Sample records for cerebrospinal fluid level

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

    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


    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 folate and cobalamin levels in febrile convulsion.

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


    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

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

    Erdal Taskın


    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.

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

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


    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

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

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


    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

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

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


    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...

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

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


    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

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

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


    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

  9. Evidence for Elevated Cerebrospinal Fluid ERK1/2 Levels in Alzheimer Dementia

    Philipp Spitzer


    Full Text Available Cerebrospinal fluid (CSF samples from 33 patients with Alzheimer dementia (AD, 21 patients with mild cognitive impairment who converted to AD during followup (MCI-AD, 25 patients with stable mild cognitive impairment (MCI-stable, and 16 nondemented subjects (ND were analyzed with a chemiluminescence immunoassay to assess the levels of the mitogen-activated protein kinase ERK1/2 (extracellular signal-regulated kinase 1/2. The results were evaluated in relation to total Tau (tTau, phosphorylated Tau (pTau, and beta-amyloid 42 peptide (Aβ42. CSF-ERK1/2 was significantly increased in the AD group as compared to stable MCI patients and the ND group. Western blot analysis of a pooled cerebrospinal fluid sample revealed that both isoforms, ERK1 and ERK2, and low amounts of doubly phosphorylated ERK2 were detectable. As a predictive diagnostic AD biomarker, CSF-ERK1/2 was inferior to tTau, pTau, and Aβ42.

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

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


    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

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

    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. 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.

    Takahashi, H


    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

  13. Cerebrospinal fluid endorphins in schizophrenia

    Opioid-receptor-active material, endorphins, has been measured in cerebrospinal fluid samples obtained from schizophrenics. A chromatographic procedure isolated the Fraction I endorphin which was quantitated in a receptorassay. At least two cerebrospinal fluid samples were obtained from each patient, at day 0 with no medication and at days 30 and 60 after medication with fluphenazine under standardized conditions. Three series of patients were included: acute schizophrenics (n=11); re-entry schizophrenics (n=7) who have previously been treated with neuroleptics but were readmitted to hospital usually as a consequence of stopped medication, and chronic schizophrenics (n=9) who had been without neuroleptics for at least 2 weeks prior to day 0. At day 0, 6/9 acute cases, 4/6 of re-entry and 2/9 chronic cases had endorphin levels above the range of healthy volunteers. The levels in chronic cases were significantly lower than those in acute cases. Treatment with neuroleptics significantly lowered the endorphin levels in acute cases. These results confirm and extend previous observations. (author)

  14. Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to onset.

    Kornum, Birgitte Rahbek; Pizza, Fabio; Knudsen, Stine; Plazzi, Giuseppe; Jennum, Poul; Mignot, Emmanuel


    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

  15. Diagnostic Value of Cerebrospinal Fluid Level of Carcinoembryonic Antigen in Patients with Leptomeningeal Carcinomatous Metastasis

    Kang, Sung Jin; Kim, Kwang Soo; Ha, Yoon Suk; Huh, So Young; Lee, Ji Hyun; Kim, Jong Kuk; Kim, Min Jeong


    Background and Purpose Multifocal seeding of the leptomeninges by malignant cells, which is usually referred to as leptomeningeal carcinomatous metastasis, produces substantial morbidity and mortality. The diagnosis of leptomeningeal metastasis is usually established by cerebrospinal fluid (CSF) investigation, including cytology, cell counts, protein, glucose, and a tumor marker such as carcinoembryonic antigen (CEA). This study examined the diagnostic value of CEA in the CSF. Methods We meas...

  16. Cerebrospinal Fluid Hypocretin-1 (Orexin-A) Level Fluctuates with Season and Correlates with Day Length.

    Boddum, Kim; Hansen, Mathias Hvidtfelt; Jennum, Poul Jørgen; Kornum, Birgitte Rahbek


    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. PMID:27008404

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

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


    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...... in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ(X-38), Aβ(X-40), and Aβ(X-42), with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15 μg/mL in the CSF and 1.20±1.88 μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ42...

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

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


    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

  19. Adhesion molecule levels in serum and cerebrospinal fluid in children with bacterial meningitis and sepsis

    Soad M Jaber


    Full Text Available Background : Adhesion molecules play a role in leukocyte recruitment during central nervous system (CNS inflammation. Aim: This study was designed to compare serum, cerebrospinal fluid (CSF concentrations of adhesion molecules in children with meningitis and sepsis, and to evaluate their sources. Setting : This study was carried out at Pediatric Department, King Abdulaziz University Hospital from January 2007 to June 2008. Design: Serum and CSF samples were collected on admission from meningitis (n = 40, sepsis (n = 20 patients, and sera from controls (n = 20. Materials and Methods : Endothelial (E, leukocyte (L, platelet (P selectins intercellular cell adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecules-1 (VCAM-1 were measured using ELISA. Statistics : ANOVA and Spearman′s correlations were used. Adhesion molecules with albumin concentration were estimated in CSF/serum to calculate concentration quotients. Results : In meningitis, serum sE-, sL-, sP-selectins sICAM-1, sVCAM-1 levels were higher than controls. Compared to sepsis, serum sE-selectin, sL-selectin, sVCAM-1, CSF-sL-selectin, CSF-sVCAM-1, VCAM-1 ratio and index were higher, while serum sP-selectin was lower than meningitis. sE-selectin ratio, CSF sICAM-1 were higher in meningitis with positive than negative culture. The sE-selectin index was higher in meningitis with neurological complication than those without it. In meningitis, correlation was found between CSF protein and CSF white blood cell counts (WBCs, CSF sICAM-1, CSF sVCAM-1 and between CSF sE-selectin and CSF sICAM-1. Conclusions : This study supports the role of adhesion molecules especially sL-selectin, sVCAM-1 in meningitis and suggests further research to determine their use as biomarkers for meningitis and use of their antagonists as therapeutic for CNS inflammation. The presence of discrepancy of CSF/serum ratios for molecules of same molecular weight suggest intrathecal shedding in addition to

  20. Protein profiling of cerebrospinal fluid

    Simonsen, Anja H


    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....

  1. Cerebrospinal Fluid Pressure and Glaucoma

    Jonas, Jost B; Ningli Wang


    Eyes with normal-pressure glaucoma and those with high-pressure glaucoma can show a similar optic nerve head appearance, while eyes with vascular optic neuropathies show a markedly different optic disc appearance. Factors in addition to intraocular pressure (IOP) may thus play a role in the pathogenesis of glaucomatous optic neuropathy. Clinical and experimental studies showed that (1) physiologic associations between cerebrospinal fluid (CSF) pressure, systemic arterial blood pressure, IOP a...

  2. Simulation of cerebrospinal fluid transport

    Otáhal, Jakub; Štěpáník, Z.; Kaczmarská, A.; Maršík, František; Brož, Z.; Otáhal, S.


    Roč. 38, 11-12 (2007), s. 802-809. ISSN 0965-9978 Grant ostatní: GA UK(CZ) 112/2005; GA UK(CZ) 114/2005; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z20760514 Keywords : cerebrospinal fluid * pulsation * mathematical modeling Subject RIV: BO - Biophysics Impact factor: 0.529, year: 2007

  3. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

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


    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...

  4. Intracranial flow of cerebrospinal fluid

    This paper reports cerebrospinal fluid (CSF) flow in the third ventricle, aqueduct, fourth ventricle, basal cisterns, and subarachnoid spaces at the cervical-medullary junction evaluated in 25 patients and 10 normal volunteers. Information was acquired on 1.5-T magnet with a cardiac-gated, single-section, gradient-echo technique and displayed via closed-loop cine imaging. Qualitative assessment of flow patterns via magnitude reconstruction was correlated with quantitative data generated via phase reconstruction. Normal patterns of CSF flow were established. Pathologic changes involving these pathways altered the flow patterns, either causing increased turbulence and flow of CSF or decreasing the expected flow

  5. Season of sampling and season of birth influence serotonin metabolite levels in human cerebrospinal fluid.

    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.

  6. Levels of alpha- and beta-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients

    Sennvik, K; Fastbom, J; Blomberg, M;


    Alternative cleavage of the amyloid precursor protein (APP) results in generation and secretion of both soluble APP (sAPP) and beta-amyloid (Abeta). Abeta is the main component of the amyloid depositions in the brains of Alzheimer's disease (AD) patients. Using Western blotting, we compared the...... levels of alpha-secretase cleaved sAPP, beta-secretase cleaved sAPP and total sAPP, in cerebrospinal fluid (CSF) from 13 sporadic AD patients and 13 healthy controls. Our findings show significant amounts of beta-secretase cleaved sAPP in CSF. There was no statistically significant difference in the...... levels of beta-secretase cleaved sAPP between AD patients and controls. The levels of alpha-secretase cleaved sAPP and total sAPP were, however, found to be significantly lower in the AD patients than in the controls....

  7. Cerebrospinal fluid levels of nitric oxide metabolites predict response to methylprednisolone treatment in multiple sclerosis and optic neuritis

    Sellebjerg, F; Giovannoni, G; Hand, A; Madsen, H.O.; Jensen, C.V.; Garred, P

    The role of nitric oxide (NO) in multiple sclerosis (MS) is not clear. We found increased cerebrospinal fluid concentrations of the NO degradation products nitrate (NO(x)) in clinically definite MS but not in clinically isolated syndromes. High CSF concentrations of NO(x) correlated with long att...

  8. Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis

    Kułakowska, Alina; Byfield, Fitzroy J; Żendzian-Piotrowska, Małgorzata; Zajkowska, Joanna M; Drozdowski, Wiesław; Mroczko, Barbara; Janmey, Paul A.; Bucki, Robert


    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...

  9. Evaluation of Magnesium Levels in Serum and Cerebrospinal Fluid of Patients with Febrile Convulsion Hospitalized in Bahrami Hospital in Tehran in 2010-2011

    Nahid Khosroshahi; Laleh Ghadirian; Kamyar Kamrani


    Evaluation of magnesium levels in serum and cerebrospinal fluid of patients with febrile convulsion (FC) hospitalized in Bahrami hospital in Tehran in 2010-2011. In the past, decreased levels of magnesium in serum and CSF of patients with FC were reported. The purpose of this study was to identify the possible role of magnesium in febrile seizures in children. Identifying this condition, we may control seizures and also prevent subsequent convulsion. In this cross-sectional study, inclusion c...

  10. Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes

    Wu, M.-F.; Nienhuis, R.; Maidment, N.; Lam, H.A.; Siegel, J. M.


    Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study, we have compared the effects of treadmill running to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level bey...

  11. Cerebrospinal Fluid Proteomics of Multiple Sclerosis Patients

    M.P. Stoop (Marcel)


    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

  12. The proteomic toolbox for studying cerebrospinal fluid

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


    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

  13. Relation between change in Ca and Mg levels of cerebrospinal fluid after subarachnoid hemorrhage and the occurrence of vasospasm

    Sato, N.; Kuroda, K.; Suzuki, M.; Ogawa, A. [Iwate Medical University, School of Medicine, Morioka, Iwate (Japan); Sera, K.


