes, B cells and NK cells were rare in the CSF in both groups, although absolute counts of CSF NK cells and B cells were significantly increased in HIV-infected subjects (p<0.05. Our studies show that T cells are the major cellular component of the CSF in HIV-infected and uninfected subjects. The CSF pleocytosis characteristic of HIV infection involves all lymphocyte subsets we measured, except for CD4+ T cells, but is comprised primarily of CD8+ T cells. The reduced proportion of CD4+ T cells in the CSF may reflect both HIV-related peripheral loss and changes in trafficking patterns in response to HIV infection in the central nervous system.

  6. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy.

    Science.gov (United States)

    Ribera, Albert; Haurigot, Virginia; Garcia, Miguel; Marcó, Sara; Motas, Sandra; Villacampa, Pilar; Maggioni, Luca; León, Xavier; Molas, Maria; Sánchez, Víctor; Muñoz, Sergio; Leborgne, Christian; Moll, Xavier; Pumarola, Martí; Mingozzi, Federico; Ruberte, Jesús; Añor, Sònia; Bosch, Fatima

    2015-04-01

    Gene therapy is an attractive tool for the treatment of monogenic disorders, in particular for lysosomal storage diseases (LSD) caused by deficiencies in secretable lysosomal enzymes in which neither full restoration of normal enzymatic activity nor transduction of all affected cells are necessary. However, some LSD such as Mucopolysaccharidosis Type IIIB (MPSIIIB) are challenging because the disease's main target organ is the brain and enzymes do not efficiently cross the blood-brain barrier even if present at very high concentration in circulation. To overcome these limitations, we delivered AAV9 vectors encoding for α-N-acetylglucosaminidase (NAGLU) to the Cerebrospinal Fluid (CSF) of MPSIIIB mice with the disease already detectable at biochemical, histological and functional level. Restoration of enzymatic activity in Central Nervous System (CNS) resulted in normalization of glycosaminoglycan content and lysosomal physiology, resolved neuroinflammation and restored the pattern of gene expression in brain similar to that of healthy animals. Additionally, transduction of the liver due to passage of vectors to the circulation led to whole-body disease correction. Treated animals also showed reversal of behavioural deficits and extended lifespan. Importantly, when the levels of enzymatic activity were monitored in the CSF of dogs following administration of canine NAGLU-coding vectors to animals that were either naïve or had pre-existing immunity against AAV9, similar levels of activity were achieved, suggesting that CNS efficacy would not be compromised in patients seropositive for AAV9. Our studies provide a strong rationale for the clinical development of this novel therapeutic approach as the treatment for MPSIIIB. PMID:25524704

  7. The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord.

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    Petracca, Yanina L; Sartoretti, Maria Micaela; Di Bella, Daniela J; Marin-Burgin, Antonia; Carcagno, Abel L; Schinder, Alejandro F; Lanuza, Guillermo M

    2016-03-01

    Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. PMID:26839365

  8. Role of the RVM in Descending Pain Regulation Originating from the Cerebrospinal Fluid-Contacting Nucleus.

    Science.gov (United States)

    Fei, Yan; Wang, Xin; Chen, Songsong; Zhou, Qiangqiang; Zhang, Chao; Li, Ying; Sun, Lihong; Zhang, Licai

    2016-07-01

    Evidence has suggested that cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) is correlated with the development and recurrence of pain. A recent research showed that the CSF-contacting nucleus acts as a component of the descending 5-hydroxytryptamine (5-HT) system and plays a role in descending pain inhibition. However, limited studies are conducted to investigate the relationship between the CSF-contacting nucleus and pain. In present study, we explored the effect of CSF-contacting nucleus on nociceptive behaviors in both normal and neuropathic rats via targeted ablation of the CSF-contacting nucleus in the brainstem, using cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. The CB-SAP-treated rats showed aggravated thermal hyperalgesia and mechanical allodynia. Also, results from immunohistochemical experiments showed that rostral ventromedial medulla (RVM) received fiber projection from the CSF-contacting nucleus, which disappeared after ablation of the CSF-contacting nucleus, and the CB-SAP treated rats showed downregulation of c-Fos expression in the RVM as compared with the rats receiving i.c.v. injection of phosphate buffer saline (PBS). A significant downregulation of 5-HT-labeled neurons and tryptophan hydroxylase 2 (TPH2) as the marker of 5-HT cells in the RVM, and 5-HT expression in spinal dorsal horn in both normal and chronic constriction injury (CCI) rats after i.c.v. injection of CB-SAP was observed. These results suggested that RVM may be involved in descending pain modulation originating from the CSF-contacting nucleus. PMID:26961890

  9. Cerebrospinal fluid analysis, predictors of bacterial meningitis: a study in 312 patients with suspected meningial infection

    Institute of Scientific and Technical Information of China (English)

    Seyed Mohammad Alavi; Naser Moshiri

    2009-01-01

    Objective:Patients with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis (BM). The aim of this study was to evaluate predictors to dif-ferentiate BM from aseptic meningitis (ASM). Methods:The study was conducted in Razi hospital, a training center affiliated to Ahvaz Joundishapoor University of Medical Sciences in Iran. And all patients were 18 years old or above and were treated in the hospital between 2003 and 2007. Data of those who had meningitis, tested as CSF pleocytosis but had not received antibiotic treatment before lumbar puncture were retrospectively analyzed. Results: Among 312 patients with CSF pleocytosis, two hundred fifteen (68.9%) had BM and ninety seven (31.1%) had ASM. The mean age for patients with BM was (34.7±17.7) years (P=0.22, NS). Sixty percent of the BM cases and 61.2% of the ASM cases occurred in men (P=0.70, NS). We identified the following predictors of BM:CSF-WBC count > 100 per micro liter, CSF-glucose level 80 mg/dL. Sensitivity, specificity, PPV, NPV of these predictors, and LR for BM are 86.5% ,52.6% ,80.2%, 63.7% and 104. 1 for CSF-WBC count and 72.1%, 83.5%, 90.6% ,57.4% and 164.2% for CSF glucose, and 49.7%, 91.8%, 93.4% ,45. 2% and 104.5% for CSF protein. Conclusion:The CSF WBC count should not be used alone to rule out bacterial meningitis. When it is combined with other factors such as CSF glucose and protein improved decision making in patients with suspected BM may occur.

  10. BAFF is decreased in the cerebrospinal fluid of multiple sclerosis at clinical onset.

    Science.gov (United States)

    Puthenparampil, M; Miante, S; Federle, L; Zanetta, C; Toffanin, E; Ruggero, S; Rinaldi, F; Gallo, P

    2016-08-15

    B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset. Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, QBAFF) and Index (QBAFF/QAlb, BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (p<0.05). BAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (p<0.01). A significant inverse correlation between QIgG and QBAFF (r: -0.4, p<0.05) and between BAFF index and IgGIF (r: -0.4, p<0.05) or IgG Index (r: -0.4, p=0.05) was found in IgGOB+. The decreased CSF levels of BAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. PMID:27397077

  11. Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

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    Cecchini Diego M

    2009-11-01

    Full Text Available Abstract Background The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1 CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer; (2 CSF HIV-1 viral load and HIV-1 plasma viral load; and (3 CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. Methods Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006. We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche. Data were processed with Statistix 7.0 software (linear regression analysis. Results Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01. No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123. Conclusion Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

  12. Season of sampling and season of birth influence serotonin metabolite levels in human cerebrospinal fluid.

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    Jurjen J Luykx

    Full Text Available BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF monoamine (MA turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA, dopamine (homovanillic acid, HVA and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG were measured using high performance liquid chromatography (HPLC. Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75. The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050, with predicted maximum (PC(max and minimum (PC(min concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max = 172 and PC(min = 126. The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall.

  13. Analysis of cerebro-spinal fluid protein composition in early developmental stages in chick embryos.

    Science.gov (United States)

    Gato, A; Martín, P; Alonso, M I; Martín, C; Pulgar, M A; Moro, J A

    2004-04-01

    Foetal cerebro-spinal fluid (CSF) has a very high protein concentration when compared to adult CSF, and in many species five major protein fractions have been described. However, the protein concentration and composition in CSF during early developmental stages remains largely unknown. Our results show that in the earliest stages (18 to 30 H.H.) of chick development there is a progressive increase in CSF protein concentration until foetal values are attained. In addition, by performing electrophoretic separation and high-sensitivity silver staining, we were able to identify a total of 21 different protein fractions in the chick embryo CSF. In accordance with the developmental pattern of their concentration, these can be classified as follows: A: high-concentration fractions which corresponded with the ones described in foetal CSF by other authors; B: low-concentration fractions which remained stable throughout the period studied; C: low-concentration fractions which show changes during this period. The evolution and molecular weight of the latter group suggest the possibility of an important biological role. Our data demonstrate that all the CSF protein fractions are present in embryonic serum; this could mean that the specific transport mechanisms in neuroepithelial cells described in the foetal period evolve in very early stages of development. In conclusion, this paper offers an accurate study of the protein composition of chick embryonic CSF, which will help the understanding of the influences on neuroepithelial stem cells during development and, as a result, the appropriate conditions for the in vitro study of embryonic/foetal nervous tissue cells. PMID:15039986

  14. Insulin resistance is associated with higher cerebrospinal fluid tau levels in asymptomatic APOE ε4 carriers

    Science.gov (United States)

    Starks, Erika J.; O'Grady, J. Patrick; Hoscheidt, Siobhan M.; Racine, Annie M.; Carlsson, Cindy M.; Zetterberg, Henrik; Blennow, Kaj; Okonkwo, Ozioma C.; Puglielli, Luigi; Asthana, Sanjay; Dowling, N. Maritza; Gleason, Carey E.; Anderson, Rozalyn M.; Davenport-Sis, Nancy J.; DeRungs, LeAnn M.; Sager, Mark A.; Johnson, Sterling C.; Bendlin, Barbara B.

