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Sample records for cerebrospinal fluid monoamine

  1. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats.

    Science.gov (United States)

    van der Vegt, Bea J; Lieuwes, Natasja; Cremers, Thomas I F H; de Boer, Sietse F; Koolhaas, Jaap M

    2003-09-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has not been confirmed in rodents so far, while manipulation studies aimed to investigate the link between 5-HT and aggressive behaviour are mostly carried out in rodents. In this study the relation between aggression and CSF monoamine and metabolite concentrations was investigated in male Wildtype Groningen rats. In sharp contrast to the hypothesis and our expectation, a clear positive correlation was found between the individual level of trait-like aggressiveness and CSF concentrations of 5-HT, 5-HIAA, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC). Shortly after the acute display of aggressive behaviour (as a state-like phenomenon), decreased 5-HT levels and an increase in 5-HIAA/5-HT ratio and NE concentrations were found. Surprisingly, pharmacological challenges known to influence 5-HT transmission and aggressive behaviour did not affect CSF 5-HT and 5-HIAA concentrations, only the NE level was increased. Lesioning 5-HT terminals by 5,7-dihydroxytryptamine (5,7-DHT) administration caused a decrease in CSF 5-HT and 5-HIAA, but without affecting aggressive behaviour. The observed positive correlation between CSF 5-HIAA and trait aggressiveness makes it questionable whether a direct extrapolation of neurobiological mechanisms of aggression between species is justified. Interpretation of CSF metabolite levels in terms of activity of neural substrates requires a far more detailed knowledge of the dynamics and kinetics of a neurotransmitter after its release.

  2. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats.

    NARCIS (Netherlands)

    Vegt, B.J. van der; Lieuwes, N.G.; Cremers, T.I.; Boer, S.F. de; Koolhaas, J.M.

    2003-01-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has

  3. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats

    NARCIS (Netherlands)

    Vegt, Bea J. van der; Lieuwes, Natasja; Cremers, Thomas I.F.H.; Boer, Sietse F. de; Koolhaas, J.M.

    2003-01-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has

  4. Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4).

    Science.gov (United States)

    Usui, Takuya; Nakazawa, Ayumi; Okura, Takashi; Deguchi, Yoshiharu; Akanuma, Shin-Ichi; Kubo, Yoshiyuki; Hosoya, Ken-Ichi

    2016-11-01

    The elimination of histamine, an excitatory neurotransmitter, from the brain/CSF across the blood-brain barrier and blood-CSF barrier (BCSFB) was investigated using Wistar rats, which were anesthetized with pentobarbital sodium. An in vivo intracerebral microinjection study suggested that there was only partial efflux of [ 3 H]histamine from the rat brain across the blood-brain barrier. The [ 3 H]histamine elimination clearance from the rat CSF was 3.8-fold greater than that of a CSF bulk flow marker, and the elimination of [ 3 H]histamine was significantly inhibited by the co-administration of unlabeled histamine, suggesting the involvement of a carrier-mediated process in histamine elimination from the CSF. The uptake study of [ 3 H]histamine by the isolated rat choroid plexus revealed histamine elimination from the CSF across the BCSFB. The [ 3 H]histamine uptake by TR-CSFB3 cells, a model cell line for the BCSFB, exhibited temperature-dependent and saturable kinetics, suggesting the involvement of carrier-mediated transport of histamine at the BCSFB. In the inhibition study, [ 3 H]histamine uptake by TR-CSFB3 cells was significantly inhibited by substrates and/or inhibitors of plasma membrane monoamine transporter (PMAT/SLC29A4), but not affected by substrates of organic cation transporters. These results suggest the elimination of histamine from the CSF via plasma membrane monoamine transporter at the BCSFB. © 2016 International Society for Neurochemistry.

  5. Cerebrospinal fluid probenecid studies: a reinterpretation.

    Science.gov (United States)

    Cowdry, R W; Ebert, M H; van Kammen, D P; Post, R M; Goodwin, F K

    1983-11-01

    Probenecid is used to block the transport of acid monoamine metabolites from cerebrospinal fluid (CSF), on the assumption that the resultant rise in CSF concentrations of the metabolites will reflect presynaptic "turnover" of the parent monoamine. However, CSF levels of probenecid correlate with CSF levels of the metabolite, suggesting that the blockade is incomplete at the probenecid levels obtained in human studies. This article reviews the literature on CSF probenecid-metabolite correlations and presents data demonstrating variations in the correlations across diagnostic groups. These cross-diagnostic variations may be due to group differences in membrane transport characteristics and and confound attempts to "correct for" CSF probenecid concentrations in studies of monoamine turnover.

  6. Immunoglobulins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup

    2015-01-01

    The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion...

  7. Protein profiling of cerebrospinal fluid

    DEFF Research Database (Denmark)

    Simonsen, Anja H

    2012-01-01

    The cerebrospinal fluid (CSF) perfuses the brain and spinal cord. CSF contains proteins and peptides important for brain physiology and potentially also relevant for brain pathology. Hence, CSF is the perfect source to search for new biomarkers to improve diagnosis of neurological diseases as well...

  8. Simulation of cerebrospinal fluid transport

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

  9. Scintigraphy of the cerebrospinal fluid

    International Nuclear Information System (INIS)

    Touya, E.; Perillo, W.; Paez, A.; Osorio, A.; Ferrando, R.; Lago, G.; Garcia Guelfi, A.; Ferrari, M.

    1977-01-01

    Eight years of experience in scintigraphy of cerebrospinal fluid (CSF) with 113 Insup(m)-colloid is reported. Two hundred cases are discussed. On the basis of the clinical diagnosis, the cases are divided into five groups: (1) spinal cord compression; (2) hydrocephalus of the adult and child; (3) control of extracranial CSF shunts; (4) CSF fistula; and (5) brain tumour. It is concluded that the radiopharmaceutical used has no limitations except in the study of the hydrocephalus of the adult. For those services remote from the production centres, it is a convenient option for CSF scintigraphy. (author)

  10. Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

    NARCIS (Netherlands)

    Luykx, Jurjen J.; Bakker, Steven C.; Lentjes, Eef; Boks, Marco P. M.; van Geloven, Nan; Eijkemans, Marinus J. C.; Janson, Esther; Strengman, Eric; de Lepper, Anne M.; Westenberg, Herman; Klopper, Kai E.; Hoorn, Hendrik J.; Gelissen, Harry P. M. M.; Jordan, Julian; Tolenaar, Noortje M.; van Dongen, Eric P. A.; Michel, Bregt; Abramovic, Lucija; Horvath, Steve; Kappen, Teus; Bruins, Peter; Keijzers, Peter; Borgdorff, Paul; Ophoff, Roel A.; Kahn, René S.

    2012-01-01

    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

  11. Endoscopic repair of cerebrospinal fluid rhinorrhea.

    Science.gov (United States)

    Kljajić, Vladimir; Vuleković, Petar; Vlaški, Ljiljana; Savović, Slobodan; Dragičević, Danijela; Papić, Vladimir

    Nasal liquorrhea indicates a cerebrospinal fluid fistula, an open communication between the intracranial cerebrospinal fluid and the nasal cavity. It can be traumatic and spontaneous. The aim of this study was to assess the outcome of endoscopic repair of cerebrospinal fluid fistula using fluorescein. This retrospective study included 30 patients of both sexes, with a mean age of 48.7 years, treated in the period from 2007 to 2015. All patients underwent lumbar administration of 5% sodium fluorescein solution preoperatively. Fistula was closed using three-layer graft and fibrin glue. Cerebrospinal fluid fistulas were commonly located in the ethmoid (37%) and sphenoid sinus (33%). Most patients presented with traumatic cerebrospinal fluid fistulas (2/3 of patients). The reported success rate for the first repair attempt was 97%. Complications occurred in three patients: one patient presented with acute hydrocephalus, one with reversible encephalopathy syndrome on the fifth postoperative day with bilateral loss of vision, and one patient was diagnosed with hydrocephalus two years after the repair of cerebrospinal fluid fistula. Endoscopic diagnosis and repair of cerebrospinal fluid fistulas using fluorescein intrathecally has high success rate and low complication rate. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  12. Cerebrospinal fluid and ependymal neurophysin.

    Science.gov (United States)

    Robinson, A G; Zimmerman, E A

    1973-05-01

    Neurophysins are "carrier proteins" associated with vasopressin and oxytocin in the neurohypophyseal system. The release of these hormone associated proteins may serve as an indicator of posterior pituitary function. This report describes the measurement of neurophysin in human and monkey plasma and cerebrospinal fluid (CSF) by radioimmunoassay. Tissue neurophysin is also localized in monkey brain by the immunoperoxidase technique. CSF from 68 patients and five monkeys had easily measurable neurophysin in every sample. The concentration of neurophysin in CSF and in plasma of man is 5.4+/-0.30 ng/ml (mean and SEM) and 0.69+/-0.04, respectively. The two means were significantly different (P dogs did not enter CSF. Using the immunoperoxidase technique, we found neurophysin not only in the supraoptic and paraventricular nuclei, their tracts, and the posterior pituitary, but also in the specialized ependymal tanycytes of the infundibular recess of the third ventricle and in the external layer of the median eminence where capillaries drain into hypophyseal portal vessels. Neurophysin may pass from CSF to portal vessels via tanycytes in a manner similar to that postulated for releasing factors.

  13. Cerebrospinal fluid circulation and hydrocephalus.

    Science.gov (United States)

    Leinonen, Ville; Vanninen, Ritva; Rauramaa, Tuomas

    2017-01-01

    Hydrocephalus (HC) is classically defined as dynamic imbalance between the production and absorption of cerebrospinal fluid (CSF) leading to enlarged ventricles. Potential causative factors include various brain disorders like tumors causing obstruction of CSF flow within the ventricular system or the subarachnoid space. Classification of HC is based on the site of CSF flow obstruction guiding optimal treatment, with endoscopic third ventriculostomy in intraventricular obstruction and CSF shunt in communicating HC. Another clinically relevant classification is acute and chronic; the most frequent chronic form is idiopathic normal-pressure hydrocephalus (iNPH). The reported incidence of HC varies according to the study population and classification used. The incidence of congenital HC is approximately 0.4-0.6/1,000 newborns and the annual incidence of iNPH varies from 0.5/100,000 to 5.5/100,000. Radiologically, ventricular dilatation may be nonspecific, and differentiation of iNPH from other neurodegenerative diseases may be ambiguous. There are no known specific microscopic findings of HC but a systematic neuropathologic examination is needed to detect comorbid diseases and possible etiologic factors of HC. Depending on the etiology of HC, there are several nonspecific signs potentially to be seen. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Tissue polypeptide antigen activity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Bach, F; Söletormos, Georg; Dombernowsky, P

    1991-01-01

    Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis...