    Cerebral vasospasm is a characteristic complication after subarachnoid hemorrhage (SAH), and the onset of vasospasm is a very important factor to decide the patient's outcome. Though various casual factors have been proposed for cerebral vasospasm after SAH, none of them explain the whole pathomechanism of vasospasm. To evaluate the role of trace elements in vasospasm, we have examined the sequential change in element concentration in the cerebrospinal fluid (CSF) after SAH by PIXE, and have investigated the relation between trace elements and vasospasm. We obtained the CSF samples from cisternal drainage of 17 patients with SAH who underwent radical surgery within 48 hours from the onset. The drainage was placed into basal cisterns at the end of the operation. Three sampling times (3-5, 7-9 and 12-14 days from the onset) were scheduled, because vasospasm is likely to occur from day 4 through day 14 after the onset. Cerebral angiograms were performed to classify vasospasm on day 1 and 7 after the onset. We measured 29 elements in the CSF and focused on Ca and Mg levels in this study, since Ca-influx into the smooth muscle cells is a principal mechanism of muscle contraction, and the competition between Ca and Mg is closely related to the muscle contraction. We found a significantly lower levels of Mg in the CSF of patients with vasospasm on days 7-9 after the onset. These results suggest that Mg in the CSF possibly ameliorate vasoconstriction due to Ca in the pathomechanism of vasospasm. (author)

  14. Cerebrospinal fluid biomarker candidates for parkinsonian disorders



    Full Text Available The parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson's disease (PD and atypical parkinsonian disorders, such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in atypical parkinsonian disorders compared with PD and healthy controls. The new "omics" techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives.

  15. Characterization of individual mouse cerebrospinal fluid proteomes

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


    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.

  16. Substance P in human cerebrospinal fluid

    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)

  17. Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents.

    Carolina Lahmann

    Full Text Available Activating mutations in the Kir6.2 (KCNJ11 subunit of the ATP-sensitive potassium channel cause neonatal diabetes (ND. Patients with severe mutations also suffer from neurological complications. Glibenclamide blocks the open KATP channels and is the treatment of choice for ND. However, although glibenclamide successfully restores normoglycaemia, it has a far more limited effect on the neurological problems. To assess the extent to which glibenclamide crosses the blood-brain barrier (BBB in vivo, we quantified glibenclamide concentrations in plasma, cerebrospinal fluid (CSF, and brain tissue of rats, control mice, and mice expressing a human neonatal diabetes mutation (Kir6.2-V59M selectively in neurones (nV59M mice. As only small sample volumes can be obtained from rodents, we developed a highly sensitive method of analysis, using liquid chromatography tandem mass spectrometry acquisition with pseudo-selected reaction monitoring, achieving a quantification limit of 10ng/ml (20nM glibenclamide in a 30μl sample. Glibenclamide was not detectable in the CSF or brain of rats after implantation with subcutaneous glibenclamide pellets, despite high plasma concentrations. Further, one hour after a suprapharmacological glibenclamide dose was administered directly into the lateral ventricle of the brain, the plasma concentration was twice that of the CSF. This suggests the drug is rapidly exported from the CSF. Elacridar, an inhibitor of P-glycoprotein and breast cancer resistance protein (major multidrug resistance transporters at the BBB, did not affect glibenclamide levels in CSF and brain tissue. We also identified a reduced sensitivity to volatile anaesthetics in nV59M mice and showed this was not reversed by systemic delivery of glibenclamide. Our results therefore suggest that little glibenclamide reaches the central nervous system when given systemically, that glibenclamide is rapidly removed across the BBB when given intracranioventricularly

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

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


    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...

  19. Ongoing HIV replication in cerebrospinal fluid under successful monotherapy

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


    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

  20. Risk factors for suicide among patients with schizophrenia: a cohort study focused on cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid

    Neider, Daniel; Lindström, Leif H; Bodén, Robert


    Background The objective of this study was to investigate the association between 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF), bullying, and later suicide among patients with schizophrenia. Methods Ninety-nine patients with schizophrenia were included. Correlations of clinical factors, 5-HIAA and HVA, and later suicide were investigated. Results Twelve patients committed suicide (12%) during a 28-year follow-up period. Later suicide was correlated to bullying in childhood (P=0.02) and a lower quotient of HVA/5-HIAA in CSF (P<0.05). Conclusion Suicide in schizophrenia is related to childhood exposedness and CSF neurotransmitter levels. PMID:27468235

  1. Genome-wide association reveals genetic effects on human Aβ42 and τ protein levels in cerebrospinal fluids: a case control study

    Schellenberg Gerard D; Han Mi-Ryung; Wang Li-San


    Abstract Background Alzheimer's disease (AD) is common and highly heritable with many genes and gene variants associated with AD in one or more studies, including APOE ε2/ε3/ε4. However, the genetic backgrounds for normal cognition, mild cognitive impairment (MCI) and AD in terms of changes in cerebrospinal fluid (CSF) levels of Aβ1-42, T-tau, and P-tau181P, have not been clearly delineated. We carried out a genome-wide association study (GWAS) in order to better define the genetic background...

  2. Genome-wide association reveals genetic effects on human Aβ42 and τ protein levels in cerebrospinal fluids: a case control study

    Han, Mi-Ryung; Schellenberg, Gerard D.; Wang, Li-San


    Background Alzheimer's disease (AD) is common and highly heritable with many genes and gene variants associated with AD in one or more studies, including APOE ε2/ε3/ε4. However, the genetic backgrounds for normal cognition, mild cognitive impairment (MCI) and AD in terms of changes in cerebrospinal fluid (CSF) levels of Aβ1-42, T-tau, and P-tau181P, have not been clearly delineated. We carried out a genome-wide association study (GWAS) in order to better define the genetic backgrounds to thes...

  3. Evaluation of Magnesium Levels in Serum and Cerebrospinal Fluid of Patients with Febrile Convulsion Hospitalized in Bahrami Hospital in Tehran in 2010-2011

    Nahid Khosroshahi


    Full Text Available Evaluation of magnesium levels in serum and cerebrospinal fluid of patients with febrile convulsion (FC hospitalized in Bahrami hospital in Tehran in 2010-2011. In the past, decreased levels of magnesium in serum and CSF of patients with FC were reported. The purpose of this study was to identify the possible role of magnesium in febrile seizures in children. Identifying this condition, we may control seizures and also prevent subsequent convulsion. In this cross-sectional study, inclusion criteria were the existence of convulsion due to fever and exclusion criteria were having a known neurological disease which could induce a seizure, and children younger than one month. In each group (cases include children with febrile convulsion and controls include febrile children without convulsion, Mg was measured in blood, and cerebrospinal fluid of 90 children and then they were compared. The data were analyzed by SPSS (α=0.05. The mean serum and CSF levels of Mg in case and control groups were equal (P<0.87 and P<0.22 respectively. There was no difference between two groups in terms of sex, but mean age was significantly different (P<0.003. There was not an association between serum and CSF levels of magnesium and the presence of FC. Therefore, it’s not suggested to measure the level of magnesium in serum or CSF in children with fever routinely.

  4. Evaluation of Magnesium Levels in Serum and Cerebrospinal Fluid of Patients with Febrile Convulsion Hospitalized in Bahrami Hospital in Tehran in 2010-2011.

    Khosroshahi, Nahid; Ghadirian, Laleh; Kamrani, Kamyar


    Evaluation of magnesium levels in serum and cerebrospinal fluid of patients with febrile convulsion (FC) hospitalized in Bahrami hospital in Tehran in 2010-2011. In the past, decreased levels of magnesium in serum and CSF of patients with FC were reported. The purpose of this study was to identify the possible role of magnesium in febrile seizures in children. Identifying this condition, we may control seizures and also prevent subsequent convulsion. In this cross-sectional study, inclusion criteria were the existence of convulsion due to fever and exclusion criteria were having a known neurological disease which could induce a seizure, and children younger than one month. In each group (cases include children with febrile convulsion and controls include febrile children without convulsion), Mg was measured in blood, and cerebrospinal fluid of 90 children and then they were compared. The data were analyzed by SPSS (α=0.05). The mean serum and CSF levels of Mg in case and control groups were equal (P<0.87 and P<0.22 respectively). There was no difference between two groups in terms of sex, but mean age was significantly different (P<0.003). There was not an association between serum and CSF levels of magnesium and the presence of FC. Therefore, it's not suggested to measure the level of magnesium in serum or CSF in children with fever routinely. PMID:26749235


    Whedon, James M; Glassey, Donald


    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...

  6. Spectrophotometry for cerebrospinal fluid pigment analysis

    Petzold, A.; Sharpe, L. T.; Keir, G


    The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein, and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity an...

  7. Tick borne encephalitis without cerebrospinal fluid pleocytosis

    Stupica, Daša; Strle, Franc; Avšič-Županc, Tatjana; Logar, Mateja; Pečavar, Blaž; Bajrović, Fajko F.


    Background Tick borne encephalitis is the most frequent vector-transmitted infectious disease of the central nervous system in Europe and Asia. The disease caused by European subtype of tick borne encephalitis virus has typically a biphasic clinical course with the second phase presenting as meningitis, meningoencephalitis, or meningoencephalomyelitis. Cerebrospinal fluid pleocytosis is considered a condition sine qua non for the diagnosis of neurologic involvement in tick borne encephalitis,...

  8. Cerebrospinal fluid monoamine metabolites and suicide.

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


    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

  9. Chronic Treatment with a Clinically Relevant Dose of Methylphenidate Increases Glutamate Levels in Cerebrospinal Fluid and Impairs Glutamatergic Homeostasis in Prefrontal Cortex of Juvenile Rats.

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Coelho, Daniella M; Mussulini, Ben Hur; Pereira, Mery S L; Parisi, Mariana M; Barbé-Tuana, Florencia; de Oliveira, Diogo L; Vargas, Carmen R; Wyse, Angela T S


    The understanding of the consequences of chronic treatment with methylphenidate is very important since this psychostimulant is extensively prescribed to preschool age children, and little is known about the mechanisms underlying the persistent changes in behavior and neuronal function related with the use of methylphenidate. In this study, we initially investigate the effect of early chronic treatment with methylphenidate on amino acids profile in cerebrospinal fluid and prefrontal cortex of juvenile rats, as well as on glutamatergic homeostasis, Na(+),K(+)-ATPase function, and balance redox in prefrontal cortex of rats. Wistar rats at early age received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9 % saline solution (controls), once a day, from the 15th to the 45th day of age. Twenty-four hours after the last injection, the animals were decapitated and the cerebrospinal fluid and prefrontal cortex were obtained. Results showed that methylphenidate altered amino acid profile in cerebrospinal fluid, increasing the levels of glutamate. Glutamate uptake was decreased by methylphenidate administration, but GLAST and GLT-1 were not altered by this treatment. In addition, the astrocyte marker GFAP was not altered by MPH. The activity and immunocontent of catalytic subunits (α1, α2, and α3) of Na(+),K(+)-ATPase were decreased in prefrontal cortex of rats subjected to methylphenidate treatment, as well as changes in α1 and α2 gene expression of catalytic α subunits of Na(+),K(+)-ATPase were also observed. CAT activity was increased and SOD/CAT ratio and sulfhydryl content were decreased in rat prefrontal cortex. Taken together, our results suggest that chronic treatment with methylphenidate at early age induces excitotoxicity, at least in part, due to inhibition of glutamate uptake probably caused by disturbances in the Na(+),K(+)-ATPase function and/or in protein damage observed in the prefrontal cortex. PMID:26001762

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

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


    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...