    2015-01-01

    Background Insulin resistance (IR) is linked with the occurrence of pathological features observed in Alzheimer's disease (AD), including neurofibrillary tangles and amyloid plaques. However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear. Objective To determine the extent to which IR is linked with amyloid and tau pathology in late-middle-age. Method Cerebrospinal fluid (CSF) samples collected from 113 participants enrolled in the Wisconsin Registry for Alzheimer's Prevention study (mean age = 60.6 years), were assayed for AD-related markers of interest: Aβ42, P-Tau181, and T-Tau. IR was determined using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Linear regression was used to test the effect of IR, and APOE ε4, on tau and amyloid pathology. We hypothesized that greater IR would be associated with higher CSF P-Tau181 and T-Tau, and lower CSF Aβ42. Results No significant main effects of HOMA-IR on P-Tau181, T-Tau, or Aβ42 were observed; however, significant interactions were observed between HOMA-IR and APOE ε4 on CSF markers related to tau. Among APOE ε4 carriers, higher HOMA-IR was associated with higher P-Tau181 and T-Tau. Among APOE ε4 non-carriers, HOMA-IR was negatively associated with P-Tau181 and T-Tau. We found no effects of IR on Aβ42 levels in CSF. Conclusion IR among asymptomatic APOE ε4 carriers was associated with higher P-Tau181 and T-Tau in late-middle age. The results suggest that IR may contribute to tau-related neurodegeneration in preclinical AD. The findings may have implications for developing prevention strategies aimed at modifying IR in mid-life. PMID:25812851

  15. Effect of the drainage of cerebrospinal fluid in patients with aneurismal subarachnoid hemorrhage

    Science.gov (United States)

    Qian, Cong; Yu, Xiaobo; Chen, Jingyin; Gu, Chi; Wang, Lin; Chen, Gao; Dai, Yuying

    2016-01-01

    Abstract Background and objectives: Vasospasm-related injury such as delayed ischemic neurological defect (DIND) or cerebral infarction is an important prognostic factor for aneurismal subarachnoid hemorrhage (SAH). Whether cerebrospinal fluid (CSF) drainage can achieve a better outcome in aneurismal SAH patients after coiling or clipping remains the subject of debate. Here, we report a meta-analysis of the related available literature to assess the effect of continuous CSF drainage on clinical outcomes in patients with aneurismal SAH. Methods: Case-control studies regarding the association between aneurismal SAH and CSF drainage were systematically identified through online databases (PubMed, Web of Science, Elsevier Science Direct, and Springer Link). Inclusion and exclusion criteria were defined for the eligible studies. The fixed-effects model was performed when homogeneity was indicated. Alternatively, the random-effects model was utilized. Results: This meta-analysis included 11 studies. Continuous CSF drainage obviously improved patients’ long-term outcome (odds ratio [OR] of 2.86, 95% confidence interval [CI], 1.37–5.98, P hydrocephalus (SDHC) prevention (OR of 1.04, 95% CI, 0.52–2.07, P = 0.91). Further analysis on lumbar drainage (LD) and external ventricular drainage (EVD) indicated that LD had a better outcome (OR of 3.11, 95% CI, 1.18–8.23, P = 0.02), whereas no significant difference in vasospasm-related injury was detected between the groups (OR of 1.13, 95% CI, 0.54–2.37, P = 0.75). Conclusion: Continuous CSF drainage is an effective treatment for aneurismal SAH patients; lumbar drainage showed lower complications, but more well-designed studies are required to verify and consolidate this conclusion. PMID:27741143

  16. Incorporating and Compensating Cerebrospinal Fluid in Surface-Based Forward Models of Magneto- and Electroencephalography

    Science.gov (United States)

    Stenroos, Matti; Nummenmaa, Aapo

    2016-01-01

    MEG/EEG source imaging is usually done using a three-shell (3-S) or a simpler head model. Such models omit cerebrospinal fluid (CSF) that strongly affects the volume currents. We present a four-compartment (4-C) boundary-element (BEM) model that incorporates the CSF and is computationally efficient and straightforward to build using freely available software. We propose a way for compensating the omission of CSF by decreasing the skull conductivity of the 3-S model, and study the robustness of the 4-C and 3-S models to errors in skull conductivity. We generated dense boundary meshes using MRI datasets and automated SimNIBS pipeline. Then, we built a dense 4-C reference model using Galerkin BEM, and 4-C and 3-S test models using coarser meshes and both Galerkin and collocation BEMs. We compared field topographies of cortical sources, applying various skull conductivities and fitting conductivities that minimized the relative error in 4-C and 3-S models. When the CSF was left out from the EEG model, our compensated, unbiased approach improved the accuracy of the 3-S model considerably compared to the conventional approach, where CSF is neglected without any compensation (mean relative error 40%). The error due to the omission of CSF was of the same order in MEG and compensated EEG. EEG has, however, large overall error due to uncertain skull conductivity. Our results show that a realistic 4-C MEG/EEG model can be implemented using standard tools and basic BEM, without excessive workload or computational burden. If the CSF is omitted, compensated skull conductivity should be used in EEG. PMID:27472278

  17. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

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    Vasilii B Doronin

    Full Text Available We have recently shown that IgGs from serum and cerebrospinal fluid (CSF of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.

  18. Serum and cerebrospinal fluid concentrations of E-selectin in patients with aneurysmal subarachnoid hemorrhage

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    T. Tanriverdi

    2005-11-01

    Full Text Available The goal of the present study was to determine concentrations of E-selectin in both cerebrospinal fluid (CSF and serum of patients with aneurysmal subarachnoid hemorrhage (SAH and to evaluate the correlation between the clinical parameters and E-selectin levels. Both CSF and serum samples obtained from 12 patients with aneurysmal SAH and 8 patients with hydrocephalus (control group without any other known central nervous system disease were assayed for E-selectin by quantitative enzyme-linked immunosorbent assay and the results were compared between the two groups. Mean levels of soluble forms of E-selectin within the first 3 days and on the 5th and 7th days of SAH were 4.0 ± 7.9, 2.8 ± 5.2, and 3.1 ± 4.9 ng/ml in the patient's CSF, and 33.7 ± 9.2, 35.1 ± 7.0, and 35.2 ± 8.7 ng/ml in serum, respectively. In contrast, mean E-selectin levels were 0.1 ± 0.2 ng/ml in CSF and 8.7 ± 5.0 ng/ml in serum of control patients. The difference between groups was statistically significant regarding both CSF and serum E-selectin levels (P < 0.05. Thus, we have demonstrated a marked increase of E-selectin concentration in both CSF and serum of patients with aneurysmal SAH compared with control and suggest that blocking the interaction between E-selectin and vascular endothelium may have a beneficial effect on vasospasms.

  19. A tomographic study of the skull base in primary spontaneous cerebrospinal fluid leaks

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    Giannetti, Alexandre Varella [Hospital das Clinicas, Service of Neurosurgery, Belo Horizonte (Brazil); Federal University of Minas Gerais, Department of Surgery, School of Medicine, Belo Horizonte (Brazil); Guimaraes, Roberto Eustaquio S. [Hospital das Clinicas, Services Otorhinolaryngology, Belo Horizonte (Brazil); Federal University of Minas Gerais, Department of Ophthalmology and Otorhinolaryngology, School of Medicine, Belo Horizonte (Brazil); Santiago, Ana Paula M.S. [Hospital das Clinicas, Services Radiology, Belo Horizonte (Brazil); Perpetuo, Francisco Otaviano L.; Machado, Marco Antonio O. [Computed Tomography Center of Minas Gerais, Belo Horizonte (Brazil)

    2012-05-15

    This study aims to evaluate the existence of anatomic abnormalities in the skull base that could contribute to the origin of primary spontaneous cerebrospinal fluid leaks (PSL). Twenty PSL patients were compared with 20 healthy individuals. The following features were measured through an analysis of computed tomography scans: the angles of the petrosal bones and skull base in both the sagittal and coronal planes; the anteroposterior and mediolateral diameters of the anterior skull base, sella, and sphenoid sinus; the depth of the olfactory fossa; the pneumatization of the sphenoid sinus; the position of the crista galli; and the state of the dorsum sellae. Body mass index (BMI) was compared. There were no differences between the two groups with respect to the angles and diameters of the anterior cranial fossa and the sphenoid sinus or the depth of the olfactory fossa. Pneumatization of the lateral recess of the sphenoid sinus was more frequent in the PSL group (55%) than in the control group (25%, p = 0.053). The dorsum sellae were eroded in 30% of the PSL patients but intact in all healthy subjects. PSL subjects showed higher sellae (1.0 versus 0.8 cm, p = 0.002). The average BMI of PSL patients was higher than that of the control group. Global alterations in the skull base of PSL patients were not found. The increase in the height of sellae and the erosion of its dorsum suggest intracranial hypertension. The higher BMI in the case group confirms the relation between obesity and PSL. (orig.)