  15. The Maze of the Cerebrospinal Fluid Discovery

    Directory of Open Access Journals (Sweden)

    Leszek Herbowski

    2013-01-01

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

  16. The Maze of the Cerebrospinal Fluid Discovery

    OpenAIRE

    Herbowski, Leszek

    2013-01-01

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

  17. Substance P in human cerebrospinal fluid

    International Nuclear Information System (INIS)

    Wallasch, T.M.

    1987-01-01

    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) [de

  18. T 2 mapping of cerebrospinal fluid

    DEFF Research Database (Denmark)

    Spijkerman, Jolanda M; Petersen, Esben T; Hendrikse, Jeroen

    2018-01-01

    OBJECT: Cerebrospinal fluid (CSF) T 2 mapping can potentially be used to investigate CSF composition. A previously proposed CSF T 2-mapping method reported a T 2 difference between peripheral and ventricular CSF, and suggested that this reflected different CSF compositions. We studied...

  19. Cerebrospinal fluid markers of Alzheimer's disease

    NARCIS (Netherlands)

    van Gool, W. A.; Bolhuis, P. A.

    1991-01-01

    OBJECTIVE: To review studies on cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) in order to answer the question whether CSF contains a specific marker which can be used to support a clinical diagnosis of AD. DATA SOURCES: Studies identified through an English-language literature

  20. CEREBROSPINAL FLUID LACTATE IN MENINGITIS IN CHILDREN

    OpenAIRE

    Bindu Krishnan Padma; Deepa Kunju Krishnan

    2017-01-01

    BACKGROUND Meningitis is an inflammation of meninges and subarachnoid space and is often associated with cerebritis. Acute bacterial meningitis is one of the most common serious infections in children. Viral meningitis has a much more favourable prognosis. Cerebrospinal fluid analysis has got an important role in the diagnosis of neurological disorders. CSF lactate can be elevated in disorders like subarachnoid haemorrhage, bacterial meningitis, status epilepticus and inborn error...

  1. Cerebrospinal fluid leak mimicking allergic rhinitis.

    Science.gov (United States)

    Ricketti, Anthony J; Cleri, Dennis J; Porwancher, Richard B; Panesar, Mandip; Villota, Francisco J; Seelagy, Marc M

    2005-01-01

    Rhinitis and rhinorrhea are common clinical complaints that may be allergic or nonallergic in etiology. Distinguishing between allergic and nonallergic etiologies can be difficult but necessary for treatment. Here, we present a case of a 50-year-old woman with > 20 years of rhinorrhea before a diagnosis of cerebrospinal fluid leak and a life-threatening complication occurred. It is essential that no symptom, especially that which persists and resists treatment, is trivialized. Here, we establish how a careful history and evaluation will direct the clinician to the correct diagnosis.

  2. Cerebrospinal fluid oto- and rhinorrhoea, diagnosis and treatment

    International Nuclear Information System (INIS)

    Elverland, H.H.; Henning, R.; Lettrem, I.; Anke, I.M.; Ulvestad, E.

    1996-01-01

    Leakage of cerebrospinal fluid may occur after fracture of the skull base or after surgery on the skull base, nose, or paranasal sinuses. Further causes of cerebrospinal fluid leakage are tumours and malformations. It may also occur spontaneously. The authors describe four case reports illustrating diagnostic and surgical problems. Cerebrospinal fluid oto- and rhinorrhoea should be suspected in cases of recurring purulent meningitis. Immunologic demonstration of β 2 -transferrin in secretions from the nose and ear is a diagnostic sign of cerebrospinal fluid or perilymph. Digital subtraction cisternography, CT cisternography, and flowsensitive magnetic resonance imaging are sensitive methods for localizing dural leakage. Frontal craniotomy has been the traditional surgical approach. The recent evolvement of transnasal endoscopic sinus surgery and microsurgery has made it possible to treat cerebrospinal fluid oto- and rhinorrhoea with a high degree of success and less operative morbidity. 22 refs., 3 figs

  3. Imhotep and the Discovery of Cerebrospinal Fluid

    Science.gov (United States)

    Blomstedt, Patric

    2014-01-01

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

  4. Imhotep and the Discovery of Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Patric Blomstedt

    2014-01-01

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

  5. Spontaneous canine hydrocephalus: cerebrospinal fluid dynamics1

    Science.gov (United States)

    Sahar, A.; Hochwald, G. M.; Kay, W. J.; Ransohoff, J.

    1971-01-01

    Cerebrospinal fluid dynamics were studied in 14 dogs with spontaneous hydrocephalus. In nine of the dogs aqueductal obstruction was observed and the remainder had a `communicating type' hydrocephalus. The major histological findings consisted of severe ependymal destruction, spongy changes in the periventricular white matter, increased density of capillaries in this area, and varying degrees of thickening, fibrosis, and fusion of the choroid villi. The formation and absorption of CSF were studied by perfusion of the cerebral ventricles. The rate of formation of CSF was found to decrease with perfusion pressure by Vf = 0·02595−0·00022 P ml./min (P = pressure in cm H2O). The absorption of spinal fluid was found to increase linearly with pressure by Va = 0·0165 + 0·00050 P. The various factors influencing the formation and absorption of the spinal fluid are discussed. The meaning and attainment of `arrest' of the hydrocephalic process in terms of the measured rates of CSF formation and absorption in these animals are considered. Images PMID:5571319

  6. Proteome analysis of chick embryonic cerebrospinal fluid.

    Science.gov (United States)

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

    2006-01-01

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

  7. Cerebrospinal fluid pleocytosis level as a diagnostic predictor?

    DEFF Research Database (Denmark)

    Østergaard, Anne Ahrens; Sydenham, Thomas Vognbjerg; Nybo, Mads

    2017-01-01

    /ml). We wanted to assess the diagnostic diversity of unselected adult patients with pleocytosis in the cerebrospinal fluid. METHODS: The study is based on data from cerebrospinal fluid (CSF) analyses of all adult patients (15 years or older) admitted to a large university hospital in Denmark during a two......-year period (2008-2009). Data from the local patient administrative system supplied with data from patient charts were combined with laboratory data. RESULTS: A total of 5390 cerebrospinal fluid samples from 3290 patients were included. Pleocytosis >5 leucocytes/μl was found in samples from 262 patients...

  8. Cerebrospinal fluid composition modifications after neuroendoscopic procedures.

    Science.gov (United States)

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

    2007-02-01

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

  9. Imaging review of cerebrospinal fluid leaks

    Directory of Open Access Journals (Sweden)

    Naga V Vemuri

    2017-01-01

    Full Text Available Cerebrospinal fluid (CSF leak occurs due to a defect in the dura and skull base. Trauma remains the most common cause of CSF leak; however, a significant number of cases are iatrogenic, and result from a complication of functional endoscopic sinus surgery (FESS. Early diagnosis of CSF leak is of paramount importance to prevent life-threatening complications such as brain abscess and meningitis. Imaging plays a crucial role in the detection and characterization of CSF leaks. Three-dimensional, isotropic, high resolution computed tomography (HRCT accurately detects the site and size of the bony defect. CT cisternography, though invasive, helps accurately identify the site of CSF leak, especially in the presence of multiple bony defects. Magnetic resonance imaging (MRI accurately detects CSF leaks and associated complications such as the encephaloceles and meningoceles. In this review, we emphasize the importance and usefulness of 3D T2 DRIVE MR cisternography in localizing CSF leaks. This sequence has the advantages of effective bone and fat suppression, decreased artefacts, faster acquisition times, three-dimensional capability, y and high spatial resolution in addition to providing very bright signal from the CSF.

  10. Cerebrospinal Fluid (CSF) Analysis: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... bacteria, and other substances in the cerebrospinal fluid Autoimmune disorders , such as Guillain-Barré Syndrome and multiple sclerosis ( ... the brain or spinal cord, or of an autoimmune disorder, such as multiple sclerosis (MS). Symptoms of a ...

  11. Cerebrospinal fluid pleocytosis level as a diagnostic predictor?

    DEFF Research Database (Denmark)

    Østergaard, Anne Ahrens; Sydenham, Thomas Vognbjerg; Nybo, Mads

    2017-01-01

    BACKGROUND: Lumbar puncture with quantification of leukocytes and differential count of cellular subsets in the cerebrospinal fluid is a standard procedure in cases of suspected neuroinfectious conditions. However, a number of non-infectious causes may result in a low leukocyte number (0-1000 cells....../ml). We wanted to assess the diagnostic diversity of unselected adult patients with pleocytosis in the cerebrospinal fluid. METHODS: The study is based on data from cerebrospinal fluid (CSF) analyses of all adult patients (15 years or older) admitted to a large university hospital in Denmark during a two......-year period (2008-2009). Data from the local patient administrative system supplied with data from patient charts were combined with laboratory data. RESULTS: A total of 5390 cerebrospinal fluid samples from 3290 patients were included. Pleocytosis >5 leucocytes/μl was found in samples from 262 patients...

  12. Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET

    DEFF Research Database (Denmark)

    De Leon, Mony J.; Li, Yi; Okamura, Nobuyuki

    2017-01-01

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribrif......Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing...

  13. Cerebrospinal fluid dynamics study in communicating hydrocephalus.

    Science.gov (United States)

    Ramesh, Vengalathur Ganesan; Narasimhan, Vidhya; Balasubramanian, Chandramouli

    2017-01-01

    Communicating hydrocephalus often poses a challenge in diagnosis and management decisions. The objective of this study is to measure the opening pressure (P o ), pressure volume index (PVI), and cerebrospinal fluid outflow resistance (R out ), in patients with communicating hydrocephalus using bolus lumbar injection method and to evaluate its diagnostic and prognostic value. The study was conducted in 50 patients with communicating hydrocephalus, including normal pressure hydrocephalus (NPH) (19), post-meningitic hydrocephalus (23) and post-traumatic hydrocephalus (8). An improvised bolus lumbar injection method [the Madras Institute of Neurology (MIN) method] was used. In the NPH Group, the CSF dynamics studies correlated well with the clinico-radiological classification. The prediction of shunt responsiveness by CSF dynamics studies correlated with good outcome in 87.5%. In the post-meningitic hydrocephalus group, the value of CSF dynamics studies in predicting patients needing shunt was 89.5%. The CSF dynamics studies detected patients who needed shunt earlier than clinical or radiological indications. In the post-traumatic hydrocephalus group, 62.5% of patients improved with the treatment based on CSF dynamics studies. The improvised bolus lumbar injection method (MIN method) is a very simple test with fairly reliable and reproducible results. Study of CSF dynamics is a valuable tool in communicating hydrocephalus for confirmation of diagnosis and predicting shunt responsiveness. This is the first time that the value of CSF dynamics has been studied in patients with post-meningitic hydrocephalus. It was also useful for early selection of cases for shunting and for identifying patients with atrophic ventriculomegaly, thereby avoiding unnecessary shunt.