  11. Malignancy markers in the cerebrospinal fluid.

    Koskiniemi, M


    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

  12. Extracranial repair of cerebrospinal fluid otorhinorrhea

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


    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 approach on neuro-oncology

    Helio Rodrigues Gomes


    Full Text Available Central nervous system (CNS involvement is a major complication of haematological and solid tumors with an incidence that ranges from 10% in solid malignances up to 25% in specific leukaemia or lymphoma subtypes. Cerebrospinal fluid (CSF patterns are unspecific. Though CSF cytology has a high specificity (up to 95%, its sensitivity is generally less than 50% and no diagnostic gold standard marker is available, yet. New technologies such as flow cytometry, molecular genetics and newer biomarkers may improve diagnostic sensitivity and specificity, leading to the CNS involvement diagnosis, and consequently, to an effective prophylaxis and successful treatment.

  14. Extracranial repair of cerebrospinal fluid otorhinorrhea

    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%

  15. Cerebrospinal fluid stasis and its clinical significance.

    Whedon, James M; Glassey, Donald


    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

  16. Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study

    Brouillette, Ashley M.; Gülin Öz; Gomez, Christopher M.


    Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau, α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, an...

  17. Imhotep and the discovery of cerebrospinal fluid.

    Blomstedt, Patric


    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. Imhotep and the Discovery of Cerebrospinal Fluid

    Patric Blomstedt


    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.

  19. Proteome analysis of chick embryonic cerebrospinal fluid.

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


    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

  20. Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer's disease.

    Liguori, Claudio; Nuccetelli, Marzia; Izzi, Francesca; Sancesario, Giuseppe; Romigi, Andrea; Martorana, Alessandro; Amoroso, Chiara; Bernardini, Sergio; Marciani, Maria Grazia; Mercuri, Nicola Biagio; Placidi, Fabio


    The orexin system has been investigated in patients affected by mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by measuring orexin-A concentrations in the cerebrospinal fluid (CSF), and correlated to subjective and objective sleep parameters, quantified by questionnaires and polysomnography, respectively. Twenty drug-naïve patients with MCI due to AD were studied and compared with a population of 26 age and/or sex matched controls, divided into subgroups on the basis of the Pittsburgh Sleep Quality Index (PSQI) score. Increased CSF-orexin levels were detected in patients with MCI due to AD in comparison with controls (p complaints (PSQI ≥5, n = 10) compared with MCI patients with a regular sleep-wake cycle (PSQI complaints, PSQI ≥5, n = 11, p complaints, PSQI <5, n = 15, p < 0.001). Moreover, REM sleep was reduced in MCI patients compared with controls (p < 0.01), and had a negative correlation coupled with a reciprocal influence at the multiple regression analysis with CSF-orexin levels (R = -0.65; β = -8.90). REM sleep disruption and sleep fragmentation are related to higher CSF-orexin levels in patients with MCI due to AD, thus suggesting that the orexin system may be involved even in the earliest stages of AD, resulting in prolonged sleep latency, reduced sleep efficiency, and REM sleep impairment. PMID:26973111

  1. Diagnostic value of circulating tumor cells in cerebrospinal fluid

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


    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).

  2. Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid

    Koethe, Dagmar; Schreiber, Daniela; Giuffrida, Andrea; Mauss, Christian; Faulhaber, Johannes; Heydenreich, Bernd; Hellmich, Martin; Graf, Rudolf; Klosterkötter, Joachim; Piomelli, Daniele; Leweke, F. Markus


    This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinal fluid (CSF) samples were obtained from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased levels of oleoylethanolamide in CSF (P = 0.011) but not in serum (P = 0.068) after 24 h of sleep deprivation. Oleoyleth...

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

    Zhengnian Ding; Weixing Hu


    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.

  4. Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.

    Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Romano, Simone; Fusco, Letizia; Cavaletti, Guido; Melcangi, Roberto Cosimo


    Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3α-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3α-diol, 3β-diol and 17β-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'. PMID:24717976

  5. Patients with depression display cytokine levels in serum and cerebrospinal fluid similar to patients with diffuse neurological symptoms without a defined diagnosis

    Hestad, Knut A; Engedal, Knut; Whist, Jon Elling; Aukrust, Pål; Farup, Per G; Mollnes, Tom Eirik; Ueland, Thor


    Introduction Several reports indicate that inflammation may play a role in depression and demonstrate enhanced systemic levels of inflammatory mediators. We hypothesized that 44 patients with a diagnosis of depression would present with a specific and different serum and cerebrospinal fluid (CSF) cytokine profile compared to 21 patients with diffuse neurological symptoms, of whom 15 had fatigue as a major symptom, but no change in emotional state. Methods The diagnoses of the patients with depression were according to the International Classification of Diseases, tenth edition (F32–34 spectra). Cytokine profiles in serum and CSF were determined by multiplex analysis, including 27 cytokines, chemokines, and growth factors. Results No differences could be found between the two groups studied regarding cytokine levels in serum or CSF except for serum interleukin (IL)-1 receptor antagonist that was lower in the depression group. There were only four high correlations (>0.4) between serum and CSF levels of the cytokines, reflecting independent synthesis and turnover in these two compartments. In the control group, fatigue was associated with increased IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor, and interferon-γ (all P<0.01). Conclusion Patients with depression had a similar cytokine profile as nondepressive patients, both systemically and in CSF. Fatigue was associated with higher levels of some inflammatory markers in the control group. It is possible that the presence of fatigue in a large proportion of patients and controls could contribute to the lack of difference in cytokine levels between these two groups. PMID:27110115

  6. Cerebrospinal fluid space alterations in melancholic depression.

    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

  7. Cerebrospinal fluid may mediate CNS ischemic injury

    Soriano Sulpicio G


    Full Text Available Abstract Background The central nervous system (CNS is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. Methods Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1 CSF depletion, 2 CSF replenishment at 0 mmHg intracranial pressure (ICP, and 3 replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC albumin. Results The severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion. Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg. Conclusion We conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective.

  8. Dynamic evolution of D-dimer level in cerebrospinal fluid predicts poor outcome in patients with spontaneous intracerebral hemorrhage combined with intraventricular hemorrhage.

    Chen, Chih-Wei; Wu, En-Hsuan; Huang, Judy; Chang, Wen-Tsan; Ao, Kam-Hou; Cheng, Tain-Junn; Yang, Wuyang


    The risk of mortality in patients with intracerebral hemorrhage (ICH) significantly increases when complicated by intraventricular hemorrhage (IVH). We hypothesize that serial measurement of cerebrospinal fluid (CSF) D-dimer levels in patients with both ICH and IVH may serve as an early marker of IVH severity. We performed a prospective study of 43 consecutive ICH patients combined with IVH and external ventricular drainage placement admitted in our institution from 2005-2006. IVH severity (Graeb score) and fibrinolytic activity were evaluated continuously for 7days using CT scans and CSF D-dimer levels. The primary outcome was 30day mortality. Overall 30day mortality was 26% (n=11), with eight deaths (72.7%) after 3days (D3). Graeb score and CSF D-dimer on admission (D0) were not significantly different between survivors and non-survivors. The temporal profiles of both parameters were distinctly different, with a downward trend in survivors and an upward trend in non-survivors. A mortality rate of 54% was observed between D0-D3 when both scores increased during this interval. In contrast, the mortality was only 4% when both measures decreased during this interval. Early phase (D0-D3) CSF D-dimer or Graeb score change demonstrated high sensitivity of 88% and specificity of 81% when predicting 30day mortality. Early phase CSF D-dimer change in patients with both ICH and IVH is accurate in predicting mortality and may be utilized as a cost-effective surrogate indicator of IVH severity. Serial monitoring of CSF D-dimer dynamic changes is useful for early identification of patients with hematoma progression and poor outcome. PMID:27050917

  9. Levels of 17beta-Hydroxysteroid Dehydrogenase Type 10 in Cerebrospinal Fluid of People with Mild Cognitive Impairment and Various Types of Dementias

    Krištofíková, Z.; Říčný, J.; Vyhnálek, M.; Hort, J.; Laczó, J.; Šírová, J.; Klaschka, Jan; Řípová, D.


    Roč. 48, č. 1 (2015), s. 105-114. ISSN 1387-2877 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant ostatní: GA MŠk(CZ) ED2.1.00/03.0078; Prague Psychiatric Center (CZ) MH CZ–DRO: 00023752 Institutional support: RVO:67985807 Keywords : 17beta-HSD10 * Alzheimer’s disease * amyloid-beta peptides * biomarker * cerebrospinal fluid Subject RIV: FH - Neurology Impact factor: 4.151, year: 2014

  10. Genome-wide association reveals genetic effects on human Aβ42 and τ protein levels in cerebrospinal fluids: a case control study

    Schellenberg Gerard D


    Full Text Available Abstract Background Alzheimer's disease (AD is common and highly heritable with many genes and gene variants associated with AD in one or more studies, including APOE ε2/ε3/ε4. However, the genetic backgrounds for normal cognition, mild cognitive impairment (MCI and AD in terms of changes in cerebrospinal fluid (CSF levels of Aβ1-42, T-tau, and P-tau181P, have not been clearly delineated. We carried out a genome-wide association study (GWAS in order to better define the genetic backgrounds to these three states in relation to CSF levels. Methods Subjects were participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI. The GWAS dataset consisted of 818 participants (mainly Caucasian genotyped using the Illumina Human Genome 610 Quad BeadChips. This sample included 410 subjects (119 Normal, 115 MCI and 176 AD with measurements of CSF Aβ1-42, T-tau, and P-tau181P Levels. We used PLINK to find genetic associations with the three CSF biomarker levels. Association of each of the 498,205 SNPs was tested using additive, dominant, and general association models while considering APOE genotype and age. Finally, an effort was made to better identify relevant biochemical pathways for associated genes using the ALIGATOR software. Results We found that there were some associations with APOE genotype although CSF levels were about the same for each subject group; CSF Aβ1-42 levels decreased with APOE gene dose for each subject group. T-tau levels tended to be higher among AD cases than among normal subjects. From adjusted result using APOE genotype and age as covariates, no SNP was associated with CSF levels among AD subjects. CYP19A1 'aromatase' (rs2899472, NCAM2, and multiple SNPs located on chromosome 10 near the ARL5B gene demonstrated the strongest associations with Aβ1-42 in normal subjects. Two genes found to be near the top SNPs, CYP19A1 (rs2899472, p = 1.90 × 10-7 and NCAM2 (rs1022442, p = 2.75 × 10-7 have been reported as genetic

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

    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)

  12. Population Pharmacokinetics of Abacavir in Plasma and Cerebrospinal Fluid

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


    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.

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

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


    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 was...

  14. Entamoeba histolytica meningoencephalitis diagnosed by trophozoites in cerebrospinal fluid

    Goh, L M L; Marrone, J R


    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.

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



    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.