  20. Cerebrospinal Fluid Hypocretin-1 (Orexin-A Level Fluctuates with Season and Correlates with Day Length.

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    Kim Boddum

    Full Text Available The hypocretin/orexin neuropeptides (hcrt are key players in the control of sleep and wakefulness evidenced by the fact that lack of hcrt leads to the sleep disorder Narcolepsy Type 1. Sleep disturbances are common in mood disorders, and hcrt has been suggested to be poorly regulated in depressed subjects. To study seasonal variation in hcrt levels, we obtained data on hcrt-1 levels in the cerebrospinal fluid (CSF from 227 human individuals evaluated for central hypersomnias at a Danish sleep center. The samples were taken over a 4 year timespan, and obtained in the morning hours, thus avoiding impact of the diurnal hcrt variation. Hcrt-1 concentration was determined in a standardized radioimmunoassay. Using biometric data and sleep parameters, a multivariate regression analysis was performed. We found that the average monthly CSF hcrt-1 levels varied significantly across the seasons following a sine wave with its peak in the summer (June-July. The amplitude was 19.9 pg hcrt/mL [12.8-26.9] corresponding to a 10.6% increase in midsummer compared to winter. Factors found to significantly predict the hcrt-1 values were day length, presence of snow, and proximity to the Christmas holiday season. The hcrt-1 values from January were much higher than predicted from the model, suggestive of additional factors influencing the CSF hcrt-1 levels such as social interaction. This study provides evidence that human CSF hcrt-1 levels vary with season, correlating with day length. This finding could have implications for the understanding of winter tiredness, fatigue, and seasonal affective disorder. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation.

  1. Cerebrospinal fluid hypovolemia in childhood and adolescence. Clinical features and outcomes

    International Nuclear Information System (INIS)

    Cerebrospinal fluid (CSF) hypovolemia has increasingly been recognized, but few investigations have examined younger patients. This study investigated 50 cases of CSF hypovolemia onset in childhood and adolescence. We analyzed causes, outcomes, and clinical features of these child and adolescent CSF hypovolemia cases. The 50 patients (25 boys, 25 girls) had shown the onset earlier than age 15. Diagnosis of probable CSF hypovolemia was made basically on clinical symptoms and findings of magnetic resonance imaging (MRI) and Radioisotope (RI) cisternography. For treatment, we defined epidural blood patch (EBP) indication as the early bladder filling (early BF) and all of the 50 cases received EBP. All patients suffered from one or more symptoms such as intractable headache, neck pain, vertigo, fatigue, tinnitus and visual disturbance. These symptoms did not recover with any conventional treatments. Twenty eight cases (56.0%) showed normal results on MRI. In RI cisternography, 16 cases (32.0%) showed CSF leaks (CL), 34 cases (68.0%) showed early BF. About 90% of the patients were improved by EBP. In particular, 96.0% of cases showed good or moderate recovery when onset of CSF hypovolemia and the first treatment was less than 1 year. CSF hypovolemia is not yet well recognized particularly in child and adolescent cases. Some children were misdiagnosed as autonomic nervous system dysfunction, orthostatic dysregulation, Barre-Lieou syndrome or depression. This study indicated that EBP is also effective for younger patients. If patients suffer from various intractable symptoms including orthostatic headache, CSF hypovolemia should be considered for the differential diagnosis. (author)

  2. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

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    Petropoulos Christos J

    2005-11-01

    Full Text Available Abstract Background Central nervous system (CNS exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1 progression of systemic infection, 2 CSF white blood cell (WBC count, 3 antiretroviral therapy (ART, and 4 neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL. CSF HIV viral loads (VLs correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

  3. Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary progressive multiple sclerosis.

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    Marcel P Stoop

    Full Text Available BACKGROUND: Based on clinical representation of disease symptoms multiple sclerosis (MScl patients can be divided into two major subtypes; relapsing remitting (RR MScl (85-90% and primary progressive (PP MScl (10-15%. Proteomics analysis of cerebrospinal fluid (CSF has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. METHODOLOGY/PRINCIPAL FINDINGS: CSF samples (n = 31 were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA as differentially abundant in the comparison between both MScl types. CONCLUSIONS/SIGNIFICANCE: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.

  4. Analysis of clinical features, serologic and cerebrospinal fluid tests in patients with neurosyphilis at different stages

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    Bao-jie WANG

    2016-08-01

    Full Text Available Objective To summarize the clinical features, serologic, cerebrospinal fluid (CSF tests in patients with neurosyphilis at different stages.  Methods A retrospective analysis was made on the clinical features, imaging, serologic and CSF tests, treatment and prognosis of 12 cases diagnosed as neurosyphilis. In those cases, 5 cases were early-stage neurosyphilis, including 4 syphilitic meningitis (meningomyelitis and one meningovascular syphilis; 7 cases were late-stage neurosyphilis, all of whom were general paresis.  Results The serum Treponema pallidum antibody (TP-Ab and rapid plasma regain (RPR tests were positive in all 12 cases. The CSF TP-Ab tests of 12 cases were all positive and CSF RPR tests were positive in 9 cases. In 5 cases of early-stage neurosyphilis, one case had elevated intracranial pressure (ICP, 3 cases presented with elevated white blood cell (WBC, 4 cases had elevated protein concentration. In 7 cases of late-stage neurosyphilis, one case had elevated ICP, 7 cases presented with elevated WBC and protein concentration. CSF cytology showed lymphocyte reaction, mainly small lymphocytes. All cases were treated with different doses of intravenous penicillin or ceftriaxone sodium by intramuscular injection, among whom 8 cases presented improved neuropsychiatric symptoms, while 4 cases had no significant improvement.  Conclusions Neurosyphilis is easy to be misdiagnosed because of various styles of onset and nontypical clinical manifestations. A definite diagnosis depends on clinical manifestations and serologic and CSF examinations. Early diagnosis and standard treatment is essential for improving prognosis and reducing complications. DOI: 10.3969/j.issn.1672-6731.2016.07.005

  5. Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress.

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    Wu, Yue-Hong; Song, Si-Yuan; Liu, He; Xing, Dan; Wang, Xin; Fei, Yan; Li, Guang-Ling; Zhang, Chao; Li, Ying; Zhang, Li-Cai

    2015-06-01

    The contribution of the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) and adrenomedullin (ADM) to the developmental modulation of stressful events remains controversial. This study explored the effects of endogenous ADM in the CSF-contacting nucleus on immobilization of stress-induced physiological parameter disorders and glucocorticoid hormone releasing hormone (CRH), rat plasma corticosterone expression, and verification of such effects by artificially lowering ADM expression in the CSF-contacting nucleus by targeted ablation of the nucleus. Immunohistochemical experiments showed that ADM-like immunoreactivity and the calcitonin receptor-like receptor (CRLR) marker were localized in the CSF-contacting nucleus. After 7 continuous days of chronic immobilization stress (CIS), animals exhibited anxiety-like behavior. Also, an increase in serum corticosterone, and enhanced expression of ADM in the CSF-contacting nucleus were observed, following activation by CIS. The intracerebroventricular (i.c.v.) administration of the ADM receptor antagonist AM22-52 significantly reduced ADM in the CSF-contacting nucleus, additionally, blocked the effects of ADM, meaning the expression of CRH in the hypothalamic paraventricular nucleus (Pa) and serum corticosterone level were increased, and the physiological parameters of the rats became correspondingly deteriorated. Additionally, the i.c.v. administration of cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to a cholera toxin subunit, completely eliminated the CSF-contacting nucleus, worsening the reaction of the body to CIS. The collective results demonstrated that ADM acted as a stress-related peptide in the CSF-contacting nucleus, and its lower expression and blocked effects in the nucleus contributed to the deterioration of stress-induced physiologic parameter disorders as well as the excessive expressions of stress-related hormones which were part of the hypothalamic-pituitary-adrenal (HPA) axis

  6. Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume.

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    Hamilton, Robert; Baldwin, Kevin; Fuller, Jennifer; Vespa, Paul; Hu, Xiao; Bergsneider, Marvin

    2012-11-01

    This study identifies a novel relationship between cerebrospinal fluid (CSF) stroke volume through the cerebral aqueduct and the characteristic peaks of the intracranial pulse (ICP) waveform. ICP waveform analysis has become much more advanced in recent years; however, clinical practice remains restricted to mean ICP, mainly due to the lack of physiological understanding of the ICP waveform. Therefore, the present study set out to shed some light on the physiological meaning of ICP morphological metrics derived by the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating their relationships with a well defined physiological variable, i.e., the stroke volume of CSF through the cerebral aqueduct. Seven patients received both overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological analysis of the ICP signal was performed by the MOCAIP algorithm. Following extraction of morphological metrics from the ICP signal, nine temporal ICP metrics and two amplitude-based metrics were compared with the ASV via Spearman's rank correlation. Of the nine temporal metrics correlated with the ASV, only the width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP pulse pressure amplitude and mean ICP did not reach significance. In this study, we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is positively related to the volume of CSF movement through the cerebral aqueduct. This finding is an initial step in bridging the gap between ICP waveform morphology research and clinical practice.