  14. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

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

  15. Quantitative proteomics of delirium cerebrospinal fluid

    Science.gov (United States)

    Poljak, A; Hill, M; Hall, R J; MacLullich, A M; Raftery, M J; Tai, J; Yan, S; Caplan, G A

    2014-01-01

    Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis. PMID:25369144

  16. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus

    Science.gov (United States)

    Limbrick, David D.; Baksh, Brandon; Morgan, Clinton D.; Habiyaremye, Gakwaya; McAllister, James P.; Inder, Terrie E.; Mercer, Deanna; Holtzman, David M.; Strahle, Jennifer; Wallendorf, Michael J.; Morales, Diego M.

    2017-01-01

    Introduction Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC. Conclusions CSF proteins such as s

  17. The 1H NMR profile of healthy dog cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Mihai Musteata

    Full Text Available The availability of data for reference values in cerebrospinal fluid for healthy humans is limited due to obvious practical and ethical issues. The variability of reported values for metabolites in human cerebrospinal fluid is quite large. Dogs present great similarities with humans, including in cases of central nervous system pathologies. The paper presents the first study on healthy dog cerebrospinal fluid metabolomic profile using (1H NMR spectroscopy. A number of 13 metabolites have been identified and quantified from cerebrospinal fluid collected from a group of 10 mix breed healthy dogs. The biological variability as resulting from the relative standard deviation of the physiological concentrations of the identified metabolites had a mean of 18.20% (range between 9.3% and 44.8%. The reported concentrations for metabolites may be used as normal reference values. The homogeneity of the obtained results and the low biologic variability show that the (1H NMR analysis of the dog's cerebrospinal fluid is reliable in designing and interpreting clinical and therapeutic trials in dogs with central nervous system pathologies.

  18. MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage

    DEFF Research Database (Denmark)

    Bache, Søren; Rasmussen, Rune; Rossing, Maria

    2017-01-01

    BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid...... from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. METHODS: In a prospective case-control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened...... passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients (P

  19. Application of transport phenomena analysis technique to cerebrospinal fluid.

    Science.gov (United States)

    Lam, C H; Hansen, E A; Hall, W A; Hubel, A

    2013-12-01

    The study of hydrocephalus and the modeling of cerebrospinal fluid flow have proceeded in the past using mathematical analysis that was very capable of prediction phenomenonologically but not well in physiologic parameters. In this paper, the basis of fluid dynamics at the physiologic state is explained using first established equations of transport phenomenon. Then, microscopic and molecular level techniques of modeling are described using porous media theory and chemical kinetic theory and then applied to cerebrospinal fluid (CSF) dynamics. Using techniques of transport analysis allows the field of cerebrospinal fluid dynamics to approach the level of sophistication of urine and blood transport. Concepts such as intracellular and intercellular pathways, compartmentalization, and tortuosity are associated with quantifiable parameters that are relevant to the anatomy and physiology of cerebrospinal fluid transport. The engineering field of transport phenomenon is rich and steeped in architectural, aeronautical, nautical, and more recently biological history. This paper summarizes and reviews the approaches that have been taken in the field of engineering and applies it to CSF flow.

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

    Directory of Open Access Journals (Sweden)

    Haaland Øystein A

    2010-06-01

    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.

  1. analysis of the indications and results of cerebrospinal fluid ...

    African Journals Online (AJOL)

    Kilifi Hospital. Pneumoccocus and Salmonella species are the commonest causes of pyogenic meningitis. Strategies should be put in place to improve the rates of lumbar puncture at MNH and the isolation of bacterial pathogens from cerebrospinal fluid cultures in both hospitals. Other possible causes for meningitis such as ...

  2. Pathogenicity of bloodstream and cerebrospinal fluid forms of ...

    African Journals Online (AJOL)

    However, it is not clear whether bloodstream forms (BSF) of T.b.rhodesiense differ in biological characteristics from the cerebrospinal fluid (CSF) forms. The present study was carried out to compare the pathogenicity of CSF and BSF of T.b. rhodesiense parasites in Swiss white mice following intraperitoneal inoculation with ...

  3. Cerebrospinal fluid loss at lumbar puncture for caesarean section ...

    African Journals Online (AJOL)

    Background Post dural puncture headache (PDPH) is an unpleasant complication of spinal anaesthesia. Several studies have attempted explanation of its pathophysiology. A widely held view is that it results from loss of cerebrospinal fluid volume resulting from leak following a hole left in the dura after the puncture.

  4. Bacterial Isolates from Cerebrospinal Fluid (CSF) of Patients In a ...

    African Journals Online (AJOL)

    The presence of bacteria in cerebrospinal fluid (CSF) results in the inflammation of the meninges, a condition known as meningitis. The aim of the study is to determine the prevalence of bacteria, which causes meningitis and their susceptibility pattern. This study, which was prospective and cross sectional involved patients ...

  5. Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer's Disease in Clinical Practice

    DEFF Research Database (Denmark)

    Slats, Diane; Spies, Petra E; Sjögren, Magnus J C

    2010-01-01

    Analysis of the brain specific biomarkers amyloid beta(42) (Abeta(42)) and total tau (t-tau) protein in cerebrospinal fluid (CSF) has a sensitivity and specificity of more than 85% for differentiating Alzheimer's Disease (AD) from non-demented controls. International guidelines are contradictory...

  6. The usefulness of cerebrospinal fluid tests for neurosyphilis ...

    African Journals Online (AJOL)

    To determine the usefulness of cerebrospinal fluid (CSF) tests for syphilis at a large academic hospital, clinical and laboratory data on 644 patients in whom such testing was requested over a 12-month period were analysed. In 198 cases (31 %) the Treponema paJlidum haemagglutination (TPHA) screening test could not ...

  7. Cerebrospinal fluid ascites. a case report and literature review ...

    African Journals Online (AJOL)

    Cerebrospinal fluid ascites is one complication of ventriculoperitoneal shunt surgery. This case reports a 7year old child with abdominal distention five years after ventriculoperitoneal shunt insertion for hydrocephalus secondary to aqueductal stenosis. The child had a history of multiple shunt revisions. Liver, cardiac and ...

  8. Prediction of cerebrospinal fluid parameters for tuberculous meningitis.

    Science.gov (United States)

    Zou, Yueli; He, Junying; Guo, Li; Bu, Hui; Liu, Yajuan

    2015-09-01

    Tuberculous meningitis is the most lethal form of tuberculosis, but current diagnostic methods are inadequate. The measurement of cerebrospinal fluid parameters can provide early information for diagnosis. The present study focus on the validity of the cut-off value of cerebrospinal fluid parameters according to the Lancet consensus of scoring system for diagnosis of tuberculous meningitis. A total of 100 confirmed patients were enrolled in this study. We evaluated significance of protein level (>1 g/l), chloride level (50%), and neutrophil predominance (>50%) in early diagnosis of tuberculous meningitis. The cerebrospinal fluid parameters were significantly different between the tuberculous meningitis group and the control group. The independent factors for diagnosis of tuberculous meningitis were protein level (>1 g/l), glucose level (50%). Neutrophil predominance (>50%) performed the best with the area under the curve of 89.7%. The sensitivity of protein level (>1 g/l), glucose level (50%) for diagnosis of tuberculous meningitis were 66%, 58%, 86%, and 54%, and the specificity were 84%, 98%, 32%, and 98%. There are 84% patients in tuberculous meningitis group at least having two positive parameters among the four independent parameters, while only 10% in control group. The cerebrospinal fluid parameters can help the clinicians to make a prompt diagnosis in the early stage of the disease. © 2015 Wiley Periodicals, Inc.

  9. The usefulness of cerebrospinal fluid tests for neurosyphilis

    African Journals Online (AJOL)

    To determine the usefulness of cerebrospinal fluid (CSF) tests for syphilis at a large academic hospital, clinical and laboratory data on 644 patients in whom such testing was requested over a 12-month period were analysed. In 198 cases (31 %) the Treponema paJlidum haemagglutination. (TPHA) screening test could not ...

  10. Activity of daptomycin against Listeria monocytogenes isolates from cerebrospinal fluid

    NARCIS (Netherlands)

    Spanjaard, Lodewijk; Vandenbroucke-Grauls, Christina M. J. E.

    2008-01-01

    We tested the activity of daptomycin against 76 Listeria monocytogenes isolates from cerebrospinal fluid by broth dilution and Etest methods. For the broth dilution method, the MIC range was 1.0 to 8.0 and the MIC at which 90% of the isolates tested were inhibited (MIC(90)) was 4.0 mg/liter. For the

  11. Measles Antibodies in the Serum and Cerebrospinal Fluid in ...

    African Journals Online (AJOL)

    The levels of complement-fixing antibodies to measles antigen in the sera and cerebrospinal fluids of 17 patients with subacute sclerosing panencephalitis seen in a 2-year period, are compared with those in 14 measles patients with or without acute encephalitis and 25 patients with neurological disease.

  12. Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects

    NARCIS (Netherlands)

    Toledo, J.B.; Zetterberg, H.; van Harten, A.C.; Glodzik, L.; Martinez-Lage, P.; Bocchio-Chiavetto, L.; Rami, L.; Hansson, O.; Sperling, R.; Engelborghs, S.; Osorio, R.S.; Vanderstichele, H.; Vandijck, M.; Hampel, H.; Teipl, S.; Moghekar, A.; Albert, M.; Hu, W.T.; Argiles, J.A.M.; Gorostidi, A.; Teunissen, C.E.; de Deyn, P.P.; Hyman, B.T.; Molinuevo, J.L.; Frisoni, G. B.; Linazasoro, G.; de Leon, M.J.; van der Flier, W.M.; Scheltens, P.; Blennow, K.; Shaw, L.M.; Trojanowski, J.Q.