  16. Arachnoid cysts do not contain cerebrospinal fluid: A comparative chemical analysis of arachnoid cyst fluid and cerebrospinal fluid in adults

    Haaland Øystein A


    Full Text Available Abstract Background Arachnoid cyst (AC fluid has not previously been compared with cerebrospinal fluid (CSF from the same patient. ACs are commonly referred to as containing "CSF-like fluid". The objective of this study was to characterize AC fluid by clinical chemistry and to compare AC fluid to CSF drawn from the same patient. Such comparative analysis can shed further light on the mechanisms for filling and sustaining of ACs. Methods Cyst fluid from 15 adult patients with unilateral temporal AC (9 female, 6 male, age 22-77y was compared with CSF from the same patients by clinical chemical analysis. Results AC fluid and CSF had the same osmolarity. There were no significant differences in the concentrations of sodium, potassium, chloride, calcium, magnesium or glucose. We found significant elevated concentration of phosphate in AC fluid (0.39 versus 0.35 mmol/L in CSF; p = 0.02, and significantly reduced concentrations of total protein (0.30 versus 0.41 g/L; p = 0.004, of ferritin (7.8 versus 25.5 ug/L; p = 0.001 and of lactate dehydrogenase (17.9 versus 35.6 U/L; p = 0.002 in AC fluid relative to CSF. Conclusions AC fluid is not identical to CSF. The differential composition of AC fluid relative to CSF supports secretion or active transport as the mechanism underlying cyst filling. Oncotic pressure gradients or slit-valves as mechanisms for generating fluid in temporal ACs are not supported by these results.

  17. Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study.

    Brouillette, Ashley M; Öz, Gülin; Gomez, Christopher M


    Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau, α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that α-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C. PMID:26265793

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

    Bo Zhou


    Full Text Available 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.

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

    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


    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.

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

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


    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

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

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


    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,

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

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen; Khorooshi, Reza; Owens, Trevor


    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 was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown. PMID:26339679

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

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


    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

  4. Gentamicin penetration into cerebrospinal fluid in experimental Haemophilus influenzae meningitis.

    Smith, A. L.; Daum, R S; Siber, G R; Scheifele, D. W.; Syriopoulou, V P


    We studied the effect of meningitis and the method of parenteral gentamicin administration (intramuscular injection, a 30-min intravenous infusion, or intravenous bolus administration) on achievable concentrations of drug in cerebrospinal fluid (CSF). In normal animals, only intravenous bolus administration of 2 to 8 mg/kg produced a gentamicin concentration of greater than 0.1 microgram/ml in CSF in some animals. All CSF samples contained less than the limit of detection (0.1 microgram/ml) a...

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

    Anders Jens; Pietsch Stefan; Bauer Heike I; Kluge Harald H; Kluge Wolfram H; Venbrocks Rudolf A


    Abstract Background Most test systems for acetylcholinesterase activity (E.C. are using toxic inhibitors (BW284c51 and iso-OMPA) to distinguish the enzyme from butyrylcholinesterase (E.C. 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 Pharmaco...

  6. Experiences with cerebrospinal fluid analysis in Dutch memory clinics

    Spies, P.E.; Slats, D.; Ramakers, I.; Verhey, F.R.J.; Olde Rikkert, M.G.M.


    BACKGROUND: Evidence on cerebrospinal fluid (CSF) analysis to demonstrate Alzheimer's disease has not yet been implemented in diagnostic guidelines. METHODS: We investigated the use of CSF analysis in a survey amongst all known memory clinics in the Netherlands, of which 85 of 113 (75.2%) responded. RESULTS: Sixty per cent of respondents used CSF analysis in 5% (median) of patients. The analysis almost always confirmed the working diagnosis in 68.4% and sometimes changed it in 28.2%. Complica...

  7. Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder

    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


    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...

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

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


    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...

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

    Sandro Luiz de Andrade Matas


    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.

  10. Vitamin B6 in plasma and cerebrospinal fluid of children

    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.


    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...

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

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


    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.

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

    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

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

    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.

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

    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


    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

  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

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


    performance had evidence of atrophy in the hippocampus and cortical areas, significantly lower cerebrospinal fluid levels of amyloid beta amino acid 1-42 (p<0.001) and higher cerebrospinal fluid total tau levels (p<0.05) compared to the group performing well on the DRT tests. CONCLUSION: Old, memory...

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

    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.


    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...

  17. Cerebrospinal fluid dynamics in Chiari malformation associated with syringomyelia

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


    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

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

    Anders Jens


    Full Text Available Abstract Background Most test systems for acetylcholinesterase activity (E.C. are using toxic inhibitors (BW284c51 and iso-OMPA to distinguish the enzyme from butyrylcholinesterase (E.C. 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.

  19. Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

    Assenzio, Barbara; Martin, Erica L.; Stankevicius, Edgaras; Civiletti, Federica; Fontanella, Marco; Boccaletti, Riccardo; Berardino, Maurizio; Mazzeo, AnnaTeresa; Ducati, Alessandro; Simonsen, Ulf; Mascia, Luciana


    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 patients

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

    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.

  1. Recurrent purulent meningitis associated with cerebrospinal fluid leak from the idiopathic oval window

    Purulent meningitis recurred 6 times in a 7-year-old boy. There was unilateral serous rhinorrhea, for which right cerebrospinal fluid otorrhea was suspected on 111In DTPA cisternogram. Examination of the right tympanum through the mastoid antrum revealed a fistula in the stapes foot plate, causing cerebrospinal fluid leakage. The stapes was removed and was replaced with the muscle and fascia. As a result, cerebrospinal fluid leakage discontinued, followed by a satisfactory course. (Chiba, N.)

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

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


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

    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.

  4. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    In this work, the spatial localization of leucocytes, bacteria, and erythrocytes in the crystal pattern of a dried droplet of cerebrospinal fluid (CSF) is established. Characteristic lines are detected and identified in the Raman spectrum of the CSF that point to the presence of pathologic cells therein and can be used in a timely way to diagnose meningitis, the spectroscopic sample preparation procedure being simple enough. A dry CSF sample retains its characteristic spectral features for no less than three days, which is important for its safe keeping and transportation, and also for the computer processing of its spectra. (letter)

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

    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)

  6. Diagnosis of chordoma by cytologic examination of cerebrospinal fluid.

    Marigil, M A; Pardo-Mindan, F J; Joly, M


    This is a case report of a 44-year-old man with a chordoma of the clivus that caused dysphonia, low back pain, and urinary and fecal incontinence. The diagnosis was made by cytologic study of the CSF, which demonstrated vacuolated malignant cells. The patient was treated with intrathecal methotrexate, dexamethasone, and radiotherapy. At autopsy extensive dissemination of chordoma was found at the base of the brain, in the ventricles, and in the leptomeninges of the spinal cord. This is the sixth reported case of intrathecal dissemination of a chordoma and the first diagnosed by cytology of the cerebrospinal fluid. PMID:6881106

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

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


    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

  8. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    Warrington, Junie P


    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

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

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


    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...

  10. Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV-1 infection

    Deeks Steven G; Hagberg Lars; Rosengren Lars; Gisslén Magnus; Price Richard W


    Abstract Background The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy. We identified subjects who had CSF HIV ...

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

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


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

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


    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. Presaturation tagging of neuraxis motion and cerebrospinal fluid circulation

    This paper describes motion of the spinal cord and of the cerebrospinal fluid (CSF) examined with use of spatially selective presaturation pulses to tag portions of tissue or fluid. The plane of presaturation was perpendicular to the imaging plane and less than 1 mm thick. The observation of pulsatile motion of the tags in the cervical cord relative to stationary tissue provides a direct visual demonstration of actual cord deflection that can be applied to the evaluation of diseases restricting cord motion by tethering or compression. Visualization of motion of the tags within the CSF directly shows the direction and magnitude of flow and can be useful for the noninvasive assessment of diseases involving the CSF circulation

  14. Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

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


    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.

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

    Miyajima, Masakazu; Arai, Hajime


    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

  16. A porous silicon immunoassay platform for fluorometric determination of α-synuclein in human cerebrospinal fluid

    Levels of total and/or oligomeric α-synuclein may be used as a biomarker tool to aid in the diagnosis and development of new disease-modifying therapies. We report here on a porous silicon antibody microarray for the fluorimetric determination of cerebrospinal fluid levels of total α-synuclein, a protein involved the pathology of Parkinson’s disease. The surface of porous silicon has a 3-dimensional macro- and nanoporous structure, and this offers a large binding capacity for capturing probe molecules. Porous silicon also warrants efficient immobilization of antibodies by surface adsorption, and does not require chemical immobilization. The platform requires 10 μL of cerebrospinal fluid, and each test requires 4 h for assay only (including immobilization of capturing antibody). The limit of detection is 35 pg mL−1 of α-synuclein in cerebrospinal fluid, and the dynamic analytical range extends from 0.01 to 100 ng·mL−1. (author)

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

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


    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.


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


    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.

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

    Abdullah Kaya


    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

  20. Massive Cerebrospinal Fluid Leak of the Temporal Bone

    Giannicola Iannella


    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. Quantitative Proteomics of Vestibular Schwannoma Cerebrospinal Fluid: A Pilot Study.

    Kazemizadeh Gol, Mohammad Abraham; Lund, Troy C; Levine, Samuel C; Adams, Meredith E


    This pilot study aimed to identify candidate proteins for future study that are differentially expressed in vestibular schwannoma (VS) cerebrospinal fluid (CSF) and to compare such proteins with those previously identified in perilymph and specimen secretions. CSF was collected intraoperatively prior to removal of untreated sporadic VS (3 translabyrinthine, 3 middle cranial fossa approaches) and compared with reference CSF samples. After proteolytic digestion and iTRAQ labeling, tandem mass spectrometry with ProteinPilot was used to identify candidate proteins. Of the 237 proteins detected, 13 were dysregulated in ≥3 of the 6 VS patients versus controls, and 13 were dysregulated (12 up, 1 down) in samples from patients with class D versus class B hearing. Four perilymph proteins of interest were dysregulated in ≥1 VS CSF samples. Thus, 26 candidate VS CSF biomarkers were identified that should be considered in future VS biomarker and tumor pathophysiology investigations. PMID:26932958

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

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


    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

  3. Drug delivery to the human brain via the cerebrospinal fluid

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

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

    V. B. Musatov; Yakovlev, A. A.; S. G. Andreeva; M. V. Ivanova


    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 opportunist...