  7. Risk factors for postoperative cerebrospinal fluid leak and meningitis after expanded endoscopic endonasal surgery.

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    Ivan, Michael E; Iorgulescu, J Bryan; El-Sayed, Ivan; McDermott, Michael W; Parsa, Andrew T; Pletcher, Steven D; Jahangiri, Arman; Wagner, Jeffrey; Aghi, Manish K

    2015-01-01

    Postoperative cerebrospinal fluid (CSF) leak is a serious complication of transsphenoidal surgery, which can lead to meningitis and often requires reparative surgery. We sought to identify preoperative risk factors for CSF leaks and meningitis. We reviewed 98 consecutive expanded endoscopic endonasal surgeries performed from 2008-2012 and analyzed preoperative comorbidities, intraoperative techniques, and postoperative care. Univariate and multivariate analyses were performed. The most common pathologies addressed included pituitary adenoma, Rathke cyst, chordoma, esthesioneuroblastoma, meningioma, nasopharyngeal carcinoma, and squamous cell carcinoma. There were 11 CSF leaks (11%) and 10 central nervous system (CNS) infections (10%). Univariate and multivariate analysis of preoperative risk factors showed that patients with non-ideal body mass index (BMI) were associated with higher rate of postoperative CSF leak and meningitis (both p<0.01). Also, patients with increasing age were associated with increased CSF leak (p = 0.03) and the length of time a lumbar drain was used postoperatively was associated with infection in a univariate analysis. In addition, three of three endoscopic transsphenoidal surgeries combined with open cranial surgery had a postoperative CSF leak and CNS infection rate which was a considerably higher rate than for transsphenoidal surgeries alone or surgeries staged with open cases (p<0.01 and p=0.04, respectively) In this series of expanded endoscopic transsphenoidal surgeries, preoperative BMI remains the most important preoperative predictor for CSF leak and infection. Other risk factors include age, intraoperative CSF leak, lumbar drain duration, and cranial combined cases. Risks associated with complex surgical resections when combining open and endoscopic approaches could be minimized by staging these procedures.

  8. Human cerebrospinal fluid fatty acid levels differ between supernatant fluid and brain-derived nanoparticle fractions, and are altered in Alzheimer's disease.

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    Alfred N Fonteh

    Full Text Available Although saturated (SAFA, monounsaturated (MUFA, and polyunsaturated (PUFA fatty acids are important structural components of neuronal membranes and precursors of signaling molecules, knowledge of their metabolism in Alzheimer's disease (AD is limited. Based on recent discovery that lipids in cerebrospinal fluid (CSF are distributed in both brain-derived nanoparticles (NP and supernatant fluid (SF, we hypothesized that fatty acid (FA abundance and distribution into these compartments is altered in early AD pathology.We assayed the FA composition and abundance in CSF fractions from cognitively healthy (CH, mild cognitive impairment (MCI, and AD study participants using gas chromatography-mass spectrometry. In the SF fraction, concentration of docosahexaenoic acid [DHA, (C22:6n-3] was less in AD compared with CH, while alpha linolenic acid [α-LNA, (C18:3n-3] was lower in MCI compared with CH. In the NP fraction, levels of SAFAs (C15:0, C16:0 and a MUFA (C15:1 differentiated CH from MCI, while two MUFAs (C15:1, C19:1 and four PUFAs (C20:2n-6, C20:3n-3, C22:4n-6, C22:5n-3 were higher in AD compared with CH. Levels of even-chain free SAFA and total free FA levels were higher in AD, levels of odd-chain free SAFAs, MUFAs, n-3 PUFAs, and total PUFA, were lower in AD compared with CH. Free n-6 PUFA levels were similar in all three groups.FA metabolism is compartmentalized differently in NP versus SF fractions of CSF, and altered FA levels reflect the importance of abnormal metabolism and oxidative pathways in AD. Depleted DHA in CSF fractions in AD is consistent with the importance of n-3 PUFAs in cognitive function, and suggests that disturbed PUFA metabolism contributes to AD pathology. This study of FA levels in CSF fractions from different cognitive stages shows potential AD biomarkers, and provides further insight into cell membrane dysfunctions, including mechanisms leading to amyloid production.

  9. Alterations in amyloid beta-protein and apolipoprotein E in cerebrospinal fluid after subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Xinzhong Wen; Yonghong Zhang; Leiming Huo

    2007-01-01

    BACKGROUND: The findings about the alterations in cerebrospinal fluid beta-amyloid protein (Aβ) and apolipoprotein E (ApoE) after subarachnoid hemorrhage indicate that they have significant correlation with prognosis of patients.OBJECTIVE: To observe the alterations in cerebrospinal fluid Aβ and ApoE after subarachnoid hemorrhage (SAH).DESIGN: Contrast observation.SETTING: Department of Neurosurgery, the First Hospital of Lanzhou University.PARTICIPANTS: A total of 25 SAH patients including 16 males and 9 females aged from 13 to 72 years were selected form Department of Neurosurgery, the First Affiliated Hospital of Lanzhou University from October 2003 to February 2004. The Hunt-Hess grade ranged from Ⅰ to Ⅳ, and patients admitted hospital in 24 hours after invasion, affirmed by the brain CT scan and lumbar vertebra puncture, no other severe complications and important organs' functional defect and severe infection, no hematological system disease.METHODS: All admitted patients were collected CSF by lumbar vertebra puncture in 24 hours. The cerebrospinal fluid (CSF) of control group came from the admitted 15 patients of our hospital that have no nervous system disease. Aβ content was detected by enzyme linked immunosorbent assay (ELISA), the kit was provided by the Central Laboratory of the First Hospital of Lanzhou University; ApoE concentration was detected by monoclone enzyme linked immunosorbent assay (ELISA), the kit was provided by the Immunotechnique Research Institute of the Fourth Military Medical University. S100B concentration was detected by enzyme linked immunosorbent assay double antibody sandwich method, the kit was provided by the Physiological Research Room of the Fourth Military Medical University. The data were indicated on Mean±SD and were analyzed by SPSS 10.0 statistical package. All data were handled through test of significance variance analysis, and groups were compared through independent sampler t test. The concentration was

  10. Impact of cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus on the amyloid cascade.

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    Masao Moriya

    Full Text Available The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF flow dynamics by CSF shunting, can suppress the oligomerization of amyloid β-peptide (Aβ, by measuring the levels of Alzheimer's disease (AD-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH (samples were obtained before and 1 year after shunting, 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived Aβ-like peptides (APL1β (a surrogate marker for Aβ. We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP and Aβ38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ≥ 1 on the modified Rankin Scale and unfavorable (no improvement on the modified Rankin Scale outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in Aβ38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1β25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPPα and sAPPβ, Aβ38 and 42, and APL1β25 and 28, with shifts from sAPPβ to sAPPα, from APL1β28 to 25, and from Aβ42 to 38 in all patients with iNPH. Our results suggest that Aβ production remained unchanged by the shunt procedure because the levels of sAPP and APL1β were unchanged. Moreover, the shift of Aβ from oligomer to monomer due to the shift of Aβ42 (easy to aggregate to Aβ38 (difficult to aggregate, and the improvement of interstitial-fluid flow, could lead to increased Aβ levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of Aβ in patients with iNPH.

  11. Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease: increased NPY levels and differential degradation of the NPY1-30 fragment.

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    Wagner, Leona; Björkqvist, Maria; Lundh, Sofia Hult; Wolf, Raik; Börgel, Arne; Schlenzig, Dagmar; Ludwig, Hans-Henning; Rahfeld, Jens-Ulrich; Leavitt, Blair; Demuth, Hans-Ulrich; Petersén, Åsa; von Hörsten, Stephan

    2016-06-01

    Huntington's disease (HD) is an inherited and fatal polyglutamine neurodegenerative disorder caused by an expansion of the CAG triplet repeat coding region within the HD gene. Progressive dysfunction and loss of striatal GABAergic medium spiny neurons (MSNs) may account for some of the characteristic symptoms in HD patients. Interestingly, in HD, MSNs expressing neuropeptide Y (NPY) are spared and their numbers is even up-regulated in HD patients. Consistent with this, we report here on increased immuno-linked NPY (IL-NPY) levels in human cerebrospinal fluid (hCSF) from HD patients (Control n = 10; early HD n = 9; mid HD n = 11). As this antibody-based detection of NPY may provide false positive differences as a result of the antibody-based detections of only fragments of NPY, the initial finding was validated by investigating the proteolytic stability of NPY in hCSF using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and selective inhibitors. A comparison between resulting NPY-fragments and detailed epitope analysis verified significant differences in IL-NPY1-36/3-36 and NPY1-30 levels between HD patients and control subjects with no significant differences between early vs mid HD cases. Ex vivo degradomics analysis demonstrated that NPY is initially degraded to NPY1-30 by cathepsin D in both HD patients and control subjects. Yet, NPY1-30 is then further differentially hydrolyzed by thimet oligopeptidase (TOP) in HD patients and by neprilysin (NEP) in control subjects. Furthermore, altered hCSF TOP-inhibitor Dynorphin A1-13 (Dyn-A1-13 ) and TOP-substrate Dyn-A1-8 levels indicate an impaired Dyn-A-TOP network in HD patients. Thus, we conclude that elevated IL-NPY-levels in conjunction with TOP-/NEP-activity/protein as well as Dyn-A1-13 -peptide levels may serve as a potential biomarker in human CSF of HD. Huntington's disease (HD) patients' cerebrospinal fluid (CSF) exhibits higher neuropeptide Y (NPY) levels. Further