    2015-01-01

    In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from

  13. Cerebrospinal fluid cutaneous fistula following obstetric epidural analgaesia. Case report.

    Science.gov (United States)

    Fedriani de Matos, J J; Quintero Salvago, A V; Gómez Cortés, M D

    2017-10-01

    Cutaneous fistula of cerebrospinal fluid is a rare complication of neuroaxial blockade. We report the case of a parturient in whom an epidural catheter was placed for labour analgesia and 12h after the catheter was removed, presented an abundant asymptomatic fluid leak from the puncture site, compatible in the cyto-chemical analysis with cerebrospinal fluid. She was treated with acetazolamide, compression of skin orifice of the fluid leakage, antibiotic prophylaxis, hydration and rest, and progressed satisfactorily without requiring blood patch. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy

    NARCIS (Netherlands)

    Gisolf, E. H.; van Praag, R. M.; Jurriaans, S.; Portegies, P.; Goudsmit, J.; Danner, S. A.; Lange, J. M.; Prins, J. M.

    2000-01-01

    Only limited data on cerebrospinal fluid (CSF) HIV-1 RNA responses and markers of local inflammation in CSF during antiretroviral therapy are available. HIV-RNA, soluble tumor necrosis factor (TNF)-receptor (sTNFr)-II, monocyte chemoattractant protein (MCP)-1, and interferon-gamma-inducible protein

  15. Diagnosis and treatment of traumatic intracranial hypotension (cerebrospinal fluid hypovolemia)

    International Nuclear Information System (INIS)

    Shinonaga, Masamichi; Suzuki, Shinichi

    2003-01-01

    Patients who complain headache, neck pain, dizziness or vertigo, tinnitus, blurred vision, loss of concentration, memory disturbance and fatigue for over one year after mild head injury and whiplash injury are diagnosed as post-traumatic syndrome. Mechanism and treatment of post-traumatic syndrome are not well established. We studied radioisotope (RI) cisternography and enhanced brain magnetic resonance imaging (MRI) for the patient of post-traumatic syndrome. Of 175 cases in post-traumatic syndrome 141 cases (120 cases of motor vehicle accident, 21 cases of sports injury) were diagnosed, as intracranial hypotension (cerebrospinal fluid hypovolemia). RI cisternography showed 86% positive findings (early accumulation of RI in bladder and leakage). Prominent findings in MRI were dilatation of subdural space and venous dilatation. In every case epidural blood patch was performed and symptoms were improved in almost 70% of patients. This study revealed cerebrospinal fluid hypovolemia might be one cause of post-traumatic syndrome. (author)

  16. Utility of cerebrospinal fluid cortisol level in acute bacterial meningitis

    OpenAIRE

    Anish Mehta; Rohan R Mahale; Uchil Sudhir; Mahendra Javali; Rangasetty Srinivasa

    2015-01-01

    Background: Meningitis remains a serious clinical problem in developing as well as developed countries. Delay in diagnosis and treatment results in significant morbidity and mortality. The role and levels of intrathecal endogenous cortisol is not known. Objective: To study the cerebrospinal fluid (CSF) cortisol levels and to evaluate its role as a diagnostic and therapeutic marker in acute bacterial meningitis. Materials and Methods: Thirty patients with acute bacterial meningitis with no pri...

  17. Estimation of cerebrospinal fluid cortisol level in tuberculous meningitis

    OpenAIRE

    Rohan R Mahale; Anish Mehta; Sudhir Uchil

    2015-01-01

    Background: Central nervous system (CNS) involvement in tuberculosis is around 5?10%. Of the various manifestations of CNS tuberculosis, meningitis is the most common (70?80%). Delay in diagnosis and treatment results in significant morbidity and mortality. Objective: To study the cerebrospinal fluid (CSF) cortisol levels in tubercular meningitis and compare the levels with controls. Methods: Cross-sectional, prospective, observational, hospital-based study done in 20 patients of tubercular m...

  18. Adenosine deaminase organic effect in normal and abnormal cerebrospinal fluid

    International Nuclear Information System (INIS)

    Hamad, A.M.; Samarai, M.A.

    2007-01-01

    To study the effect of the organic substances on adenosine deaminase (ADA) activity in normal and abnormal cerebrospinal fluid (CSF). Various concentrations of 2-mercaptopurine, Ame-tycine, Adenosine analogues (Guanine, Thymine) and ATP were tested to see their effect on ADA activity in normal and abnormal CSF. ADA activity in normal and abnormal CSF was remarkably decreased with the increasing of concentrations of substances tested. These effects may have important therapeutic implications. (author)

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

    Directory of Open Access Journals (Sweden)

    Sandro Luiz de Andrade Matas

    2013-09-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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....

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

    Directory of Open Access Journals (Sweden)

    Anders Jens

    2001-12-01

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

  2. Heteromers of amyloid precursor protein in cerebrospinal fluid

    OpenAIRE

    Cuchillo-Iba?ez, Inmaculada; Lopez-Font, Inmaculada; Boix-Amor?s, Alba; Brinkmalm, Gunnar; Blennow, Kaj; Molinuevo, Jose-Luis; S?ez-Valero, Javier

    2015-01-01

    Background Soluble fragments of the amyloid precursor protein (APP) generated by ?- and ?-secretases, sAPP? and sAPP?, have been postulated as promising new cerebrospinal fluid (CSF) biomarkers for the clinical diagnosis of Alzheimer?s disease (AD). However, the capacity of these soluble proteins to assemble has not been explored and could be relevant. Our aim is to characterize possible sAPP oligomers that could contribute to the quantification of sAPP? and sAPP? in CSF by ELISA, as well as ...

  3. Detection of Mycobacterium tuberculosis in cerebrospinal fluid following immunomagnetic enrichment.

    Science.gov (United States)

    Mazurek, G H; Reddy, V; Murphy, D; Ansari, T

    1996-01-01

    The detection of Mycobacterium tuberculosis by culture of cerebrospinal fluid (CSF) is unacceptably slow. Low numbers of organisms and the presence of reaction inhibitors may prevent detection of M. tuberculosis by PCR. We used immunomagnetic enrichment to accelerate and enhance the detection of mycobacteria in CSF after demonstrating the utility of the method with pure suspensions. Growth was detected earlier in Bactec cultures of magnetically recovered mycobacteria than in untreated CSF (7 versus 15 days). We detected M. tuberculosis DNA by PCR in the immunomagnetically enriched sample but not in untreated CSF. PCR fingerprintings of the immunomagnetically recovered M. tuberculosis and of the isolate subsequently recovered by culture were identical. PMID:8789037

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

    International Nuclear Information System (INIS)

    Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi; Kawasaki, Shoichiro; Imamura, Shigehiro.

    1983-01-01

    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)

  5. [Mondini dysplasia: traumatic cerebrospinal fluid otorrhea with meningitis].

    Science.gov (United States)

    Kaftan, H; Adamaszek, M; Hosemann, W

    2006-08-01

    Mondini dysplasia is a rare malformation of the inner ear commonly associated with loss of hearing and vestibular function. Children with Mondini dysplasia are predisposed to developing a spontaneous cerebrospinal fluid (CSF) leak and recurrent meningitis. If there is no CSF leak but a unilateral hearing loss, the condition may go undiagnosed for years. We describe a 65-year-old man with unrecognized unilateral Mondini dysplasia who presented with CSF leak and meningoencephalitis after minor head trauma. Two operative interventions were undertaken to close the defect properly. Patients with Mondini dysplasia or their parents should be cautioned about the potential hazards of any head trauma.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    AIM: Assays for cerebrospinal fluid (CSF) levels of total tau, phospho-tau protein and beta-amyloid 1-42 have been available for some years. The aim of the study was to assess the usability of these biomarkers in a mixed population of tertiary dementia referral patients in a university-based memory......, the sensitivity of a single abnormal value was between 33 and 66%. The specificity was high except when discriminating AD from amnestic mild cognitive impairment. Two or more abnormal markers further increased the specificity and decreased the sensitivity. CONCLUSION: In a tertiary setting, abnormal CSF biomarker...

  7. Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease.

    Science.gov (United States)

    Chalbot, Sonia; Zetterberg, Henrik; Blennow, Kaj; Fladby, Tormod; Andreasen, Niels; Grundke-Iqbal, Inge; Iqbal, Khalid

    2011-01-01

    The role of blood-cerebrospinal fluid barrier (BCB) dysfunction in Alzheimer's disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinal fluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-β1-42 (Aβ1-42), and ubiquitin CSF levels. We found that due to its higher sensitivity, CSF sPLA2 activity could 1) discriminate AD from healthy controls and 2) showed BCB impairment in neurological control cases while QAlb could not. Moreover, the CSF sPLA2 activity measurement showed that around half of the AD patients were characterized by a BCB impairment. The BCB dysfunction observed in AD was independent from Mini-Mental State Examination score as well as CSF levels of total tau, Aβ1-42, and ubiquitin. Finally, the BCB dysfunction was not limited to any of the CSF biomarkers-based previously identified subgroups of AD. These results suggest that the BCB damage occurs independent of and probably precedes both Aβ and tau pathologies in a restricted subgroup of AD patients.

  8. Spectrophotometry of cerebrospinal fluid in subacute and chronic subdural haematomas

    Science.gov (United States)

    Kjellin, K. G.; Steiner, L.

    1974-01-01

    Spectrophotometric examinations were performed on cerebrospinal and subdural fluids in subacute (five patients) and chronic (20 patients) subdural haematomas, with special reference to the diagnostic aid of CSF spectrophotometry. Spectrophotometric xanthochromia of haemorrhagic origin was found in all CSFs examined, while definite visible xanthochromia was observed in only 28% and the CSF was judged as colourless in 52% of those cases. Characteristic bleeding patterns were found spectrophotometrically in all the 20 CSFs examined within 24 hours after lumbar puncture, haematoma patterns being detected in 90-95% of the cases. In many cases the electrophoretically separated protein fractions of CSF and subdural fluids were spectrophotometrically examined. In conclusion, CSF spectrophotometry is a simple, fast, and extremely sensitive method, which in our opinion should be used routinely in the diagnosis of suspected subdural haematomas, if lumbar puncture is not contraindicated. PMID:4140892

  9. Direct observation of cerebrospinal fluid bulk flow in the brain

    Science.gov (United States)

    Mestre, Humberto; Tithof, Jeffrey; Thomas, John; Kelley, Douglas; Nedergaard, Maiken

    2017-11-01

    Cerebrospinal fluid (CSF) serves a vital role in normal brain function. Its adequate flow and exchange with interstitial fluid through perivascular spaces (PVS) has been shown to be important in the clearance of toxic metabolites like amyloid- β, and its disturbance can cause severe neurological diseases. It has long been suspected that bulk flow may transport CSF, but limitations in imaging techniques have prevented direct observation of such flows in the PVS. In this talk, we describe a novel approach using high speed two photon laser scanning microscopy which has allowed for the first ever direct observation of CSF flow in the PVS of a mouse brain. By performing particle tracking velocimetry, we quantify the CSF bulk flow speeds and PVS geometry. This technique enables future studies of CSF flow disturbances on a new scale and will pave the way for evaluating the role of these fluxes in neurodegenerative disease. R01NS100366 (to M.N.).