  5. Equine cerebrospinal fluid: reference values of normal horses.

    Mayhew, I G; Whitlock, R H; Tasker, J B


    Cerebrospinal fluid (CSF) samples were collected from the atlanto-occipital (AO) and lumbosacral (LS) subarachnoid spaces of 24 horses and 21 ponies that had no clinical evidence of neurologic disease. Depth of needle insertion, pressures, refractive index, rapid reagent strip test (protein, glucose, blood, pH) results, cell counts, content of protein, glucose, sodium, potassium, chloride, calcium, phosphorus, urea nitrogen, and cholesterol, and activities of creatine phosphokinase, aspartate transaminase, lactic dehydrogenase, and alkaline phosphatase were determined. The resulting clinical reference values obtained were discussed in light of the published normal values for CSF from horses, other animals, and man. White cell counts in CSF were found to be from 0 to 6/microliters. Values for protein content were distributed between wider limits than previously reported values. The LS-AO difference is proposed as a criterion for clinical evaluation of CSF protein content. Ponies were found to have more protein in their CSF than did the horses, and CSF from the LS site contained more glucose than that from the AO site. The CSF electrolyte composition was similar to that of previous reports. Enzyme activities in equine CSF are reported for the 1st time. PMID:911095

  6. Molecular biomarkers in cerebrospinal fluid of multiple sclerosis patients.

    Fitzner, Brit; Hecker, Michael; Zettl, Uwe Klaus


    Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, usually occurring in young adults and leading to disability. Despite the progress in technology and intensive research work of the last years, diagnosing MS can still be challenging. A heterogenic and complex pathophysiology with various types of disease courses makes MS unique for each patient. There is an urgent need to identify markers facilitating rapid and accurate diagnosis and prognostic assessments with regard to optimal therapy for each MS patient. Cerebrospinal fluid (CSF) is an outstanding source of specific markers related to MS pathology. Molecules reflecting specific pathological processes, such as inflammation, cellular damage, and loss of blood-brain-barrier integrity, are detectable in CSF. Clinically used biomarkers of CSF are oligoclonal bands, IgG-index, measles-rubella-zoster-reaction, anti-aquaporin 4 antibodies, and antibodies against John Cunningham virus. Many other potential biomarkers have been proposed in recent years. In this review we examine the current scientific knowledge on CSF molecular markers that could guide diagnosis and discrimination of different MS forms, support treatment decisions, or be helpful in monitoring and predicting disease progression, therapy response, and complications such as opportunistic infections. PMID:26071103

  7. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

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


    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

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

    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.

  9. Cystatin C in cerebrospinal fluid as a biomarker of ALS.

    Tsuji-Akimoto, Sachiko; Yabe, Ichiro; Niino, Masaaki; Kikuchi, Seiji; Sasaki, Hidenao


    Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy. PMID:19444952

  10. Virtual MRI endoscopy of the intracranial cerebrospinal fluid spaces

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


    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.

  11. Dynamic oxygen-enhanced MRI of cerebrospinal fluid.

    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.

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

    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


    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

  13. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    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.


    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.

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

    Bottan, Simone; Poulikakos, Dimos; Kurtcuoglu, Vartan


    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

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

    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.


    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

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

    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


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

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


    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

  18. Enterovirus-D68 in the Cerebrospinal Fluid of Two Children with Aseptic Meningitis.

    Esposito, Susanna; Lunghi, Giovanna; Zampiero, Alberto; Tagliabue, Claudia; Orlandi, Anna; Torresani, Erminio; Niesters, Hubert; Principi, Nicola


    This case report describes two previously healthy children with aseptic meningitis whose cerebrospinal fluid was positive for enterovirus-D68, which indicates direct involvement of this infectious agent in the development of this neurologic disease. PMID:26859634

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

    Mariia Zharova; Pavel Umriukhin; Natalia Veiko


    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...

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

    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

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

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


    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

  2. Evaluation of cerebrospinal fluid in Southeast Asian refugees with reactive serologic tests for syphilis.

    Buchwald, D; Collier, A.C.; Lukehart, S A; Kith, P; Goldstein, E; Hooton, T M


    To determine the prevalence of cerebrospinal fluid abnormalities in Southeast Asian refugees with reactive serologic tests for syphilis, we evaluated 65 patients, 36 prospectively and 29 retrospectively, in a primary care clinic. Information was collected on history of treponemal infections, neurologic symptoms and signs, and total protein concentration, leukocyte count, and the VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all patients for whom data were availabl...

  3. Cerebrospinal Fluid Alzheimer Markers in Depressed Elderly Subjects with and without Alzheimer's Disease

    Kramberger, Milica Gregoric; Jelic, Vesna; Kåreholt, Ingemar; Enache, Daniela; Eriksdotter Jönhagen, Maria; Winblad, Bengt; Aarsland, Dag


    Background The aim of this study was to explore the relationship between cerebrospinal fluid Alzheimer's disease (AD) markers and depression in elderly people. Method We included subjects with AD as well as persons with subjective cognitive impairment and normal cognition. Depression was assessed with the Cornell Scale for Depression in Dementia, and a cut-off score of >6 was used to define depression. Cerebrospinal fluid was analyzed using commercially available assays for β-amyloid 1–42, to...

  4. Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis


    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

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

    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)

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

    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)

  7. Progressive Differentiation and Instructive Capacities of Amniotic Fluid and Cerebrospinal Fluid Proteomes following Neural Tube Closure.

    Chau, Kevin F; Springel, Mark W; Broadbelt, Kevin G; Park, Hye-Yeon; Topal, Salih; Lun, Melody P; Mullan, Hillary; Maynard, Thomas; Steen, Hanno; LaMantia, Anthony S; Lehtinen, Maria K


    After neural tube closure, amniotic fluid (AF) captured inside the neural tube forms the nascent cerebrospinal fluid (CSF). Neuroepithelial stem cells contact CSF-filled ventricles, proliferate, and differentiate to form the mammalian brain, while neurogenic placodes, which generate cranial sensory neurons, remain in contact with the AF. Using in vivo ultrasound imaging, we quantified the expansion of the embryonic ventricular-CSF space from its inception. We developed tools to obtain pure AF and nascent CSF, before and after neural tube closure, and to define how the AF and CSF proteomes diverge during mouse development. Using embryonic neural explants, we demonstrate that age-matched fluids promote Sox2-positive neurogenic identity in developing forebrain and olfactory epithelia. Nascent CSF also stimulates SOX2-positive self-renewal of forebrain progenitor cells, some of which is attributable to LIFR signaling. Our Resource should facilitate the investigation of fluid-tissue interactions during this highly vulnerable stage of early brain development. PMID:26702835

  8. Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid

    He, Ping [Johns Hopkins University, Department of Biomedical Engineering, Baltimore, MD (United States); Kramer, Kim; Cheung, Nai-Kong V. [Memorial Sloan-Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Smith-Jones, Peter; Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Zanzonico, Pat; Humm, John [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York, NY (United States)


    Radioimmunotherapy (RIT) using {sup 131}I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of {sup 131}I-3F8 and to identify limiting factors that may impact therapeutic ratio. Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[C{sub IAR}]), (2) that of the unbound antibody AUC[C{sub IA}], and (3) their therapeutic ratio (AUC[C{sub IAR}]/AUC[C{sub IA}]). Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R = 0.95 {+-} 0.03). Correlations were substantially better when compared to the one-compartment model (R = 0.92 {+-} 0.11 versus 0.77 {+-} 0.21, p = 0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of {sup 131}I-3F8 from 10% to 90% increased both (AUC[C{sub IAR}]) and therapeutic ratio (AUC[C{sub IAR}]/AUC[C{sub IA}]) by 7.4 fold, (2) When extrapolated to the clinical setting, the model predicted that if {sup 131}I-3F8 could be split into 4 doses of 1.4 mg each and given at {>=}24 hours apart, an antibody affinity of K{sub D} of 4 x 10{sup -9} at 50% immunoreactivity were adequate in order to deliver {>=}100 Gy to tumor cells while keeping normal CSF exposure to <10 Gy. This model predicted that immunoreactivity, affinity and optimal scheduling of antibody injections were crucial in improving therapeutic index. (orig.)

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

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


    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.

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

    Fellmann Jere


    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.

  11. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111In-DTPA ventriculography

    Cerebrospinal fluid flow dynamics were evaluated by 111In-diethylenetriamine pentaacetic acid (111In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that 111In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis

  12. Increased digitalis-like activity in human cerebrospinal fluid after expansion of the extracellular fluid volume

    The present study was designed to determine whether acute expansion of the extracellular fluid volume influenced the digitalis-like activity of human cerebrospinal fluid (CSF), previously described. Human CSF samples, drawn before and 30 minutes after the intravenous infusion of 1 liter of either saline or glucose solutions, were assayed for digitalis-like activity by inhibition of either the 86Rb+ uptake into human erythrocytes or by the activity of a purified Na+-K+ ATPase. The CSF inhibitory activity on both systems significantly increased after the infusion of sodium solutions but did not change after the infusion of glucose. These results indicate that the digitalis-like factor of human CSF might be involved in the regulation of the extracellular fluid volume and electrolyte content and thereby in some of the physiological responses to sodium loading. 31 references, 2 figures, 1 table

  13. Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

    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


    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, ...

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



    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...

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

    V. B. Musatov


    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

  16. Experimental determination of the Stern layer thickness at the interface of the human arachnoid membrane and the cerebrospinal fluid

    The paper is part of an investigation of the electrostatic forces contributing to the interaction between colloidal molecules, suspended in the cerebrospinal fluid, with other molecules of the cerebrospinal fluid and with the surrounding environment. The study is based on experimental observations and theoretical considerations. We are reporting about the microscopic observation of particles suspended in the cerebrospinal fluid which was obtained by lumbar puncture of 27 neurosurgery patients. We found that the mean particle diameter and therefore the mean thickness of the Stern layer at the interface of the arachnoid membrane with the cerebrospinal fluid is a few micrometers. Individual variations of this diameter have been observed. (orig.)

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

    Parada, Carolina; Gato, Angel; Bueno, David


    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

  18. Neural cell adhesion molecule (NCAM) and prealbumin in cerebrospinal fluid from depressed patients

    Jørgensen, Ole Steen


    The size of the soluble form of the human cerebrospinal fluid (CSF) neural cell adhesion molecule, NCAM-sol, was by gel permeation chromatography estimated to 160-250 kDa. Within the CSF the concentration of NCAM-sol was found about 15-25% increased in lumbar fluid and 25% increased in ventricular...

  19. Indication for and value of information obtained by scintigraphy of the intracranial cerebrospinal fluid space

    56 scintigraphic examinations of the cerebrospinal fluid space for differential diagnosis of hydrocephalus as well as for the demonstration and localization of liquorrhea and of disturbances of the spinal fluid passage are reported. When using 169Yb-DTPA the procedure has proved to be very reliable and side reactions need not be expected

  20. Fluoride in cerebrospinal fluid of patients with fluorosis.

    Hu, Y H; Wu, S S


    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 ...

  1. Macrophage migration inhibitory factor in cerebrospinal fluid from patients with central nervous system infection

    Ostergaard, Christian; Benfield, Thomas


    .01). Among patients with purulent meningitis, CSF MIF levels were significantly higher in patients infected with pneumococci as compared to infection due to meningococci (11569 ng/L (8615-21935) vs. 5006 ng/L (1717-10905) respectively, P=0.02), in patients requiring assisted ventilation (10493 ng/L (5961......ABSTRACT: INTRODUCTION: Macrophage Migration Inhibitory Factor (MIF) plays an essential pathophysiological role in septic shock; however, its role in central nervous system infection (CNS) remains to be defined. METHODS: The aim of the present study was to investigate cerebrospinal fluid (CSF...... suspected of but had no evidence of CNS infection. RESULTS: CSF MIF levels were significantly higher in patients with purulent meningitis of known aetiology (8639 ng/L (3344-20600)) as compared to patients with purulent meningitis of unknown aetiology (2209 ng/L (1516-6550), Mann Whitney test, P=0.003), to...

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

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


    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 ...

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

    E. V. Stepanova


    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.

  4. Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV+ patients with syphilis

    Ronald Salamano


    Full Text Available ABSTRACT Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF, especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL, regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients.