  12. Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus

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    Miller Janet M

    2007-06-01

    Full Text Available Abstract Background Reactive gliosis has the potential to alter biomechanical properties of the brain, impede neuronal regeneration and affect plasticity. Determining the onset and progression of reactive astrogliosis and microgliosis due to hydrocephalus is important for designing better clinical treatments. Methods Reactive astrogliosis and microgliosis were evaluated as the severity of hydrocephalus increased with age in hydrocephalic H-Tx rats and control littermates. Previous studies have suggested that gliosis may persist after short-term drainage (shunt treatment of the cerebrospinal fluid. Therefore shunts were placed in 15d hydrocephalic rats that were sacrificed after 6d (21d of age or after 21d (36d of age. Tissue was processed for Western blot procedures and immunohistochemistry, and probed for the astrocytic protein, Glial Fibrillary Acidic Protein (GFAP and for microglial protein, Isolectin B4 (ILB4. Results In the parietal cortex of untreated hydrocephalic animals, GFAP levels increased significantly at 5d and at 12d compared to age-matched control rats. There was a continued increase in GFAP levels over control at 21d and at 36d. Shunting prevented some of the increase in GFAP levels in the parietal cortex. In the occipital cortex of untreated hydrocephalic animals, there was a significant increase over control in levels of GFAP at 5d. This trend continued in the 12d animals, although not significantly. Significant increases in GFAP levels were present in 21d and in 36d animals. Shunting significantly reduced GFAP levels in the 36d shunted group. Quantitative grading of immuno-stained sections showed similar changes in GFAP stained astrocytes. Immuno-stained microglia were altered in shape in hydrocephalic animals. At 5d and 12d, they appeared to be developmentally delayed with a lack of processes. Older 21d and 36d hydrocephalic animals exhibited the characteristics of activated microglia, with thicker processes and enlarged

  13. Predictive role of cerebrospinal fluid hydrogen sulfide in central nervous system leukemia

    Institute of Scientific and Technical Information of China (English)

    DU Shu-xu; XIAO Jiang; GUAN Feng; SUN Li-ming; WU Wan-shui; TANG Hong; DU Jun-bao; TANG Chao-shu; JIN Hong-fang

    2011-01-01

    Background Central nervous system leukemia (CNSL) is an important relapse in children with acute lymphoblastic leukemia (ALL).We investigated the possible role of endogenous hydrogen sulfide (H2S) of cerebrospinal fluid (CSF) in predicting CNSL.Methods From August 2008 to December 2010,380 children were enrolled in this study at Shijitan Hospital,China.These children were from 2 to 16 years old,and the median age was 6.5 years.They were divided into a CNSL group (7 cases),a leukemia group (307 cases),a non-leukemia group (26 cases) and a healthy group (40 children).CSF specimens were obtained from conventional lumbar punctured,then centrifuged and supernatants preserved for H2Sdetection.Leukemic cells precipitates from CSF were found in three cases,the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR),and H2S levels in serum were also measured.The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the predictive diagnosis role of CSF H2S in children with ALL and CNSL.Results The serum H2S contents of the CNSL and leukemia groups were (96.98+15.77) μmol/L and (93.35+17.16)μmol/L respectively,much higher than those of healthy,(44.29+2.15) μmol/L,and non-leukemia,(46.32±6.54) μmol/L,groups (P <0.01).Compared with the leukemia group,CSF H2S content of the CNSL group was significantly high (P <0.01).Meanwhile,in contrast to the non-leukemia group,CSF H2S contents of the CNSL and leukemia groups were both significantly increased (P <0.01).In addition,leukemic cells from CSF precipitations could express CBS and CSE mRNA.Furthermore,the ROC analysis showed the UAC was 0.929 (95% Cl:0.857-1.000),and the optimum cut-off value of CSF H2S was 12.08μmol/L,and the sensitivity and specificity were 83.3% and 97.2% respectively.Conclusions CSF H2S contents were significantly increased in children with CNSL.After treatment,H2S contents were decreased subsequently

  14. Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of dairy cows.

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    Laeger, T; Görs, S; Metges, C C; Kuhla, B

    2012-03-01

    Endocrines and metabolites in the circulation act as long-term hunger or satiety signals in the brain during negative energy balance and play an important role in the control of feed intake. These signals also occur in the cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem: 2 major centers of feed intake regulation. Thus CSF functions as a transport medium for fuel signals between blood and brain. The CSF metabolite concentrations are mainly under control of the blood-brain barriers, which provide specific carrier molecules facilitating the entry of substances required by the brain and protect the brain from factors that could impair neuronal function. The transport of small molecules such as amino acids (AA) across the blood-brain barriers may be limited by competing AA that share a common transporter for the uptake into brain. Consequently, CSF metabolite concentrations differ from those in blood. Thus it appears likely that central (CSF) rather than peripheral (blood) metabolites act as pivotal signals for the control of feed intake. However, the contribution of putative orexigenic and anorexigenic signals in CSF of cows has not been studied so far. Therefore, the aim of this study was to elucidate associations existing between both plasma and CSF metabolites, each in response to feed restriction-induced negative energy balance. Seven German Holstein dairy cows, between 87 and 96 DIM of the second lactation (milk yield, 27.9 L/d) were fed ad libitum (AL) for 4 d and CSF from the spinal cord and blood from the jugular vein was withdrawn before morning feeding at the fifth day. Subsequently, animals were feed restricted (R) to 50% of the previous AL intake for 4 d and CSF and plasma were collected at the ninth day. Body weight, feed intake, water intake, and milk production were determined. Thirty-one AA, β-hydroxybutyric acid, cholesterol, glucose, lactate, nonesterified fatty acids, urea, and osmolality were measured in both CSF and

  15. Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance

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    Andersson Kennet

    2011-03-01

    Full Text Available Abstract Background A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout or its reciprocal the outflow resistance (Rout, with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Prhad on the results. Methods Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3 ± 10.8 years (mean ± SD. The analysis was performed without (Cexcl Pr and with (Cincl Pr Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p Results Mean Cout for the 63 patients was: Cexcl Pr = 7.0 ± 4.0 (mean ± SD μl/(s kPa and Cincl Pr = 9.1 ± 4.3 μl/(s kPa and Rout was 19.0 ± 9.2 and 17.7 ± 11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r = 0.79, n = 63, p Cout= -2.1 ± 2.7 μl/(s kPa between methods was significant (p Rout was 1.2 ± 8.8 mmHg/ml/min. The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between ΔCout and Cout. Conclusions The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout

  16. Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    YUAN Zhi-hua; ZHU Jian-yong; HUANG Wei-dong; JIANG Jiu-kun; LU Yuan-qiang; XU Miao; SU Wei; JIANG Ting-ying

    2010-01-01

    Objective:To investigate the changes and effects of arginine vasopressin(AVP)in patients with acute traumatic subarachnoid hemorrhage(tSAH).Methods:The plasma and cerebrospinal fluid(CSF)level of AVP,and intracraniai pressure(ICP)were measured in a total of 21 patients within 24 hours after tSAH.The neurological status of the patients was evaluated by Glasgow Coma Scale(GCS).Correlation between AVP and ICP,CrCS was analyzed respectively.Meanwhile,18 healthy volunteers were recruited as control group.Results:Compared with control group,the levels(pg/ml)of AVP in plasma and CSF((x)±s)in tSAH group were significantly increased within 24 hours(38.72±24.71 vs 4.54±1.38and 34.61±21.43 vs 4.13±1.26,P<0.01),and was remarkably higher in GCS≤8 group than GCS>8 group(50.96±36.81 vs 25.26±12.87 and 44.68±31.72 vs 23.53±10.94,P<0.05).The CSF AVP level was correlated with ICP(r= 0.46,P<0.05),but no statistically significant correlation was found between plasma AVP,CSF AVP and initial GCS(r=-0.29,P>0.05 and r=-0.32,P>0.05,respectively).The ICP(mm Hg)in tSAH patients was elevated and higher in GCS≤8 group than in GCS>8 group(25.9±9.7 vs 17.6±5.2,P<0.05=.Conclusion:Our research suggests that AVP is correlated with the severity of tSAH,and may be involved in the pathophysiological process of brain damage in the early stage after tSAH.It seems that compared with the plasma AVP concentration,CSF AVP is more related to the severity of tSAH.