  10. Hemosiderin-laden macrophages in the cerebrospinal fluid of a neonate after traumatic lumbar puncture.

    Science.gov (United States)

    Wusthoff, Courtney J; Abend, Nicholas S; Tennekoon, Gihan

    2008-01-01

    Macrophages in cerebrospinal fluid are described as indicators of pathology. We present findings from the lumbar puncture of a child without neurologic disease. Cerebrospinal fluid obtained after an initial, traumatic lumbar puncture attempt included a high proportion of macrophages, some containing erythrocyte fragments and hemosiderin. This suggests that although macrophages may indicate pathology, they can also accumulate after traumatic lumbar puncture.

  11. Osmolality of Cerebrospinal Fluid from Patients with Idiopathic Intracranial Hypertension (IIH)

    DEFF Research Database (Denmark)

    Wibroe, Elisabeth A; Yri, Hanne M; Jensen, Rigmor H

    2016-01-01

    INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial fluid pressure (ICP) of unknown etiology. This study aims to investigate osmolality of cerebrospinal fluid (CSF) from patients with IIH. METHODS: We prospectively collected CSF from individuals referred...

  12. Cerebrospinal fluid oto- and rhinorrhoea, diagnosis and treatment; Lekkasje av cerebrospinalvaeske, diagnostikk og behandling

    Energy Technology Data Exchange (ETDEWEB)

    Elverland, H.H. [Oestfold Central Hospital, Fredrikstand (Norway); Henning, R.; Lettrem, I.; Anke, I.M. [Tromsoe Regional Hospital, Tromsoe (Norway); Ulvestad, E. [Haukeland Sykehus, Bergen (Norway)

    1996-10-01

    Leakage of cerebrospinal fluid may occur after fracture of the skull base or after surgery on the skull base, nose, or paranasal sinuses. Further causes of cerebrospinal fluid leakage are tumours and malformations. It may also occur spontaneously. The authors describe four case reports illustrating diagnostic and surgical problems. Cerebrospinal fluid oto- and rhinorrhoea should be suspected in cases of recurring purulent meningitis. Immunologic demonstration of {beta}{sub 2}-transferrin in secretions from the nose and ear is a diagnostic sign of cerebrospinal fluid or perilymph. Digital subtraction cisternography, CT cisternography, and flowsensitive magnetic resonance imaging are sensitive methods for localizing dural leakage. Frontal craniotomy has been the traditional surgical approach. The recent evolvement of transnasal endoscopic sinus surgery and microsurgery has made it possible to treat cerebrospinal fluid oto- and rhinorrhoea with a high degree of success and less operative morbidity. 22 refs., 3 figs.

  13. Massive Cerebrospinal Fluid Leak of the Temporal Bone

    Directory of Open Access Journals (Sweden)

    Giannicola Iannella

    2016-01-01

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

  14. Memory Correlates of Alzheimer's Disease Cerebrospinal Fluid Markers

    DEFF Research Database (Denmark)

    Reijs, Babette L R; Ramakers, Inez H G B; Köhler, Sebastian

    2017-01-01

    -type dementia, and non-AD dementia from the European EDAR study. Assessment included CSF Aβ42 and t-tau analyses with INNO-BIA AlzBio3 Luminex assay, the CERAD wordlist learning and delayed recall, animal fluency test, and the CANTAB Paired Associates Learning (PAL) and Spatial Working Memory tasks. Follow...... on the wordlist learning, whereas increased CSF t-tau were associated with decline in scores on the wordlist learning, wordlist delayed recall, and animal fluency. Associations were independent of baseline diagnosis. CONCLUSION: Tests assessing episodic verbal and visuospatial memory are most useful for detection......BACKGROUND: Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease...

  15. Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.

    Science.gov (United States)

    Chiasserini, Davide; van Weering, Jan R T; Piersma, Sander R; Pham, Thang V; Malekzadeh, Arjan; Teunissen, Charlotte E; de Wit, Heidi; Jiménez, Connie R

    2014-06-25

    Extracellular vesicles (EVs) are present in human cerebrospinal fluid (CSF), yet little is known about their protein composition. The aim of this study is to provide a comprehensive analysis of the proteome of CSF EVs by electron microscopy and high resolution tandem mass spectrometry (MS/MS) in conjunction with bioinformatics. We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. Out of 1315 proteins, 760 were identified in both CSF pools and about 30% of those were also quantitatively enriched in the EV fraction versus the soluble CSF fraction. The proteome of CSF EVs was enriched in exosomal markers such as alix and syntenin-1, heat shock proteins and tetraspanins and contained a high proportion of brain-derived proteins (n=373). Interestingly, several known biomarkers for neurodegenerative diseases such as the amyloid precursor protein, the prion protein and DJ-1 were identified in the EV fractions. Our dataset represents the first comprehensive inventory of the EV proteome in CSF, underscoring the biomarker potential of this organelle. Further comparative studies on CSF EVs isolated from patients diagnosed with neurological disorders are warranted. Data are available via ProteomeXchange with identifier PXD000608. Biological significance In this study we analyzed the protein composition of extracellular vesicles isolated from pooled samples of human cerebrospinal fluid (CSF). CSF is a colorless fluid surrounding the brain and the spinal cord, important for the physiology of the central nervous system, ensuing mechanical protection, regulation of brain blood flow and elimination of byproducts of the brain. Since brain (patho)physiology is reflected in CSF, this biological fluid represents an ideal source of soluble and vesicle-based biomarkers for neurological diseases. Here we confirm the presence of exosome-like extracellular vesicles in CSF, underscoring

  16. Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

    Science.gov (United States)

    Vinther-Jensen, T; Simonsen, A H; Budtz-Jørgensen, E; Hjermind, L E; Nielsen, J E

    2015-10-01

    Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers. Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset. © 2015 EAN.

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

    International Nuclear Information System (INIS)

    Howden, L.; Aroussi, A.; Vloeberghs, M.

    2003-01-01

    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)

  18. Assay of cerebrospinal fluid protein: a rate biuret method evaluated.

    Science.gov (United States)

    Finley, P R; Williams, R J

    1983-01-01

    We evaluated a rate colorimetric method (Beckman) for measuring total protein in cerebrospinal fluid. The automated instrument we used was Beckman's ASTRA TM. A 100-microL sample of spinal fluid is introduced into the biuret reagent in the reaction cell and the increase in absorbance at 545 nm is monitored for 20.5 s. Solid-state circuits determine the rate of alkaline biuret-protein chelate formation, which is directly proportional to the total protein concentration in the sample. The linear range of measurement is 120 to 7500 mg/L. Day-to-day precision (CV) over the range of 150 to 1200 mg/L ranged from 15.2 to 2.3%. The method was unaffected by radical alteration of the albumin/globulin ratio, but there is a positive interference in the presence of hemoglobin, a suppression in the presence of bilirubin, and no effect by xanthochromia. The method is precise, accurate, rapid, and convenient. The method was compared with the trichloroacetic acid method as performed on the Du Pont aca III, giving a correlation coefficient (r2) of 0.9693. The method is precise, accurate, rapid, and convenient.

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

    Energy Technology Data Exchange (ETDEWEB)

    Howden, L.; Aroussi, A. [Univ. of Nottingham, School of Mechanical, Material, Manufacturing Engineering and Managements, Nottingham (United Kingdom)]. E-mail: eaxljh@nottingham.ac.uk; Vloeberghs, M. [Queens Medical Centre, Dept. of Child Health, Nottingham (United Kingdom)

    2003-07-01

    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)

  20. Using the cerebrospinal fluid to understand ingestive behavior.

    Science.gov (United States)

    Woods, Stephen C; May, Aaron A; Liu, Min; Tso, Patrick; Begg, Denovan P

    2017-09-01

    The cerebrospinal fluid (CSF) offers a window into the workings of the brain and blood-brain barrier (BBB). Molecules that enter into the central nervous system (CNS) by passive diffusion or receptor-mediated transport through the choroid plexus often appear in the CSF prior to acting within the brain. Other molecules enter the CNS by passing through the BBB into the brain's interstitial fluid prior to appearing in the CSF. This pattern is also often observed for molecules synthesized by neurons or glia within the CNS. The CSF is therefore an important conduit for the entry and clearance of molecules into/from the CNS and thereby constitutes an important window onto brain activity and barrier function. Assessing the CSF basally, under experimental conditions, or in the context of challenges or metabolic diseases can provide powerful insights about brain function. Here, we review important findings made by our labs, as influenced by the late Randall Sakai, by interrogating the CSF. Copyright © 2016. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2009-11-01

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

  2. Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves.

    Science.gov (United States)

    de Craene, B A; Deprez, P; D'Haese, E; Nelis, H J; Van den Bossche, W; De Leenheer, P

    1997-01-01

    Florfenicol, a fluorinated analog of thiamphenicol, is of great value in veterinary infectious diseases that formerly responded favorably to chloramphenicol. In view of the treatment of meningitis in calves, we studied its pharmacokinetics in the cerebrospinal fluid (CSF) and plasma of six animals. To this end, a new high-performance liquid chromatography method was developed which, unlike previous ones, uses solid-phase instead of double-phase extraction to isolate the drug. After a single intravenous dose of 20 mg/kg of body weight, a maximum concentration in CSF of 4.67 +/- 1.51 microg/ml (n = 6) was reached, with a mean residence time of 8.7 h. The decline of florfenicol in both CSF and plasma fitted a biexponential model with elimination half-lives of 13.4 and 3.2 h, respectively. Florfenicol penetrated well into CSF, as evidenced from an availability of 46% +/- 3% relative to plasma. The levels remained above the MIC for Haemophilus somnus over a 20-h period. Our results provide evidence indicating the effectiveness of florfenicol in the treatment of bacterial meningitis of calves. PMID:9303399

  3. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-05

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

  4. Virtual MRI endoscopy of the intracranial cerebrospinal fluid spaces

    International Nuclear Information System (INIS)

    Shigematsu, Y.; Korogi, Y.; Hirai, T.; Okuda, T.; Ikushima, I.; Sugahara, T.; Liang, L.; Ge, Y.; Takahashi, M.