  5. Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis

    Møllgaard, M; Vinter, Matilda Degn; Sellebjerg, F;


    BACKGROUND AND PURPOSE: The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins is......) and cognitive impairment by the Paced Auditory Serial Addition Test (P = 0.0357, linear regression) at follow-up. In a multivariate analysis of MS risk, CHI3L2 performed better than CHI3L1. CONCLUSIONS: CHI3L2 and chitotriosidase are promising biomarkers in patients with a first demyelinating episode......, immunoglobulin G index and leukocyte count were investigated. Long-term MS risk and disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite components) were examined in a retrospective cohort of 78 patients with ON as the first demyelinating episode (mean follow-up 14 years). The...

  6. Erythropoietin in the cerebrospinal fluid of patients with aneurysmal subarachnoid haemorrhage originates from the brain

    Springborg, Jacob Bertram; Sonne, Bjarne; Frederiksen, Hans Jørgen;


    Recent years' research has revealed a specific, neuroprotective erythropoietin (EPO) system in the central nervous system (CNS) that is upregulated by hypoxia. The presence and dynamics of EPO in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH) has not been investigated....... We collected a total of 83 corresponding serum and CSF samples from 18 patients with aneurysmal SAH and compared the concentrations of EPO with those of blood-derived markers of blood-brain barrier function (albumin, transferrin, alpha(2)-macroglobulin) and with those of proteins with well-known CNS...... synthesis (prealbumin, apolipoprotein E). The EPO concentration in CSF was 0.93 (0.82) mU/ml (median and inter-quartile range). Nine patients presented CSF-EPO values above 1 mU/ml. CSF levels did not correlate with serum concentrations and were independent of blood-brain barrier integrity suggesting a...

  7. Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV+ patients with syphilis.

    Salamano, Ronald; Ballesté, Raquel; Perna, Abayubá; Rodriguez, Natalia; Lombardo, Diego; García, Natalia; López, Pablo; Cappuccio, Pablo


    Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF), especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL), regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA) titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients. PMID:26982990

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

    Beyer, Natascha Helena; Lueking, Angelika; Kowald, Axel; Frederiksen, Jette Lautrup; Heegaard, Niels Henrik Helweg

    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- an...

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

    Karunarathne Suneth; Govindapala Dumitha; Udayakumara Yapa; Fernando Harshini


    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...

  10. Analgesic and thermic effects, and cerebrospinal fluid and plasma pharmacokinetics, of intracerebroventricularly administered morphine in normal and sensitized rats.

    Bhargava, H N; Villar, V M; Cortijo, J; Morcillo, E J


    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

  11. Evaluation of postmortem drug concentrations in cerebrospinal fluid compared with blood and pericardial fluid.

    Tominaga, Mariko; Michiue, Tomomi; Ishikawa, Takaki; Inamori-Kawamoto, Osamu; Oritani, Shigeki; Maeda, Hitoshi


    In forensic toxicology, body fluids are important materials not only as alternatives to blood but also for investigation of postmortem drug redistributions and pharmaco-/toxicokinetic analysis; however, there are limited data on postmortem drug distributions in cerebrospinal fluid (CSF). The present study reviewed toxicological data of autopsy cases (n=103), in which drugs were detected in CSF using gas chromatography/mass spectrometry (GC/MS), to investigate drug concentrations in CSF, compared with blood and pericardial fluid (PCF) concentrations. Oral/injected amphetamines (n=23) showed similar CSF and blood/PCF concentrations with partly lower CSF concentrations (about ×0.5-1.1). CSF concentrations of the venous anesthetic midazolam (n=7) were lower with poor correlations. Oral caffeine (n=15), acetaminophen (n=7), chlorpheniramine (n=6), dihydrocodeine (n=6), and phenobarbital (n=21) showed equivalent to lower CSF concentrations (about ×0.2-1.2), compared with blood and PCF concentrations; however, CSF phenobarbital concentrations were high in a fatal intoxication case. CSF concentrations of phenothiazine derivatives (n=29) were markedly lower (about ×0.1) than blood/PCF concentrations. The distribution of the local anesthetic lidocaine used in critical medical care (n=49) markedly varied by case. These findings suggest that CSF is useful in routine forensic toxicology as an alternative to blood as well as for investigating pharmaco-/toxicokinetics and postmortem redistributions. PMID:26218406

  12. Ethanol contamination of cerebrospinal fluid during standardized sampling and its effect on 1H-NMR metabolomics

    van der Sar, Sonia A.; Zielman, Ronald; Terwindt, Gisela M; van den Maagdenberg, Arn M.J.M.; Deelder, André M; Mayboroda, Oleg A; Meissner, Axel; Ferrari, Michel D.


    Standardization of body fluid sampling, processing and storage procedures is pivotal to ensure data quality in metabolomics studies. Yet, despite strict adherence to standard sampling guidelines, we detected variable levels of ethanol in the 1H-NMR spectra of human cerebrospinal fluid (CSF) samples (range 9.2 × 10−3–10.0 mM). The presence of ethanol in all samples and the wide range of concentrations clearly indicated contamination of the samples of some sort, which affected the 1H-NMR spectr...

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

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


    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...

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

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


    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

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

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


    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

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

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


    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

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

    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


    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

  18. Preliminary analysis of proton magnetic resonance 1D spectra of cerebrospinal fluid and brain cancer extracts

    In series of cerebrospinal fluid samples from 25 patients proton spectra of magnetic resonance were measured. The spectra were measured also for series of brain tumor tissue extracts received from another 25 patients. This paper presents an attempt to apply statistical methods of image recognition for spectra analysis of the two measured series

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

    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)


    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

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

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


    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, the...

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

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


    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

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

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


    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...

  3. Fourier analysis of cerebrospinal fluid flow velocities: MR imaging study. The Scandinavian Flow Group

    Thomsen, C; Ståhlberg, F; Stubgaard, M;


    An interleaved pseudocinematographic FLASH (fast low-angle shot) sequence with additional pulsed gradients for flow encoding was used to quantify cerebrospinal fluid (CSF) flow velocities and CSF production. Flow-dependent phase information was obtained by subtracting two differently encoded phase...

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

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


    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...

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

    Sofia Águeda


    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

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

    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.)

  7. 多梗死性痴呆患者血浆、脑脊液胰岛素含量与智能水平的相关性研究%Assay of relationship between plasma and cerebrospinal fluid insulin levels and intelligent level in patients with multi infarct dementia

    周红杰; 王景周; 高东; 张莉莉; 李敏


    Objective To study the change of plasma and cerebrospinal fluid (CSF) insulin levels and the relationship to intellectual level in patients with multi infarct dementia (MID).Methods The concentration of insulin in plasma and CSF was determined by RIAs in 55 patients with MID. 72 patients with cerebral infarction(CI) and 32 normal subjects were used as controls. Mini mental state examination (MMSE) was used to examine the intellectual level of patients, with DSM IV diagnosis standard and Hachinski Ischemia Score as references. Results The patients in MID had significantly higher plasma insulin level than that in normal controls ( P < 0.01 ), but lower CSF insulin and reduced CSF to plasma insulin ratio (P< 0.01). There was a positively correlated between CSF to plasma insulin ratio and MMSE score for MID as a whole. The patients in CI acute phase group had a higher plasma insulin levels than that in normal controls ( P < 0.05 ) , but CSF to plasma insulin ratio differed statistically from either MID acute episode group or stationary phase group ( P < 0.01 ). Conclusion The change of plasma and CSF insulin levels may be one of the pathophysiological mechanisms that bring about intellectual level decline in MID. CSF to plasma insulin ratio may be used as a marker of intellectual level declining for patients with MID.

  8. Myelin basic protein determination in cerebro-spinal fluid of children with tuberculous meningitis

    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)

  9. Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease

    Tarawneh, Rawan; Head, Denise; Allison, Samantha; Buckles, Virginia; Fagan, Anne M.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.


    IMPORTANCE Measures of neuronal loss are likely good surrogates for clinical and radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in predicting disease progression and guiding outcome assessments and prognostic decisions in clinical trials of disease-modifying therapies. Visinin-like protein 1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury in AD. OBJECTIVE To investigate the usefulness of CSF VILIP-1, tau, p-tau181, and Aβ42 levels in predicting rates of whole-brain and regional atrophy in early AD and cognitively normal control subjects over time. DESIGN, SETTING, AND PARTICIPANTS Longitudinal observational study of brain atrophy in participants with early AD and cognitively normal controls. Study participants had baseline CSF biomarker measurements and longitudinal magnetic resonance imaging assessments for a mean follow-up period of 2 to 3 years. Mixed linear models assessed the ability of standardized baseline CSF biomarker measures to predict rates of whole-brain and regional atrophy over the follow-up period. The setting was The Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine in St Louis. Participants (mean age, 72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23) and cognitively normal controls (n = 64) who were enrolled in longitudinal studies of healthy aging and dementia. The study dates were 2000 to 2010. MAIN OUTCOMES AND MEASURES Correlations between baseline CSF biomarker measures and rates of whole-brain or regional atrophy in the AD and control cohorts over the follow-up period. RESULTS Baseline CSF VILIP-1, tau, and p-tau181 levels (but not Aβ42 levels) predicted rates of whole-brain and regional atrophy in AD over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P = .006), hippocampal (P = .01), and

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

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


    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

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

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


    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

  12. Significance of cerebrospinal fluid lactate level in diagnosing neonatal bacterial meningitis%脑脊液乳酸水平对新生儿细菌性脑膜炎的诊断价值

    赵翠; 张澜; 刘宁; 张鹏; 梅枚; 胡黎园; 周文浩; 曹云; 程国强


    目的:探讨脑脊液乳酸水平在新生儿细菌性脑膜炎诊断中的价值。方法收集2014年1月至2015年3月复旦大学附属儿科医院新生儿科住院患儿脑脊液。采用血气分析仪检测脑脊液乳酸、葡萄糖水平。采用纸片法检测血糖水平及脑脊液葡萄糖水平。根据脑脊液培养、细胞数及临床表现将纳入患儿分为细菌性脑膜炎组(观察组)与非细菌性脑膜炎组(对照组),利用 Stata 12.0软件对数据进行统计学分析。结果共纳入93例患者,其中观察组16例,对照组77例。观察组脑脊液乳酸、脑脊液乳酸/脑脊液糖比值中位数分别为4.2 mmol/ L、2.32,高于对照组的1.3 mmol/ L、0.52,差异有统计学意(Z =-6.19、5.92,P 均﹤0.05);观察组脑脊液糖、脑脊液糖/血糖比值中位数分别为1.25 mmol/ L、0.44,较对照组(2.50 mmol/ L、0.81)明显低,差异有统计学意义(Z =4.97、4.43,P 均﹤0.05)。作为诊断细菌性脑膜炎指标时,脑脊液乳酸最佳界值2.2 mmol/ L,其阳性预测值(PPV)为72.7%、阴性预测值(NPV)为100.0%;脑脊液乳酸/脑脊液糖最佳界值1.24,PPV 为94.1%、NPV 为100.0%;脑脊液糖最佳界值2.0 mmol/ L,其 PPV 为65.0%、NPV 为96.9%;脑脊液糖/血糖比值最佳界值0.6,其 PPV 为60.0%、NPV 为96.9%。结论脑脊液乳酸可作为新生儿细菌性脑膜炎诊断指标之一。%Objective To study the significance of the cerebrospinal fluid(CSF)lactate level in diagnosing neonatal bacterial meningitis(BM). Methods The CSF samples were collected from neonates admitted to Neonatal Ward of Children's Hospital of Fudan University between January 2014 and March 2015. CSF lactate and glucose con-centrations were measured with blood - gas analyzer. CSF and serum glucose levels were measured with glucometer. The enrolled neonates were divided into 2 groups based on CSF culture,CSF white blood cells(WBCs)and clinical

  13. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus.