  17. Turnover rate of cerebrospinal fluid in female sheep: changes related to different light-dark cycles

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    Malpaux Benoit

    2009-08-01

    Full Text Available Abstract Background Sheep are seasonal breeders. The key factor governing seasonal changes in the reproductive activity of the ewe is increased negative feedback of estradiol at the level of the hypothalamus under long-day conditions. It has previously been demonstrated that when gonadotropin secretions are inhibited during long days, there is a higher concentration of estradiol in the cerebrospinal fluid (CSF than during short days. This suggests an involvement of the CSF and choroid plexus in the neuroendocrine regulatory loop, but the mechanisms underlying this phenomenon remain unknown. One possible explanation of this difference in hormonal content is an effect of concentration or dilution caused by variations in CSF secretion rate. The aim of this study was thus to investigate changes in the CSF turnover rate related to light-dark cycles. Methods The turnover rate of the CSF was estimated by measuring the time taken for the recovery of intraventricular pressure (IVP after removal of a moderate volume (0.5 to 2 ml of CSF (slope in mmHg/min. The turnover rate was estimated three times in the same group of sheep: during a natural period of decreasing day-length corresponding to the initial period when gonadotropin activity is stimulated (SG1, during a long-day inhibitory period (IG, and finally during a short-day stimulatory period (SG2. Results The time taken and the speed of recovery of initial IVP differed between groups: 8 min 30 sec, 0.63 ± 0.07 mmHg/min(SG1, 11 min 1 sec, 0.38 ± 0.06 mmHg/min (IG and 9 min 0 sec, 0.72 ± 0.15 mmHg/min (SG2. Time changes of IVP differed between groups (ANOVA, p p p = 0.41, but was significantly different from IG: 71.33 ± 16.59 μl/min (p = 0.016. Conclusion This study shows that the turnover rate of CSF in ewes changes according to the light-dark cycle; it is increased during short day periods and reduced in long day periods. This phenomenon could account for differences in hormonal concentrations in

  18. Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

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    Satoshi Yoshimura

    Full Text Available BACKGROUND: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF oligoclonal IgG bands (OBs and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. METHODOLOGY: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA, and varicella zoster virus (VZV in 94 patients with MS and 367 unrelated healthy controls (HCs. We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658. PRINCIPAL FINDINGS: CSF IgG abnormality was found in 59 of 94 (62.8% MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1 1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1 0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. CONCLUSIONS: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1 1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1 0405 and H. pylori infection are positively and negatively

  19. Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection

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    Bremell Daniel

    2013-01-01

    Full Text Available Abstract Background It has been suggested that cerebrospinal fluid (CSF CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB, as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited. Methods We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease. Results In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL, with a median concentration of 500 pg/mL (range 34–11,678. Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498. There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL. Conclusions We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.

  20. Early transient accumulation of methotrexate in the cerebrospinal fluid of rabbits after treatment with methotrexate and roentgen rays

    International Nuclear Information System (INIS)

    Concomitant application of intrathecal methotrexate (MTX) and cranial irradiation has been described as being able to cause brain abnormalities in patients with leukemia. In the investigation presented, rabbits were treated once weekly for 6 weeks with intraventricular MTX and irradiation. Cerebrospinal fluid (CSF) sampled at various time points after each treatment contained for the samples obtained 4 hours after treatment increasing amounts of MTX. This indicated a retardation in MTX clearance from the CSF. Such a retardation might contribute to the generation of brain abnormalities, although no data have as yet been obtained to prove this suggestion. (Auth.)

  1. Neuron-specific Enclose and Myelin Basic Protein in Cerebrospinal Fluid of Patients with First Episode Schizophrenia

    Institute of Scientific and Technical Information of China (English)

    LI Shuying; WU Hanrong; GUO Huirong; ZHAO Zheng

    2006-01-01

    In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P<0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P<0.05). These findings suggested that patients with schizophrenia had cerebral injury.

  2. Post-traumatic cerebrospinal fluid fistula: a case report; Fistula liquorica pos-traumatica - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Tamburus, Wander Miguel; Figueiredo Wanderley, Eliana Christina; Maciel, Damacio Ramon Kaimen; Narciso, Avelino Jose Soares; Sendenski, Mauricio Michalak [Universidade Estadual de Londrina, PR (Brazil). Centro de Ciencias da Saude

    1996-10-01

    Fronto-basal fracture occurs in around 5% of cranioencephalic trauma. the involved structures are: arachnoid, dura-mater, osseous base and the mucosa, and there us contact between the brain and the environment. Even with rupture of all these structures cerebrospinal fluid leakage may not occur; regardless of this, there may be infectious complications, such as bacterial meningitis or brain abscess. the authors report the case of a patient with head injury and four bacterial meningitis, the diagnosis of post-traumatic liquoric fistula being made only through magnetic resonance imaging. (author) 10 refs., 1 fig.

  3. Variations in the FRA10AC1 Fragile Site and 15q21 Are Associated with Cerebrospinal Fluid Aβ1-42 Level.

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    Qingqin S Li

    Full Text Available Proteolytic fragments of amyloid and post-translational modification of tau species in Cerebrospinal fluid (CSF as well as cerebral amyloid deposition are important biomarkers for Alzheimer's Disease. We conducted genome-wide association study to identify genetic factors influencing CSF biomarker level, cerebral amyloid deposition, and disease progression. The genome-wide association study was performed via a meta-analysis of two non-overlapping discovery sample sets to identify genetic variants other than APOE ε4 predictive of the CSF biomarker level (Aβ1-42, t-Tau, p-Tau181P, t-Tau:Aβ1-42 ratio, and p-Tau181P:Aβ1-42 ratio in patients enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI study. Loci passing a genome-wide significance threshold of P < 5 x 10-8 were followed-up for replication in an independent sample set. We also performed joint meta-analysis of both discovery sample sets together with the replication sample set. In the discovery phase, we identified variants in FRA10AC1 associated with CSF Aβ1-42 level passing the genome-wide significance threshold (directly genotyped SNV rs10509663 PFE = 1.1 x 10-9, imputed SNV rs116953792 PFE = 3.5 x 10-10, rs116953792 (Pone-sided = 0.04 achieved replication. This association became stronger in the joint meta-analysis (directly genotyped SNV rs10509663 PFE = 1.7 x 10-9, imputed SNV rs116953792 PFE = 7.6 x 10-11. Additionally, we identified locus 15q21 (imputed SNV rs1503351 PFE = 4.0 x 10-8 associated with CSF Aβ1-42 level. No other variants passed the genome-wide significance threshold for other CSF biomarkers in either the discovery sample sets or joint analysis. Gene set enrichment analyses suggested that targeted genes mediated by miR-33, miR-146, and miR-193 were enriched in various GWAS analyses. This finding is particularly important because CSF biomarkers confer disease susceptibility and may be predictive of the likelihood of disease progression in Alzheimer

  4. Hydration biomarkers and dietary fluid consumption of women.

    Science.gov (United States)

    Armstrong, Lawrence E; Johnson, Evan C; Munoz, Colleen X; Swokla, Brittany; Le Bellego, Laurent; Jimenez, Liliana; Casa, Douglas J; Maresh, Carl M

    2012-07-01

    Normative values and confidence intervals for the hydration indices of women do not exist. Also, few publications have precisely described the fluid types and volumes that women consume. This investigation computed seven numerical reference categories for widely used hydration biomarkers (eg, serum and urine osmolality) and the dietary fluid preferences of self-reported healthy, active women. Participants (n=32; age 20±1 years; body mass 59.6±8.5 kg; body mass index [calculated as kg/m(2)] 21.1±2.4) were counseled in the methods to record daily food and fluid intake on 2 consecutive days. To reduce day-to-day body water fluctuations, participants were tested only during the placebo phase of the oral contraceptive pill pack. Euhydration was represented by the following ranges: serum osmolality=293 to 294 mOsm/kg; mean 24-hour total fluid intake=2,109 to 2,506 mL/24 hours; mean 24-hour total beverage intake=1,300 to 1,831 mL/24 hours; urine volume=951 to 1,239 mL/24 hours; urine specific gravity=1.016 to 1.020; urine osmolality=549 to 705 mOsm/kg; and urine color=5. However, only 3% of women experienced a urine specific gravity hyperhydration, euhydration, and dehydration that can be used by registered dietitians and clinicians to counsel women about their hydration status. PMID:22889635

  5. Tumor interstitial fluid - a treasure trove of cancer biomarkers.

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    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J; Timmermans-Wielenga, Vera; Talman, Mai-Lis; Serizawa, Reza R; Moreira, José M A

    2013-11-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secretion, non-classical secretion, secretion via exosomes and membrane protein shedding. Consequently, the interstitial aqueous phase of solid tumors is a highly promising resource for the discovery of molecules associated with pathological changes in tissues. Firstly, it allows one to delve deeper into the regulatory mechanisms and functions of secretion-related processes in tumor development. Secondly, the anomalous secretion of molecules that is innate to tumors and the tumor microenvironment, being associated with cancer progression, offers a valuable source for biomarker discovery and possible targets for therapeutic intervention. Here we provide an overview of the features of tumor-associated interstitial fluids, based on recent and updated information obtained mainly from our studies of breast cancer. Data from the study of interstitial fluids recovered from several other types of cancer are also discussed. This article is a part of a Special Issue entitled: The Updated Secretome. PMID:23416532

  6. Effect of Head Position on Cerebrospinal Fluid Pressure in Cats: Comparison with Artificial Model

    Science.gov (United States)

    Klarica, Marijan; Radoš, Milan; Draganić, Pero; Erceg, Gorislav; Orešković, Darko; Maraković, Jurica; Bulat, Marin