    1998-01-01

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

  5. Utility of cerebrospinal fluid cortisol level in acute bacterial meningitis

    Science.gov (United States)

    Mehta, Anish; Mahale, Rohan R.; Sudhir, Uchil; Javali, Mahendra; Srinivasa, Rangasetty

    2015-01-01

    Background: Meningitis remains a serious clinical problem in developing as well as developed countries. Delay in diagnosis and treatment results in significant morbidity and mortality. The role and levels of intrathecal endogenous cortisol is not known. Objective: To study the cerebrospinal fluid (CSF) cortisol levels and to evaluate its role as a diagnostic and therapeutic marker in acute bacterial meningitis. Materials and Methods: Thirty patients with acute bacterial meningitis with no prior treatment were evaluated. Cortisol levels were compared with 20 patients with aseptic (viral) meningitis and 25 control subjects. Results: Mean CSF cortisol level was 13.85, 3.47, and 1.05 in bacterial meningitis, aseptic meningitis, and controls, respectively. Mean CSF cortisol level in bacterial meningitis was significantly higher as compared to controls (P meningitis (P meningitis. This suggests that intrathecalcortisol may serve as a valuable, rapid, relatively inexpensive diagnostic marker in discriminatingbetween bacterial and aseptic meningitis. This helps in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. PMID:26019421

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

    Science.gov (United States)

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

    2015-10-01

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Ville Leinonen

    2011-01-01

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

  8. Leptomeningeal carcinomatosis: prognostic implications of clinical and cerebrospinal fluid features.

    Science.gov (United States)

    Bruna, Jordi; González, Laura; Miró, Júlia; Velasco, Roser; Gil, Miguel; Tortosa, Avelina

    2009-01-15

    Leptomeningeal carcinomatosis (LC) represents a devastating complication of systemic cancer, and patients with LC have a dismal prognosis and increased mortality. The few studies that have focused on the evaluation of prognostic factors in patients with LC have resulted in contradictory results. Thus, the treatment of LC remains controversial, and no straightforward guidelines exist in the literature. The objective of the current study was to identify prognostic markers related to LC survival to better select patients who are eligible for intensive treatment. Seventy patients who had a diagnosis of LC were reviewed, and clinical data, cerebrospinal fluid (CSF) parameters, tumor-related characteristics, and treatment information were registered. The impact of single parameters on overall survival was determined by both univariate and multivariate analyses. The multivariate analysis revealed that Radiation Therapy Oncology Group scoreor=2.7 mmol/L (P=.001), the presence of infratentorial symptoms at onset (P=.026), and intrathecal treatment (P<.001) were associated independently with longer overall survival in patients with LC. In addition, the same clinical factors also predicted response to treatment in such patients. The predictive factors for patients with LC that were identified in this study could help to better select patients who are more likely to benefit from chemotherapy. Copyright (c) 2009 American Cancer Society.

  9. Florbetapir positron emission tomography and cerebrospinal fluid biomarkers

    Science.gov (United States)

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

    2015-01-01

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

  10. Dynamic oxygen-enhanced MRI of cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Taha M Mehemed

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

  11. A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin.

    Science.gov (United States)

    Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Holmans, Peter; Bertelsen, Sarah; Holtzman, David; Morris, John C; Bales, Kelly; Pickering, Eve H; Kauwe, John; Goate, Alison; Cruchaga, Carlos

    2016-01-01

    Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-08-28

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

  13. Establishing the proteome of normal human cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Steven E Schutzer

    2010-06-01

    Full Text Available Knowledge of the entire protein content, the proteome, of normal human cerebrospinal fluid (CSF would enable insights into neurologic and psychiatric disorders. Until now technologic hurdles and access to true normal samples hindered attaining this goal.We applied immunoaffinity separation and high sensitivity and resolution liquid chromatography-mass spectrometry to examine CSF from healthy normal individuals. 2630 proteins in CSF from normal subjects were identified, of which 56% were CSF-specific, not found in the much larger set of 3654 proteins we have identified in plasma. We also examined CSF from groups of subjects previously examined by others as surrogates for normals where neurologic symptoms warranted a lumbar puncture but where clinical laboratory were reported as normal. We found statistically significant differences between their CSF proteins and our non-neurological normals. We also examined CSF from 10 volunteer subjects who had lumbar punctures at least 4 weeks apart and found that there was little variability in CSF proteins in an individual as compared to subject to subject.Our results represent the most comprehensive characterization of true normal CSF to date. This normal CSF proteome establishes a comparative standard and basis for investigations into a variety of diseases with neurological and psychiatric features.

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

    Directory of Open Access Journals (Sweden)

    Monique Albersen

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

  15. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Aylin Yilmaz

    2009-09-01

    Full Text Available Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF and plasma in subjects receiving antiretroviral treatment regimens containing this drug.Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma.Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0. The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180. CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations.Approximately 50% of the CSF specimens exceeded the IC(95 levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Luykx, Jurjen J; Bakker, Steven C; Lentjes, Eef; Boks, Marco P M; van Geloven, Nan; Eijkemans, Marinus J C; Janson, Esther; Strengman, Eric; de Lepper, Anne M; Westenberg, Herman; Klopper, Kai E; Hoorn, Hendrik J; Gelissen, Harry P M M; Jordan, Julian; Tolenaar, Noortje M; van Dongen, Eric P A; Michel, Bregt; Abramovic, Lucija; Horvath, Steve; Kappen, Teus; Bruins, Peter; Keijzers, Peter; Borgdorff, Paul; Ophoff, Roel A; Kahn, René S

    2012-01-01

    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. 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. 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.

  18. Comparative analysis of monoaminergic cerebrospinal fluid-contacting cells in Osteichthyes (bony vertebrates).

    Science.gov (United States)

    Xavier, Anna L; Fontaine, Romain; Bloch, Solal; Affaticati, Pierre; Jenett, Arnim; Demarque, Michaël; Vernier, Philippe; Yamamoto, Kei

    2017-06-15

    Cerebrospinal fluid-contacting (CSF-c) cells containing monoamines such as dopamine (DA) and serotonin (5-HT) occur in the periventricular zones of the hypothalamic region of most vertebrates except for placental mammals. Here we compare the organization of the CSF-c cells in chicken, Xenopus, and zebrafish, by analyzing the expression of synthetic enzymes of DA and 5-HT, respectively, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), and draw an evolutionary scenario for this cell population. Due to the lack of TH immunoreactivity in this region, the hypothalamic CSF-c cells have been thought to take up DA from the ventricle instead of synthesizing it. We demonstrate that a second TH gene (TH2) is expressed in the CSF-c cells of all the three species, suggesting that these cells do indeed synthetize DA. Furthermore, we found that many CSF-c cells coexpress TH2 and TPH1 and contain both DA and 5-HT, a dual neurotransmitter phenotype hitherto undescribed in the brain of any vertebrate. The similarities of CSF-c cells in chicken, Xenopus, and zebrafish suggest that these characteristics are inherited from the common ancestor of the Osteichthyes. A significant difference between tetrapods and teleosts is that teleosts possess an additional CSF-c cell population around the posterior recess (PR) that has emerged in specific groups of Actinopterygii. Our comparative analysis reveals that the hypothalamus in mammals and teleosts has evolved in a divergent manner: placental mammals have lost the monoaminergic CSF-c cells, while teleosts have increased their relative number. © 2017 Wiley Periodicals, Inc.

  19. Serial cerebrospinal fluid neurofilament heavy chain levels in severe Guillain-Barre syndrome

    NARCIS (Netherlands)

    Dujmovic, I.; Lunn, M.P.; Reilly, M.M.; Petzold, A.

    2013-01-01

    Introduction: Proximal axonotmesis results in the release of neurofilament (Nf) proteins into the cerebrospinal fluid (CSF) in patients with Guillain-Barré syndrome (GBS). High CSF levels of the phosphorylated form of Nf-heavy chain (NfH

  20. Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid

    NARCIS (Netherlands)

    Mason, Shayne; Reinecke, Carolus J.; Kulik, Willem; van Cruchten, Arno; Solomons, Regan; van Furth, A. Marceline Tutu

    2016-01-01

    The defining feature of the cerebrospinal fluid (CSF) collected from infants and children with tuberculous meningitis (TBM), derived from an earlier untargeted nuclear magnetic resonance (NMR) metabolomics study, was highly elevated lactic acid. Undetermined was the contribution from host response

  1. Selective localization of IgG from cerebrospinal fluid to brain parenchyma

    DEFF Research Database (Denmark)

    Mørch, Marlene Thorsen; Forsberg Sørensen, Sofie; Khorooshi, Reza M. H.

    2018-01-01

    . The paradigmatic autoantibodies in NMOSD are specific for the water channel aquaporin-4, localized to astrocytic end-feet at the blood-brain barrier and ependymal cells at the cerebrospinal fluid-brain barrier. We have previously observed that IgG antibodies from NMO patients (NMO-IgG) access brain parenchyma from...... the cerebrospinal fluid and induce subpial and periventricular NMO-like lesions and blood-brain barrier breakdown, in a complement-dependent manner. To investigate how IgG trafficking from cerebrospinal fluid to brain parenchyma can be influenced by injury. IgG from healthy donors was intrathecally injected...... into the cerebrospinal fluid via cisterna magna at 1, 2, 4, or 7 days after a distal stereotactic sterile needle insertion to the striatum. Antibody deposition, detected by staining for human IgG, peaked 1 day after the intrathecal injection and was selectively seen close to the needle insertion. When NMO...

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

    NARCIS (Netherlands)

    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.

  3. Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis

    NARCIS (Netherlands)

    Weisfelt, Martijn; Determann, Rogier M.; de Gans, Jan; van der Ende, Arie; Levi, Marcel; van de Beek, Diederik; Schultz, Marcus J.

    2007-01-01

    OBJECTIVES: This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. METHODS: CSF was collected from 92 adults with community-acquired bacterial meningitis, who

  4. Contrast enhancement of the cerebrospinal fluid on MRI in two cases of spirochaetal meningitis

    International Nuclear Information System (INIS)

    Good, C.D.; Jaeger, H.R.

    2000-01-01

    We report two patients with meningitis due to spirochaetal infection, both of whom showed diffusely enhancing meninges around the brain and spinal cord. In addition, there was enhancement of the cerebrospinal fluid after intravenous administration of Gd-DTPA. (orig.)

  5. Oligoclonal Immunoglobulins in Cerebrospinal Fluid during Varicella Zoster Virus (VZV) Vasculopathy Are Directed against VZV

    OpenAIRE

    Burgoon, Mark P.; Hammack, Barbara N.; Owens, Gregory P.; Maybach, Amy L.; Judith Eikelenboom, M.; Gilden, Donald H.