    Ho, Roger C; Thiaghu, C; Ong, Huiyi; Lu, Yanxia; Ho, Cyrus S; Tam, Wilson W; Zhang, Melvyn W


    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

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

    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)

  15. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

    Hornig, M; Gottschalk, G; Peterson, D L; Knox, K K; Schultz, A F; Eddy, M L; Che, X; Lipkin, W I


    Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β, suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity. PMID:25824300

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

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


    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil® (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 ...

  17. Detection of Antibodies to Brucella Cytoplasmic Proteins in the Cerebrospinal Fluid of Patients with Neurobrucellosis

    Baldi, Pablo C.; Araj, George F.; Racaro, Graciela C.; Wallach, Jorge C.; Fossati, Carlos A.


    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...

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

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


    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.

  19. Mycophenolic acid inhibits replication of Type 2 Winnipeg, a cerebrospinal fluid-derived reovirus isolate

    Hermann, Laura L.; Coombs, Kevin M.


    BACKGROUND: The role of reoviruses in human disease is uncertain. Most identified cases are sporadic and asymptomatic or produce minor upper respiratory or gastrointestinal symptoms. In November 1997, a reovirus was isolated from the cerebrospinal fluid of a severe combined immune deficient infant in Winnipeg, Manitoba. RNA characterization and sequencing studies demonstrated this reovirus isolate to be unique. Thus, the virus was named Type 2 Winnipeg (T2W).OBJECTIVES: Mycophenolic acid (MPA...


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


    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...

  1. An evaluation of cerebrospinal fluid oligoclonal banding confirmed by immunofixation on agarose gel.

    George, P M; Lorier, M A; Donaldson, I M


    The cerebrospinal fluid (CSF) from 115 consecutive patients undergoing diagnostic lumbar puncture or myelography was examined to determine the usefulness of immunofixation, following agarose gel electrophoresis, in the detection of oligoclonal IgG. All electrophoretic patterns were evaluated with and without immunofixation, and the interpretation of 9% of specimens was altered by immunofixation. The demonstration of oligoclonal IgG was shown to be more reliable in the diagnosis of multiple sc...

  2. Cerebrospinal fluid viral breakthrough in two HIV-infected subjects on darunavir/ritonavir monotherapy

    Gisslén, Magnus; Fuchs, Dietmar; Hagberg, Lars; Svennerholm, Bo; Zetterberg, Henrik


    Darunavir/ritonavir monotherapy maintains HIV suppression in most patients who have achieved an undetectable viral load on combination antiretroviral treatment, and is increasingly used in the clinic. However, concerns have been raised about the effectiveness of ritonavir-boosted protease inhibitor (PI/r) monotherapy in the prevention of HIV replication in the central nervous system (CNS). Here we report the cases of 2 patients on darunavir/r maintenance monotherapy with cerebrospinal fluid v...

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

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


    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...

  4. Development of a Cerebrospinal Fluid Lateral Reservoir Model in Rhesus Monkeys (Macaca mulatta)

    Cynthia M. Lester McCully; Bacher, John; MacAllister, Rhonda P; Steffen-Smith, Emilie A.; Saleem, Kadharbatcha; Thomas, Marvin L.; Cruz, Rafael; Warren, Katherine E.


    Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample...

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

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


    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 ...

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

    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.


    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: ...

  7. Intrathecal radiogold prophylaxis and findings of the cerebrospinal fluid in children suffering from acute lymphoblastic leukemia

    Intrathecal radiogold application represents an alternative to the prophylaxis of meningosis in childhood acute lymphoblastic leukemia. Its compatibility is good, there are rarely any clinical side effects. In addition to inconstant phagocytosis, changes of the protein value and its fractions could be identified in the cerebrospinal fluid. The cumulative rates of remission and survival are less marked in these groups of patients than in those who received a prophylactic skull irradiation. (author)

  8. Changes in cerebral artery blood flow velocity after intermittent cerebrospinal fluid drainage.

    Kempley, S T; Gamsu, H R


    Doppler ultrasound was used to measure blood flow velocity in the anterior cerebral artery of six premature infants with posthaemorrhagic hydrocephalus, before and after intermittent cerebrospinal fluid (CSF) drainage, on 23 occasions. There was a significant increase in mean blood flow velocity after the drainage procedures (+5.6 cm/s, 95% confidence interval +2.9 to +8.3 cm/s), which was accompanied by a decrease in velocity waveform pulsatility. CSF pressure also fell significantly. In pat...

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

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


    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...

  10. Metabolomic Analysis of Cerebrospinal Fluid Indicates Iron Deficiency Compromises Cerebral Energy Metabolism in the Infant Monkey

    Rao, Raghavendra; Ennis, Kathleen; Oz, Gulin; Lubach, Gabriele R.; Georgieff, Michael K.; Coe, Christopher L.


    Iron deficiency anemia affects many pregnant women and young infants worldwide. The health impact is significant, given iron’s known role in many body functions, including oxidative and lipid metabolism, protein synthesis and brain neurochemistry. The following research determined if 1H NMR spectroscopy-based metabolomic analysis of cerebrospinal fluid (CSF) could detect the adverse influence of early life iron deficiency on the central nervous system. Using a controlled dietary model in 43 i...

  11. Effects of Various Handling and Storage Conditions on Stability of Treponema pallidum DNA in Cerebrospinal Fluid

    Villanueva, A. V.; Podzorski, R. P.; Reyes, M. P.


    Treponema pallidum DNA from even small numbers of organisms was detectable in cerebrospinal fluid (CSF) stored at room temperature or at 4°C for several hours and in CSF subjected to three freeze-thaw cycles. These results suggest that negative PCR results for T. pallidum from patients diagnosed with T. pallidum invasion of the central nervous system are probably not due to the loss of target DNA prior to testing.

  12. Detection of posture-induced constriction of the cervical cerebrospinal fluid space by scintiscanning

    Scintiscanning of the cervical cerebrospinal fluid space at maximum ante- and retroflexion in 24 patients revealed the method to be recommended for use in the case of cervical myelopathy when the polymorphous early symptoms appear and before myelography as well as for follow-up examination. The detection of posture-induced constriction of the lumen provides additional information and increases the sensitivity considerably because, particularly during retroflexion, minor inflammatory reactions lead to scintigraphically detectable reduction in the liquor space. (author)

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

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


    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...

  14. Instability of cerebrospinal fluid after delayed storage and repeated freezing: a holistic study by drop coating deposition Raman spectroscopy

    Klener, J.; Hofbauerová, Kateřina; Bartoš, A.; Říčný, J.; Řípová, D.; Kopecký, V. Jr.


    Roč. 52, č. 5 (2014), s. 657-664. ISSN 1434-6621 Institutional support: RVO:61388971 Keywords : Alzheimer's disease * cerebrospinal fluid * cold denaturation Subject RIV: EC - Immunology Impact factor: 2.707, year: 2014

  15. Relationship between platelet MAO activity and concentrations of 5-HIAA and HVA in cerebrospinal fluid in chronic pain patients

    Platelet monoamine oxidase (MAO) activity and concentrations of 5-HIAA and HVA in the cerebrospinal fluid (CSF) were estimated in a series of 54 chronic pain patients. Platelet MAO activity was found to correlate, positively to CSF concentrations of 5-HIAA and HVA, which had been adjusted in order to eliminate the influence of age and body height. However, only the correlation with 5-HIAA reached a significant level. When partial correlations were sought, only the positive correlation between platelet MAO activity and CSF 5-HIAA remained. The results support the notion that platelet MAO is a biological marker for some trait dependent property of the central serotonergic system. (Author)

  16. Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF and plasma ? method-comparison evaluations

    Sérgio Monteiro de Almeida


    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.

  17. Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

    Tisell Magnus


    Full Text Available Abstract Background The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF induced by shunt surgery and the relationship between these changes and clinical improvement. Methods We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17 and idiopathic NPH (INPH, n = 18 before and 3 months after shunt surgery. Patients were divided into groups according to whether or not there was improvement in clinical symptoms after surgery. Results Preoperatively, the only pathological findings were elevated neurofilament protein (NFL, significantly more so in the SNPH patients than in the INPH patients, and elevated albumin content. Higher levels of NFL correlated with worse gait, balance, wakefulness and neuropsychological performance. Preoperatively, no differences were seen in any of the CSF biomarkers between patients that improved after surgery and those that did not improve. Postoperatively, a greater improvement in gait and balance performance correlated with a more pronounced reduction in NFL. Levels of albumin, albumin ratio, neuropeptide Y, vasoactive intestinal peptide and ganglioside GD3 increased significantly after shunting in both groups. In addition, Gamma amino butyric acid increased significantly in SNPH and tau in INPH. Conclusion We conclude that a number of biochemical changes occur after shunt surgery, but there are no marked differences between the SNPH and INPH patients. The results indicate that NFL may be a marker that can predict a surgically reversible state in NPH.

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

    Selaković Vesna M.


    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.

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

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


    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

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

    Šimić, Goran; Boban, Marina; Patrick R Hof


    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...

  1. Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid.

    Young, S N; Gauthier, S.


    Tryptophan 5-hydroxyindoleacetic acid and indoleacetic acid were measured in cerebrospinal fluid taken during pneumoencephalography from patients, some of whom took a 3 g or 6 g tryptophan load at various times before. Measurements were made on both lumbar and cisternal cerebrospinal fluid and the results showed similarities between indoleamine metabolism in human brain and spinal cord. Our data suggested that (1) the blood-brain barrier active transport system for tryptophan is not far from ...

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

    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


    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

  3. Cerebrospinal fluid leakage. Indications, technique and results of treatment with a blood patch

    In most cases cerebrospinal fluid (CSF) leaks are iatrogenic and caused by medical interventions, such as lumbar puncture, peridural anesthesia and surgical interventions on the spine, However, spontaneous cerebral hypotension is currently detected more frequently due to improvements in diagnostic possibilities but often the cause cannot be clarified with certainty. There are various diagnostic tools for confirming the diagnosis and searching for the site of CSF leakage, such as postmyelography computed tomography (postmyelo-CT), indium111 radioisotope cisternography and (myelo) magnetic resonance imaging (MRI), which show different sensitivities. In accordance with own experience native MRI with fat-saturated T2-weighted sequences is often sufficient for diagnosing CSF leakage and the site. For the remaining cases an additional postmyelo-CT or alternatively myelo-MRI is recommended. In some patients with spontaneous cranial hypotension multiple CSF leaks are found at different spinal levels. The main symptom in most cases is an orthostatic headache. While post-puncture syndrome is self-limiting in many cases, spontaneous CSF leakage usually requires blood patch therapy. A lumbar blood patch can be safely carried out under guidance by fluoroscopy. In the case of a cervical or dorsal blood patch, CT guidance is recommended, which ensures epidural application of the blood patch and minimizes the risk of damaging the spinal cord. Despite a high success rate at the first attempt with a blood patch of up to 85 %, some cases require repeating the blood patch. A targeted blood patch of a CSF leak should generally be favoured over a blindly placed blood patch; nevertheless, if a CSF leak cannot be localized by CT or MRI a therapeutic attempt with a lumbar blood patch can be carried out. After a successful blood patch intracranial hygromas and pachymeningeal enhancement in the head show fast regression; however, epidural hygromas of the spine can persist for a period of

  4. Prion-seeding activity in cerebrospinal fluid of deer with chronic wasting disease.

    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

  5. Coupling poroelasticity and CFD for cerebrospinal fluid hydrodynamics.

    Tully, Brett; Ventikos, Yiannis


    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

  6. Cytokines in cerebrospinal fluid of neurosyphilis patients: Identification of Urokinase plasminogen activator using antibody microarrays.