    2006-01-01

    Aim To demonstrate that changes in the cerebrospinal fluid (CSF) pressure in the cranial cavity and spinal canal after head elevation from the horizontal level occur primarily due to the biophysical characteristics of the CSF system, ie, distensibility of the spinal dura. Methods Experiments in vivo were performed on cats and a new artificial model of the CSF system with dimensions similar to the CSF system in cats, consisting of non-distensible cranial and distensible spinal part. Measurements of the CSF pressure in the cranial and spinal spaces were performed in chloralose-anesthetized cats (n = 10) in the horizontal position on the base of a stereotaxic apparatus (reference zero point) and in the position in which the head was elevated to 5 cm and 10 cm above that horizontal position. Changes in the CSF pressure in the cranial and spinal part of the model were measured in the cranial part positioned in the same way as the head in cats (n = 5). Results When the cat was in the horizontal position, the values of the CSF pressure in the cranial (11.9 ± 1.1 cm H2O) and spinal (11.8 ± 0.6 cm H2O) space were not significantly different. When the head was elevated 5 cm or 10 cm above the reference zero point, the CSF pressure in the cranium significantly decreased to 7.7 ± 0.6 cm H2O and 4.7 ± 0.7 cm H2O, respectively, while the CSF pressure in the spinal space significantly increased to 13.8 ± 0.7 cm H2O and 18.5 ± 1.6 cm H2O, respectively (P<0.001 for both). When the artificial CSF model was positioned in the horizontal level and its cranial part elevated by 5 cm and 10 cm, the changes in the pressure were the same as those in the cats when in the same hydrostatic position. Conclusions The new model of the CSF system used in our study faithfully mimicked the changes in the CSF pressure in cats during head elevation in relation to the body. Changes in the pressure in the model were not accompanied by the changes in fluid volume in

  7. LYMPHOCYTE SUBSETS AND CYTOKINES IN BLOOD AND CEREBROSPINAL FLUID IN CHILDREN WITH VIRAL AND BACTERIAL MENINGITIS

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    L. A. Alekseeva

    2016-01-01

    an expressed system response of IL-8 and IL-10. Liquor T-lymphocyte content was relatively correlated with blood indicators whereas the fraction of NK exceeded it, and B-lymphocyte content was 3–4 times higher than in patients with viral meningitis. There was IL-6, IL-10, IFNγ and IL-4 response intrathecally, and 10-multiply-growth of IgG level. Thus, the redistribution of lymphocyte subpopulations, and system and local cytokine response in children with meningitis have both common and special features depending on the aetiology and severity of disease. Phenotyping of lymphocytes and determination of both cytokines and immunoglobulins simultaneously in two biologic fluid allow to clear up the pathogenetic value of immunologic abnormalities in blood and cerebrospinal fluid of the patients in the aspect of interactions between cell and humoral factors of system and local immune response in neuroinfections of various aetiology.

  8. Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion

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    Anna Junttila

    2016-04-01

    Full Text Available Background: TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD and amyotrophic lateral sclerosis (ALS patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables. Methods: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69 and ALS (n = 21 patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, Aβ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. Results: There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort. Conclusion: CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.

  9. Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST3.

    Science.gov (United States)

    Yamamoto-Watanabe, Yukiko; Watanabe, Mitsunori; Jackson, Mandy; Akimoto, Hiroyuki; Sugimoto, Kazuhiro; Yasujima, Minoru; Wakasaya, Yasuhito; Matsubara, Etsuro; Kawarabayashi, Takeshi; Harigaya, Yasuo; Lyndon, Alastair R; Shoji, Mikio

    2010-11-18

    Cystatin C (CC) is a cysteine protease inhibitor abundantly expressed in the central nervous system. Bunina bodies, small eosinophilic intraneuronal inclusions, are stain positive for CC and are the most specific histological hallmark of amyotrophic lateral sclerosis (ALS). In this study, employing a latex turbidimetric immunoassay, levels of CC in cerebrospinal fluid (CSF) were quantified in 130 age-matched individuals with either a neurological disorder [ALS, Alzheimer's disease (AD), Parkinson's disease (PD), tauopathy (TP), multiple system atrophy (MSA), chronic inflammatory demyelinating polyneuropathy (CIDP)] or no known neurological condition (normal control, NC). The CC level in CSF was found to be correlated with the age during the investigation but not the protein concentration. There was no difference in CC levels between NC and ALS or CIDP cases, whereas CC levels were significantly lower in MSA compared with NC. Of the 130 cases, 96 were genotyped, and G/A or A/A polymorphism at +73 within the CST3 gene was found in 28 individuals. The CC level was significantly lower in the combined group of G/A and A/A genotypes compared with G/G. The present data demonstrate that the level of CC in CSF should not be considered as a biomarker of ALS, but there is a correlation between CC levels and the CST3 genotype.

  10. Diagnostic values of cerebrospinal fluid t-tau and Aβ42 using Meso Scale Discovery assays for Alzheimer’s disease

    Science.gov (United States)

    Pan, Catherine; Korff, Ané; Galasko, Douglas; Ginghina, Carmen; Peskind, Elaine; Li, Ge; Quinn, Joseph; Montine, Thomas J.; Cain, Kevin; Shi, Min; Zhang, Jing

    2015-01-01

    Background Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid beta 1–42 peptide (Aβ42) that can aid in the diagnosis of Alzheimer’s disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis. Objective To validate the analytical and clinical performance of the MSD t-tau and Aβ42 kits and propose diagnostic cut-off values for the field. Methods The analytical performance of the CSF t-tau and Aβ42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, Aβ42 and t-tau/Aβ42 in three clinically characterized cohorts. Results Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/Aβ42 performed the best. Conclusions Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and Aβ42 assays. Based on a large, multi-center, clinically diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, Aβ42 and t-tau/Aβ42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories. PMID:25613100

  11. Validation of a Commercial Chemiluminescence Immunoassay for the Simultaneous Measurement of Three Different Amyloid-β Peptides in Human Cerebrospinal Fluid and Application to a Clinical Cohort.

    Science.gov (United States)

    Klafki, Hans-W; Hafermann, Henning; Bauer, Chris; Haussmann, Ute; Kraus, Inga; Schuchhardt, Johannes; Muck, Stephan; Scherbaum, Norbert; Wiltfang, Jens

    2016-09-01

    A comprehensive assay validation campaign of a commercially available chemiluminescence multiplex immunoassay for the simultaneous measurement of the amyloid-β peptides Aβ38, Aβ40, and Aβ42 in human cerebrospinal fluid (CSF) is presented. The assay quality parameters we addressed included impact of sample dilution, parallelism, lower limits of detection, lower limits of quantification, intra- and inter-assay repeatability, analytical spike recoveries, and between laboratory reproducibility of the measurements. The assay performed well in our hands and fulfilled a number of predefined acceptance criteria. The CSF levels of Aβ40 and Aβ42 determined in a clinical cohort (n = 203) were statistically significantly correlated with available ELISA data of Aβ1-40 (n = 158) and Aβ1-42 (n = 179) from a different laboratory. However, Bland-Altman method comparison indicated systematic differences between the assays. The data presented here furthermore indicate that the CSF concentration of Aβ40 can surrogate total CSF Aβ and support the hypothesis that the Aβ42/Aβ40 ratio outperforms CSF Aβ42 alone as a biomarker for Alzheimer's disease due to a normalization to total Aβ levels. PMID:27567847

  12. [A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

    Science.gov (United States)

    Arita, Yuki; Tono, Toshihiro; Hosoda, Tomohiro; Taguchi, Hiroaki; Sakamoto, Mitsuo; Osone, Yasuo; Nozaki, Hiroyuki

    2016-05-01

    We report a patient with leptospirosis caused by infection with Leptospira interrogans serovar Rachmati. A 30-year-old Japanese man took part in a survival camp on Iriomote Island, Okinawa, from July 9 to July 15, 2014. During the camp, he swam in the river and kayaked. He developed a high fever and fatigue 7 days after completing his trip and was admitted to our hospital on July 22. On admission, he complained of a posterior cervical pain and a loss of appetite. Laboratory findings revealed granulocytosis, mildly elevated AST and ALT levels, elevated BUN and Cr levels, and a significantly elevated CRP level. No pathogenic bacteria were isolated from blood, urine, or cerebrospinal fluid cultures. We included leptospirosis in the differential diagnosis because of the patient's history of participating in a survival camp on Iriomote Island. Minocycline 200 mg, p.o. showed an excellent efficacy. The Leptospira flagellar gene FlaB was detected using a cerebrospinal fluid PCR. A microscopic agglutination test (MAT) during the convalescent stage demonstrated significant increases in antibodies against L. interrogans serovar Rachmati, confirming the diagnosis of leptospirosis. A medical history including occupation and recent travel history, and an adequate specimen sampling are crucial for the accurate and early diagnosis of leptospirosis. PMID:27529969

  13. Cerebrospinal fluid rhinorrhea as a complication of ACTH-secreting pituitary macroadenoma in a patient with morbid obesity

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    Dar'ya Viktorovna Petrova

    2014-11-01

    Full Text Available Cushing's disease (CD is a progressive neuroendocrine disease caused by a pituitary tumor producing excessive amounts of ACTH. In most cases (80-85% the cause of the disease is a pituitary corticotroph microadenomas (located within the sella, measuring 3–10 mm, rarely multiple microadenomas and only 15% of cases are presented as corticotroph hyperplasia or pituitary macroadenoma extending beyond the sella. The macroadenomas in CD usually extend suprasellar (10%, infrasellar tumor growth is relatively rare (5%. If the clinical picture is subtle, the symptoms are caused by the development "mass effect" of the tumor as it propagates to the surrounding pituitary structures. Suprasellar growth leads to compression of the optic chiasm with narrowing of visual fields, infrasellar growth destructs the bottom of the sella turcica and may cause nasal cerebrospinal fluid leak, which is dangerous due depressurization of the cranial cavity and its communication with environmental pathogens, development of life-threatening conditions such as meningitis, meningoencephalitis, ventriculitis. Leading life-threatening complications of the CD are infectious and cardiovascular. But in the case of nasal liquorrhea with expansion of the tumor in sphenoid sinus with destruction of the bottom of the sella, there is an immediate threat to the life of the patient. This article presents an example of a patient with morbid obesity and lack of specific clinical manifestations of CD, in whom the diagnosis of disease CD was made on the results of laboratory and instrumental examination, which experienced a spontaneous nasal cerebrospinal fluid leak.