    2003-01-01

    Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebro-spinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise ...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. Neuromyelitis optica IgG in the cerebrospinal fluid induces astrocytopathy in optic nerve

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Lillevang, Søren Thue; Mørch, Marlene

    -ON. The predilection of the optic nerve in NMOSD may partly be explained by the dense expression of AQP4 in the optic nerve. We previously reported that AQP4-IgG in cerebrospinal fluid (CSF) becomes widely distributed in the brain and causes complementdependent astrocyte injury in periventricular areas and brain...... of brain-specific antibodies in cerebrospinal fluid. Journal of neuroimmunology 2013;254:76-82....

  8. What does an isolated cerebrospinal fluid band mean: a tertiary centre experience

    Directory of Open Access Journals (Sweden)

    Turan Poyraz

    2015-04-01

    Full Text Available Introduction: The presence of oligoclonal bands in cerebrospinal fluid of multiple sclerosis patients is now well established to support the clinical diagnosis. On the other hand, a single band response can represent the initial stage of an oligoclonal response, before the other antibody clones become visible. Method: The aim of the current study was to evaluate the presence of an isolated cerebrospinal fluid single immunoglobulin band, and to analyse the clinical and radiological diagnosis of the samples with a single immunoglobulin band. In this study, 3524 cerebrospinal fluid samples were re-examined using agarose gel isoelectric focusing, and ones with an isolated cerebrospinal fluid immunoglobulin band were detected. Results: A single band in cerebrospinal fluid was detected in 1.4% samples. A clinically isolated syndrome was diagnosed in 27.5%of them, relapsing remitting multiple sclerosis in 49%, secondary progressive multiple sclerosis in 11.8%, and radiologically isolated syndrome in 2%. No primary progressive multiple sclerosis patient was found. All Barkhoff criteria were met in 90.1% of them. The remaining were diagnosed with other inflammatory neurological diseases (9.8%. Conclusion: The presence of an isolated cerebrospinal fluid monoclonal immunoglobulin band is rare. Although most of the samples were diagnosed as multiple sclerosis according to both clinical and paraclinical (magnetic resonance imaging parameters, they had only a single immunoglobulin band in cerebrospinal fluid. Not only oligoclonal bands, but also an isolated cerebrospinal fluid single band might be a cornerstone for the diagnosis of multiple sclerosis at least for some patients.

  9. Cytomegalovirus Antibody in Cerebrospinal Fluid of Schizophrenic Patients Detected by Enzyme Immunoassay

    Science.gov (United States)

    Fuller Torrey, E.; Yolken, Robert H.; Winfrey, C. Jack

    1982-05-01

    By means of enzyme immunoassay techniques to detect the presence of antibody to cytomegalovirus, the cerebrospinal fluid of 178 patients with schizophrenia, 17 patients with bipolar disorders, and 11 other psychiatric patients was compared with that of 79 neurological patients and 41 normal control subjects. The cerebrospinal fluid of 20 of the schizophrenic patients and 3 of the patients with bipolar disorders showed significant increases in immunoglobulin M antibody to cytomegalovirus; no difference was found in patients on or off psychotropic medications.

  10. Metabolite profile of cerebrospinal fluid in patients with spina bifida: a proton magnetic resonance spectroscopy study.

    Science.gov (United States)

    Pal, Kamalesh; Sharma, Uma; Gupta, D K; Pratap, Akshay; Jagannathan, N R

    2005-02-01

    The present study was carried out to assess the metabolic differences between cerebrospinal fluid samples of patients with spina bifida and age-matched control individuals. To study the metabolite profile of cerebrospinal fluid of patients with spina bifida using proton magnetic resonance spectroscopy, compare the levels of metabolites with controls, establish correlation of underlying neuronal dysfunction with metabolic changes in patients with spina bifida, and evaluate the potential use of this technique as an additional tool for diagnostic assessment. Combination of embryopathy, stretching, ischemia, compression, and trauma is responsible for cord dysfunction in spina bifida. Changes in neuronal metabolism leads to changes in the local milieu of cerebrospinal fluid in the cord. Change in metabolite profile of cerebrospinal fluid in spina bifida in terms of increase in products of anaerobic metabolism, nerve membrane integrity, and nerve ischemia has not yet been studied. Cerebrospinal fluid obtained from patients and control individuals were characterized using various one- and two-dimensional proton magnetic resonance spectroscopy techniques. Concentration of various metabolites was calculated using the area under the nuclear magnetic resonance peak. Statistically significantly higher levels of lactate, choline, glycerophosphocholine, acetate, and alanine in the cerebrospinal fluid of patients with spina bifida was observed compared with control individuals. Significantly higher levels of metabolites were observed in patients with spina bifida, representing a state of nerve ischemia, anaerobic metabolism, and disruption of neuronal membrane.

  11. Insights into cerebrospinal fluid and cerebral blood flows in infants and young children.

    Science.gov (United States)

    Capel, Cyrille; Makki, Malek; Gondry-Jouet, Catherine; Bouzerar, Roger; Courtois, Véronique; Krejpowicz, Bénédicte; Balédent, Olivier

    2014-12-01

    This study investigates the craniospinal flows of blood and cerebrospinal fluid using phase-contrast magnetic resonance imaging (MRI) on 23 control neonates and infants (5 d-68 mo old). Mean arterial cerebral blood flow increased with age of infant from 180 mL/min after birth to 1330 mL/min around 6 years of age. This corresponds to 51 mL/min/100 g and 95 mL/min/100 g, respectively. Cervical cerebrospinal fluid stroke volume increased from 38 × 10(-3) mL to 752 × 10(-3) mL per cardiac cycle. After arterial systolic blood inflow, we observed a delay of the venous outflow that was always preceded by cerebrospinal fluid flushing out through the spinal canal. These results highlighted the importance of compliance of the spinal compartment and the interaction of blood and cerebrospinal fluid dynamics. The capacity of the spinal compartment to receive intracranial cerebrospinal fluid in presence of fontanels was demonstrated. We provide reference values to understand the physiology of cerebrospinal fluid and cerebral blood. © The Author(s) 2013.

  12. The cerebrospinal fluid in multiple sclerosis: far beyond the bands.

    Science.gov (United States)

    Domingues, Renan Barros; Fernandes, Gustavo Bruniera Peres; Leite, Fernando Brunale Vilela de Moura; Tilbery, Charles Peter; Thomaz, Rodrigo Barbosa; Silva, Gisele Sampaio; Mangueira, Cristóvão Luis Pitangueira; Soares, Carlos Augusto Senne

    2017-01-01

    The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions. RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos

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

    Directory of Open Access Journals (Sweden)

    Alexandre Wullschleger

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

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Cerebrospinal fluid concentrations of antituberculosis agents in adults and children.

    Science.gov (United States)

    Donald, P R

    2010-09-01

    Tuberculous meningitis (TBM) causes a devastating morbidity and mortality in adults and children. Even in patients presenting at an early stage of disease, deterioration may occur despite apparently adequate therapy. The literature relating to cerebrospinal fluid penetration of antituberculosis agents is reviewed. Amongst the essential antituberculosis agents isoniazid has the best CSF pharmacokinetics reaching peak concentrations (C(max)) only slightly less than in blood. Pyrazinamide also has good CSF penetration and in children receiving dosages of 40 mg/kg the CSF C(max) exceeds the proposed minimal inhibitory concentration of 20 μg/ml. Streptomycin other aminoglycosides and ethambutol have poor CSF penetration and cannot be agents of first choice for TBM treatment. Rifampicin at dosages used in adults seldom reaches CSF concentrations exceeding MIC, but does so more frequently in children when dosages of up to 20 mg/kg are used. The non-essential agents ethionamide, the fluoroquinolones, with the exception of ciprofloxacin, and cycloserine (terizadone) have relatively good CSF penetration and are recommended for TBM treatment. The dosages of the essential agents recommended for the treatment of TBM in children are INH 10 mg/kg (range 6-15 mg/kg bodyweight), rifampicin 15 mg/kg (range 10-20 mg/kg), pyrazinamide 35 mg/kg (range 30-40 mg/kg), ethambutol 20 mg/kg (range 15-25 mg/kg) and streptomycin 15 mg/kg (range 12-18 mg/kg). Amongst second-line agents ofloxacin, levofloxacin and moxifloxacin should be used in dosages of 15-20 mg/kg, ethionamide 20 mg/kg in a single dose, if tolerated, and for cycloserine (terizadone) 15 mg/kg. Antituberculous chemotherapy should be started as soon as the diagnosis of TBM is considered. Copyright © 2010. Published by Elsevier Ltd.

  16. Elevated cerebrospinal fluid tau protein levels in Wernicke's encephalopathy.

    Science.gov (United States)

    Matsushita, Sachio; Miyakawa, Tomohiro; Maesato, Hitoshi; Matsui, Toshifumi; Yokoyama, Akira; Arai, Hiroyuki; Higuchi, Susumu; Kashima, Haruo

    2008-06-01

    Limited neuronal cell loss is seen in the neuropathology of Wernicke's encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer's disease (AD) as a disease control. CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme-linked immunosorbent assay. Tau phosphorylated at threonine 181 (p-tau(181)) and amyloid beta-protein ending at amino acid 42 (A beta 42) in CSF were also determined for comparison between acute WE with AD. Total tau was significantly elevated in acute WE and decreased on long-term follow-up, but was not elevated in WD or KS. The patterns of p-tau(181) and A beta 42 differed between acute WE and AD. Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.