    Lu, Ping; Zheng, Dao-Cheng; Fang, Chang; Huang, Jin-Mei; Ke, Wu-Jian; Wang, Liu-Yuan; Zeng, Wei-Ying; Zheng, He-Ping; Yang, Bin


    Little is known regarding protein responses to syphilis infection in cerebrospinal fluid (CSF) of patients presenting with neurosyphilis. Protein and antibody arrays offer a new opportunity to gain insights into global protein expression profiles in these patients. Here we obtained CSF samples from 46 syphilis patients, 25 of which diagnosed as having central nervous system involvement based on clinical and laboratory findings. The CSF samples were then analyzed using a RayBioH L-Series 507 Antibody Array system designed to simultaneously analyze 507 specific cytokines. The results indicated that 41 molecules showed higher levels in patients with neurosyphilis in comparison with patients without neural involvement. For validation by single target ELISA, we selected five of them (MIP-1a, I-TAC/CXCL11, Urokinase plasminogen activator [uPA], and Oncostatin M) because they have previously been found to be involved in central nervous system (CNS) disorders. The ELISA tests confirmed that uPA levels were significantly higher in the CSF of neurosyphilis patients (109.1±7.88pg/ml) versus patients without CNS involvement (63.86±4.53pg/ml, p<0.0001). There was also a clear correlation between CSF uPA levels and CSF protein levels (p=0.0128) as well as CSF-VDRL titers (p=0.0074) used to diagnose neurosyphilis. No significant difference between the two groups of patients, however, was found in uPA levels in the serum, suggesting specific activation of the inflammatory system in the CNS but not the periphery in neurosyphilis patients. We conclude that measurements of uPA levels in CSF may be an additional parameter for diagnosing neurosyphilis. PMID:27049560

  7. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

    Veening Jan G


    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.

  8. ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

    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

  9. [A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

    Arita, Yuki; Tono, Toshihiro; Hosoda, Tomohiro; Taguchi, Hiroaki; Sakamoto, Mitsuo; Osone, Yasuo; Nozaki, Hiroyuki


    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

  10. Methodological aspects of ELISA analysis of thioredoxin 1 in human plasma and cerebrospinal fluid.

    Lundberg, Mathias; Curbo, Sophie; Reiser, Kathrin; Masterman, Thomas; Braesch-Andersen, Sten; Areström, Irene; Ahlborg, Niklas


    Thioredoxin-1 (Trx1) is a protein antioxidant involved in major cellular processes. Increased plasma levels of Trx1 have been associated with human diseases suggesting that Trx1 is a marker for oxidative stress with putative clinical use. However, the reported mean levels of Trx1 in the control cohorts vary a hundred-fold between studies (0.8-87 ng/ml), possibly due to methodological differences between the capture ELISA used in the different studies. The aim of this study was to investigate methodological aspects related to the ELISA measurement of Trx1. ELISAs utilizing different capture and detection combinations of antibodies to Trx1 and as well as recombinant human (rh) Trx1 standards from two sources were characterized. The different ELISAs were subsequently used to measure Trx1 in human plasma and cerebrospinal fluid samples (CSF) from healthy donors and from patients with various neurological diagnoses. The Trx1 standards differed in their content of monomeric and oligomeric Trx1, which affected the ELISAs composed of different antibody combinations. Thus, the levels of Trx1 determined in human plasma and CSF samples varied depending on the antibody used in the ELISAs and on the rhTrx1 standard. Furthermore, the relevance of preventing interference by heterophilic antibodies (HA) in human plasma and CSF was investigated. The addition of a HA blocking buffer to human samples drastically reduced the ELISA signals in many samples showing that HA are likely to cause false positive results unless they are blocked. In conclusion, the study shows that the design of a Trx1 ELISA in regards to antibodies and standards used has an impact on the measured Trx1 levels. Importantly, analyses of human plasma and CSF without preventing HA interference may obscure the obtained data. Overall, the results of this study are crucial for the improvement of future studies on the association of Trx1 levels with various diseases. PMID:25075746

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

    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

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

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


    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.

  13. Serum and cerebrospinal fluid concentrations of E-selectin in patients with aneurysmal subarachnoid hemorrhage

    T. Tanriverdi


    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.

  14. Beta-2-transferrin to detect cerebrospinal fluid pleural effusion: a case report

    Smith Jennifer C


    Full Text Available Abstract Introduction Pleural effusion secondary to ventriculoperitoneal shunt insertion is a rare and potentially life-threatening occurrence. Case presentation We describe a 14-month-old Caucasian boy who had a ventriculoperitoneal shunt inserted for progressive hydrocephalus of unknown etiology. Two and a half months post-shunt insertion, the patient presented with mild respiratory distress. A chest radiograph revealed a large right pleural effusion and a shunt series demonstrated an appropriately placed distal catheter tip. A subsequent abdominal ultrasound revealed marked ascites. Fluid drained via tube thoracostomy was sent for beta-2-transferrin electrophoresis. A positive test was highly suggestive of cerebral spinal fluid hydrothorax. Post-externalization of the ventriculoperitoneal shunt, the ascites and pleural effusion resolved. Conclusion Testing for beta-2-transferrin protein in pleural fluid may serve as a useful technique for diagnosing cerebrospinal fluid hydrothorax in patients with ventriculoperitoneal shunts.

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

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


    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......, 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...

  16. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy.

    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


    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

  17. Impact of cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus on the amyloid cascade.

    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.

  18. Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection

    Bremell Daniel


    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.

  19. Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

    M.A. Moreira


    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05. CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL than in controls (237.1 ± 16.4 pg/mL, P < 0.01. There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

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

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


    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

  1. Monochloroacetic acid lethality in the rat in relation to lactic acid accumulation in the cerebrospinal fluid

    Potential antidotes for human exposure to monochloroacetic acid (MCA) were evaluated using a rodent model. Dichloroacetic acid (DCA) and phenobarbital (PB) but not ethanol or phenytoin, were found to be effective antidotes to monochloroacetic acid (MCA) in rats. DCA (110 mg/kg, ip), administered to rats 15 minutes after a LD-80 of MCA (80 mg/kg, iv), consistently reduced mortality to 0%, while PB reduced mortality to less than 20%. Both DCA and PB were found to be similarly effective in mice. The hypothesis that PB reduces mortality in MCA treated rats by altering the metabolic disposition of MCA was evaluated and rejected. Administration of PB to rats treated with a lethal dose of [14C]MCA did not alter the concentrations of MCA or its metabolites in plasma or cerebrospinal fluid (CSF), or the extent of covalent binding between radioactivity equivalent to [14C]MCA and brain proteins. The relationship between altered blood-brain barrier permeability and death in MCA treated rats was investigated. Treatment with MCA (80 mg/kg, iv) was associated with a significant (50%) increase in the permeability of the rat blood-brain barrier to [125I]BSA. The effect was not altered by treatment with PB, however, suggesting that altered blood-brain barrier permeability does not have an important role in the lethal effect of MCA in rats. The effect of MCA on brain carbohydrate metabolism in vivo was investigated. CSF and blood lactic acid concentrations increased in MCA treated rats, and the increase in CSF levels was dose related. In individual MCA treated rats, CSF lactate concentrations paralleled the time course of ataxia and a discrete threshold for death (18 mmol/L) was observed. The relationship between excess brain lactate levels and death in MCA treated rats was investigated further

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

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


    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

  3. Lack of KIs virus DNA in plasma and cerebrospinal fluid in Italy.

    Macera, Lisa; Focosi, Daniele; Manzin, Aldo; Ceccherini Nelli, Luca; Pistello, Mauro; Maggi, Fabrizio


    Dear Sirs, Satoh et al. recently screened 516 Japanese blood donors with PCR using primers constructed from the consensus domain of the helicase of positive-stranded RNA viruses. They reported a novel enveloped virus with a circular double-stranded DNA genome (tentatively named KIs virus, KIs-V) (Satoh et al., 2011) occurring in 36 out of the 100 hepatitis E (HEV) antibody-positive donors with elevated alanine aminotransferase (ALT) levels (>60 IU/L). More recently, Biagini et al. failed to find KIs-V in plasma from 576 French blood donors with unknown HEV serostatus and unknown ALT values (Biagini et al., 2012). Based on an HEV seroprevalence of 3-52% in France, the authors suggested an uncommon frequency of KIs-V infection in healthy persons in France. To date, no information has been available on the prevalence of KIs-V DNA in Italy. In the present paper, we analyzed KIs-V in 242 plasma samples of blood donors, transplant recipients, and patients with chronic viral infections, and in 52 cerebrospinal fluid (CSF) samples of patients with different neurological disorders. Informed consent was obtained from all patients and the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its amendments. Viral DNA extraction was carried out on 200 μl of plasma or 200 μl of CSF by using QIAamp DNA blood kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Extracted nucleic acids were amplified for KIs-V DNA with the nested PCR protocol developed by Satoh et al. (2011) and used for screening Japanese blood donors. The first and second PCR rounds were designed on 458 and 304 nt-length fragments, respectively. To validate the amplification process, positive controls obtained from plasma dilutions of a synthetic template corresponding to the target sequence were run in each PCR. PCR sensitivity was less than 5 copies of target sequence. Fourteen liver and 16 kidney and/or pancreas transplant

  4. Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and [14C]methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption

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

    Bäckryd, Emmanuel


    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...


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


    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...

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

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


    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...... patients with type 2 diabetes (mean (range)): age 63 (54-79) years; actual body weight: 90 (75-118) kg treated with 1.8 mg liraglutide for 14 (5-22) months and with a treatment-induced weight loss of 8.4 (7-11) kg. We measured liraglutide in plasma and CSF with a radioimmunoassay specific for the N...

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

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


    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...

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

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


    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

  10. The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates

    Fox, Elizabeth; Jayaprakash, Nalini; Pham, Tuyet-Hang; Rowley, Ayana; McCully, Cynthia L; Pucino, Frank; Goldbach-Mansky, Raphaela


    Anakinra improves the central nervous system manifestations of neonatal-onset multisystem inflammatory disease, which is mediated by IL-1β oversecretion. The cerebrospinal fluid (CSF) penetration of the IL-1 receptor antagonist anakinra was studied in rhesus monkeys after intravenous doses of 3 and 10 mg/kg. Drug exposure (area under concentration-time curve) in CSF was 0.28% of that in serum. The average CSF concentration at 3 mg/kg was 1.8 ng/mL, which is 30-fold higher than endogenous CSF ...