  14. Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis mimicking dengue encephalitis in a child

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    Indrajit Suresh

    2015-09-01

    Full Text Available The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL has been infrequently reported in children. This condition can mimic many serious conditions of the central nervous system, while actually being benign in nature. The authors present the report of an 8 year old developmentally normal female with family and personal history of migraine, which was initially suspected to have Dengue encephalitis. She had an episode of seizures, meningism and altered sensorium. Normal mental status and physical findings were observed intermittently. Detailed evaluation including analysis of blood, cerebrospinal fluid (CSF and neuroimaging were done. Neuro-infections, vascular pathology and autoimmune disorders were ruled out prior to reaching a diagnosis of HaNDL. She responded well to symptomatic treatment and made a full recovery. She was discharged on migraine prophylaxis considering her history. Dengue as causation and the occurrence of seizures in HaNDL has not been reported previously. [Int J Res Med Sci 2015; 3(9.000: 2481-2484

  15. Functional analysis of Pro-inflammatory properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro

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    Schneider Ulf C

    2012-02-01

    Full Text Available Abstract Background To functionally characterize pro-inflammatory and vasoconstrictive properties of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage (SAH in vivo and in vitro. Methods The cerebrospinal fluid (CSF of 10 patients suffering from SAH was applied to the transparent skinfold chamber model in male NMRI mice which allows for in vivo analysis of the microcirculatory response to a superfusat. Microvascular diameter changes were quantified and the numbers of rolling and sticking leukocytes were documented using intravital multifluorescence imaging techniques. Furthermore, the pro-inflammatory properties of CSF were assessed in vitro using a monocyte transendothelial migration assay. Results CSF superfusion started to induce significant vasoconstriction on days 4 and 6 after SAH. In parallel, CSF superfusion induced a microvascular leukocyte recruitment, with a significant number of leukocytes rolling (day 6 and sticking (days 2-4 to the endothelium. CSF of patients presenting with cerebral edema induced breakdown of blood vessel integrity in our assay as evidenced by fluorescent marker extravasation. In accordance with leukocyte activation in vivo, significantly higher in vitro monocyte migration rates were found after SAH. Conclusion We functionally characterized inflammatory and vasoactive properties of patients' CSF after SAH in vivo and in vitro. This pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of early and delayed brain injury as well as vasospasm development following SAH.

  16. [A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

    Science.gov (United States)

    Arita, Yuki; Tono, Toshihiro; Hosoda, Tomohiro; Taguchi, Hiroaki; Sakamoto, Mitsuo; Osone, Yasuo; Nozaki, Hiroyuki

    2016-05-01

    We report a patient with leptospirosis caused by infection with Leptospira interrogans serovar Rachmati. A 30-year-old Japanese man took part in a survival camp on Iriomote Island, Okinawa, from July 9 to July 15, 2014. During the camp, he swam in the river and kayaked. He developed a high fever and fatigue 7 days after completing his trip and was admitted to our hospital on July 22. On admission, he complained of a posterior cervical pain and a loss of appetite. Laboratory findings revealed granulocytosis, mildly elevated AST and ALT levels, elevated BUN and Cr levels, and a significantly elevated CRP level. No pathogenic bacteria were isolated from blood, urine, or cerebrospinal fluid cultures. We included leptospirosis in the differential diagnosis because of the patient's history of participating in a survival camp on Iriomote Island. Minocycline 200 mg, p.o. showed an excellent efficacy. The Leptospira flagellar gene FlaB was detected using a cerebrospinal fluid PCR. A microscopic agglutination test (MAT) during the convalescent stage demonstrated significant increases in antibodies against L. interrogans serovar Rachmati, confirming the diagnosis of leptospirosis. A medical history including occupation and recent travel history, and an adequate specimen sampling are crucial for the accurate and early diagnosis of leptospirosis.

  17. Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study.

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    Hashimoto, K; Bruno, D; Nierenberg, J; Marmar, C R; Zetterberg, H; Blennow, K; Pomara, N

    2016-03-01

    Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N=28; age- and gender-matched comparison group, N=19) at baseline and 3-year follow-up (MDD group, N=19; comparison group, N=17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by high-performance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.

  18. Brain MRI in patients with multiple sclerosis with oligoclonal cerebrospinal fluid bands

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    Mesaroš Šarlota

    2003-01-01

    Full Text Available Locally produced oligoclonal IgG bands (OCB are present in the cerebrospinal fluid (CSF of 95% patients with multiple sclerosis (MS[2,3]. The most sensitive method for the detection of OCB is isoelectric focusing (IEF [1]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [2,9]. This study was designed to compare brain magnetic resonance imagining (MRI findings between CSF OCB positive and negative MS patients. The study comprised 22 OB negative patients with clinically definite MS and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In the both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS score. T2 weighted MRI of the brain was performed on a Siemens Magnetom (1.0 T. Lesions were countred and sized for 15 anatomically defined locations:7 periventricular (PV and 8 non-periventricular (NPV regions. An arbitrary scoring system weighted for lesions size was used to estimate total and regional lesions loads: a1 point was given for each lesion with a diameter 1-5 mm, b 2 points for one lesion with a diameter 6-10 mm, c 3 points for one over 10 mm, and confluent lesions scored one extra point [16]. Atrophy were scored as follows: 0-normal size, 1-mild atrophy, 2-moderate atrophy and 3-severe atrophy. Mean score of total brain MRI loads was lower in OCB negative than in OCB positive MS patients (44 vs. 50 but the difference was not statistically significant. Mean periventricular (32 vs. 23 non-periventricular (26 vs. 19 and infratentorial (11 vs. 9 scores were higher in OCB positive MS group in comparison with OCB negative patients but non-significant (figure 1. There was no correlation between EDSS score and total MRI lesions load in OCB negative MS patients, while in OCB positive group we detected significant correlation between EDSS score and total MRI lesions load (p=0.026 (figure 2. The results of this study demonstrate that

  19. Evolutionary development of embryonic cerebrospinal fluid composition and regulation: an open research field with implications for brain development and function.

    Science.gov (United States)

    Bueno, David; Garcia-Fernàndez, Jordi

    2016-01-01

    Within the consolidated field of evolutionary development, there is emerging research on evolutionary aspects of central nervous system development and its implications for adult brain structure and function, including behaviour. The central nervous system is one of the most intriguing systems in complex metazoans, as it controls all body and mind functions. Its failure is responsible for a number of severe and largely incurable diseases, including neurological and neurodegenerative ones. Moreover, the evolution of the nervous system is thought to be a critical step in the adaptive radiation of vertebrates. Brain formation is initiated early during development. Most embryological, genetic and evolutionary studies have focused on brain neurogenesis and regionalisation, including the formation and function of organising centres, and the comparison of homolog gene expression and function among model organisms from different taxa. The architecture of the vertebrate brain primordium also reveals the existence of connected internal cavities, the cephalic vesicles, which in fetuses and adults become the ventricular system of the brain. During embryonic and fetal development, brain cavities and ventricles are filled with a complex, protein-rich fluid called cerebrospinal fluid (CSF). However, CSF has not been widely analysed from either an embryological or evolutionary perspective. Recently, it has been demonstrated in higher vertebrates that embryonic cerebrospinal fluid has key functions in delivering diffusible signals and nutrients to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. Moreover, it has been shown that the composition and homeostasis of CSF are tightly controlled in a time-dependent manner from the closure of the anterior neuropore, just before the initiation of primary neurogenesis, up to the formation of functional choroid plexuses. In

  20. Evolutionary development of embryonic cerebrospinal fluid composition and regulation: an open research field with implications for brain development and function.

    Science.gov (United States)

    Bueno, David; Garcia-Fernàndez, Jordi

    2016-03-15

    Within the consolidated field of evolutionary development, there is emerging research on evolutionary aspects of central nervous system development and its implications for adult brain structure and function, including behaviour. The central nervous system is one of the most intriguing systems in complex metazoans, as it controls all body and mind functions. Its failure is responsible for a number of severe and largely incurable diseases, including neurological and neurodegenerative ones. Moreover, the evolution of the nervous system is thought to be a critical step in the adaptive radiation of vertebrates. Brain formation is initiated early during development. Most embryological, genetic and evolutionary studies have focused on brain neurogenesis and regionalisation, including the formation and function of organising centres, and the comparison of homolog gene expression and function among model organisms from different taxa. The architecture of the vertebrate brain primordium also reveals the existence of connected internal cavities, the cephalic vesicles, which in fetuses and adults become the ventricular system of the brain. During embryonic and fetal development, brain cavities and ventricles are filled with a complex, protein-rich fluid called cerebrospinal fluid (CSF). However, CSF has not been widely analysed from either an embryological or evolutionary perspective. Recently, it has been demonstrated in higher vertebrates that embryonic cerebrospinal fluid has key functions in delivering diffusible signals and nutrients to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. Moreover, it has been shown that the composition and homeostasis of CSF are tightly controlled in a time-dependent manner from the closure of the anterior neuropore, just before the initiation of primary neurogenesis, up to the formation of functional choroid plexuses. In