  17. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

    Directory of Open Access Journals (Sweden)

    Rosengren Lars

    2009-12-01

    Full Text Available Abstract Background Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF biomarkers related of amyloid and tau metabolism in HIV-infected patients. Methods In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ, amyloid beta fragment 1-42 (Aβ1-42, and total and hyperphosphorylated tau (t-tau and p-tau in CSF of 86 HIV-infected (HIV+ subjects, including 21 with AIDS dementia complex (ADC, 25 with central nervous system (CNS opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV- subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. Results CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Conclusions Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those

  18. Critical postcraniotomy cerebrospinal fluid hypovolemia: risk factors and outcome analysis.

    Science.gov (United States)

    Komotar, Ricardo J; Ransom, Evan R; Mocco, J; Zacharia, Brad E; McKhann, Guy M; Mayer, Stephan A; Connolly, E Sander

    2006-08-01

    Critical cerebrospinal fluid (CSF) hypovolemia may cause acute postoperative clinical deterioration in aneurysmal subarachnoid hemorrhage patients after craniotomy for microsurgical aneurysm clipping. We sought to identify risk factors for critical CSF hypovolemia and determine this syndrome's effect on clinical outcome. Between April 2001 and June 2004 at Columbia University Medical Center, 16 aneurysmal subarachnoid hemorrhage patients were diagnosed with postoperative critical CSF hypovolemia, whereas 151 patients who underwent craniotomy for clipping were not. The demographics, as well as the presenting radiographic and clinical characteristics, of these groups were evaluated. In addition, a 2:1 matched case-control comparison of patients with and without critical CSF hypovolemia was completed using clinical data, operative variables, and outcome data. Outcome analysis was performed with a battery of tests designed to assess global outcome, cognitive function, independence, and quality of life. There was no difference in clinical grade, Fisher score, age, and sex distribution between patients diagnosed with critical CSF hypovolemia and the general aneurysmal subarachnoid hemorrhage population at Columbia University Medical Center. Subsequent 2:1 matched case-control comparison demonstrated a higher incidence of global cerebral edema on admission computed tomographic scans (75 versus 31%; P < 0.01) and a significantly longer operative time for patients with critical CSF hypovolemia (5 h 18 min versus 4 h 22 min; P < 0.03). No significant differences were observed between groups in outcome assessments at the time of hospital discharge or the 3-month follow-up examination. Risk factors associated with an increased incidence of critical CSF hypovolemia after aneurysm surgery include the presence of global cerebral edema on admission head computed tomographic scans and prolonged operative time. In such patients, heightened suspicion of CSF hypovolemia is crucial

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

    Directory of Open Access Journals (Sweden)

    Fellmann Jere

    2006-05-01

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

  20. Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

    Science.gov (United States)

    de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

    2017-09-01

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  1. Cerebrospinal fluid biomarker candidates associated with human WNV neuroinvasive disease.

    Directory of Open Access Journals (Sweden)

    Christophe Fraisier

    Full Text Available During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF cases, but also of West Nile neuroinvasive disease (WNND. The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS structures, modifications in the cerebrospinal fluid (CSF composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1, a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12. The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution.

  2. Lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis

    Directory of Open Access Journals (Sweden)

    An-Ran Xu

    2016-06-01

    Full Text Available Objective: To study the lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis and their correlation with disease. Methods: Children with viral encephalitis were selected as VE group, children excluded of central nervous system infection by lumbar puncture or children without central nervous system diseases but receiving surgery with spinal anesthesia were selected as control group, and then cerebrospinal fluid and serum were collected to detect lymphocyte subset contents, nerve injury molecule contents as well as inflammatory response indicators and oxidative stress response indicators. Results: CD3+, CD3+CD4+, CD4/CD8 and CD16+CD56+ in cerebrospinal fluid of VE group were lower than those of control group, and both CD3+CD8+ and CD19+ were higher than those of control group; CD3+, CD3+CD4+, CD4/CD8 and CD16+CD56+ in cerebrospinal fluid of children with abnormal MRI were lower than those of children with normal MRI, and both CD3+CD8+ and CD19+ were higher than those of children with normal MRI; NSE, MBP, S-100 and NPT contents in cerebrospinal fluid and serum of VE group were significantly higher than those of control group and had good correlation with lymphocyte subset contents; MMP9, TNF-α and IL-6 contents in cerebrospinal fluid of VE group were significantly higher than those of control group, and SOD and GSH-Px contents were significantly lower than those of control group and had good correlation with lymphocyte subset contents. Conclusions: CD4+/CD8+T lymphocyte ratio and NK cell content decrease, and B lymphocyte content increases in cerebrospinal fluid of children with viral encephalitis, and lymphocyte subset contents have inhibitory effect on MRI manifestation, degree of inflammatory response and oxidative stress response.

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

    International Nuclear Information System (INIS)

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-01-01

    Cerebrospinal fluid flow dynamics were evaluated by 111 In-diethylenetriamine pentaacetic acid ( 111 In-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 111 In-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

  4. Biochemical Analysis of Synovial Fluid, Cerebrospinal Fluid and Vitreous Humor at Early Postmortem Intervals in Donkeys

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    Doha Yahia

    2014-01-01

    Full Text Available Biochemical analysis of body fluids after death is a helpful tool in veterinary forensic medicine. Synovial fluid, cerebrospinal fluid (CSF and vitreous humor are easily accessible and well preserved from contamination. Five donkeys (Equus africanus asinus aged 1 - 2 years old were subjected to the study. Samples (Synovial fluid, CSF and vitreous humor were collected before death (antimortem and then at 2, 4, 6, 8, 10 and 12 hours postmortem. Samples were analyzed for glucose, chloride, sodium, magnesium, potassium, enzymes and total protein. Synovial fluid analysis showed that glucose concentration started to decrease at 6 hours postmortem, while magnesium level increased with time. Other parameters were more stable. CSF analysis showed several changes related to time after death as the decrease in glucose and sodium levels, and the increased levels of potassium, magnesium, calcium and total protein. Vitreous analysis revealed a reduction in glucose level and increased potassium and magnesium concentrations. The present study concluded that biochemical analysis of synovial fluid, vitreous humor and CSF can help in determination of time since death in donkeys. This study recommend using CSF for determination of early post-mortem intervals.

  5. Cerebrospinal Fluid Treponema pallidum Particle Agglutination Assay for Neurosyphilis Diagnosis.

    Science.gov (United States)

    Marra, Christina M; Maxwell, Clare L; Dunaway, Shelia B; Sahi, Sharon K; Tantalo, Lauren C

    2017-06-01

    Limited data suggest that the cerebrospinal fluid Treponema pallidum particle agglutination assay (CSF-TPPA) is sensitive and a CSF Treponema pallidum hemagglutination assay (CSF-TPHA) titer of ≥1:640 is specific for neurosyphilis diagnosis. CSF-TPPA reactivity and titer were determined for a convenience sample of 191 CSF samples from individuals enrolled in a study of CSF abnormalities in syphilis (training data set). The sensitivity of a reactive test and the specificity for reactivity at serial higher CSF dilutions were determined. Subsequently, CSF-TPPA reactivity at a 1:640 dilution was determined for all available samples from study participants enrolled after the last training sample was collected (validation data set, n = 380). Neurosyphilis was defined as (i) a reactive CSF Venereal Disease Research Laboratory test (CSF-VDRL), (ii) detection of T. pallidum in CSF by reverse transcriptase PCR, or (iii) new vision loss or hearing loss. In the training data set, the diagnostic sensitivities of a reactive CSF fluorescent treponemal antibody absorption test (CSF-FTA-ABS) and a reactive CSF-TPPA did not differ significantly (67 to 98% versus 76 to 95%). The specificity of a CSF-TPPA titer of ≥1:640 was significantly higher than that of lower dilutions and was not significantly different from that of CSF-VDRL. In the validation data set, the diagnostic specificity of a CSF-TPPA titer of ≥1:640 was high and did not differ significantly from that of CSF-VDRL (93 to 94% versus 90 to 91%). Ten CSF samples with a nonreactive CSF-VDRL had a CSF-TPPA titer of ≥1:640. If a CSF-TPPA titer of ≥1:640 was used in addition to a reactive CSF-VDRL, the number of neurosyphilis diagnoses would have increased from 47 to 57 (21.3%). A CSF-TPPA titer cutoff of ≥1:640 may be useful in identifying patients with neurosyphilis when CSF-VDRL is nonreactive. Copyright © 2017 American Society for Microbiology.

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

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    Street Jonathan M

    2012-01-01

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

  7. Mannan-binding lectin in cerebrospinal fluid: a leptomeningeal protein

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    Reiber Hansotto

    2012-08-01

    Full Text Available Abstract Background Mannan-binding lectin (MBL, a protein of the innate immune response is attracting increasing clinical interest, in particularly in relation to its deficiency. Due to its involvement in brain diseases, identifying the source of MBL in CSF is important. Analysis of cerebrospinal fluid (CSF can provide data that discriminates between blood-, brain-, and leptomeninges-derived proteins. To detect the source of MBL in CSF we need to consider three variables: the molecular size-dependent concentration gradient between CSF and blood, the variation in transfer between blood and CSF, and the CSF MBL concentration correlation with the albumin CSF/serum quotient (QAlb, i.e., with CSF flow rate. Methods MBL was assayed in samples of CSF and serum with an ELISA, coated with anti MBL antibodies. Routine parameters such as albumin-, immunoglobulin- CSF/serum quotients, oligoclonal IgG and cell count were used to characterize the patient groups. Groups comprised firstly, control patients without organic brain disease with normal CSF and normal barrier function and secondly, patients without inflammatory diseases but with increased QAlb, i.e. with a blood CSF barrier dysfunction. Results MBL concentration in CSF was at least five-fold higher than expected for a molecular-size-dependent passage from blood. Secondly, in a QIgM/QAlb quotient diagram (Reibergram 9/13 cases showed an intrathecal fraction in some cases over 80% of total CSF MBL concentration 3 The smaller inter-individual variation of MBL concentrations in CSF of the control group (CV = 66% compared to the MBL concentrations in serum (CV = 146% indicate an independent source of MBL in CSF. 4 The absolute MBL concentration in CSF increases with increasing QAlb. Among brain-derived proteins in CSF only the leptomeningeal proteins showed a (linear increase with decreasing CSF flow rate, neuronal and glial proteins are invariant to changes of QAlb. Conclusions MBL in CSF is

  8. Clinical features and pharmacotherapy of childhood monoamine neurotransmitter disorders.

    Science.gov (United States)

    Ng, J; Heales, S J R; Kurian, M A

    2014-08-01

    Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. The diagnosis of neurotransmitter disorders is made through detailed clinical assessment, analysis of cerebrospinal fluid neurotransmitters, and further supportive diagnostic investigations. Early and accurate diagnosis of neurotransmitter disorders is important, as many are amenable to therapeutic intervention. The principles of treatment for monoamine neurotransmitter disorders are mainly directly derived from understanding these metabolic pathways. In disorders characterized by enzyme deficiency, we aim to increase monoamine substrate availability, boost enzyme co-factor levels, reduce monoamine breakdown, and replace depleted levels of monoamines with pharmacological analogs as clinically indicated. Most monoamine neurotransmitter disorders lead to reduced levels of central dopamine and/or serotonin. Complete amelioration of motor symptoms is achievable in some disorders, such as Segawa's syndrome, and, in other conditions, significant improvement in quality of life can be attained with pharmacotherapy. In this review, we provide an overview of the clinical features and current treatment strategies for childhood monoamine neurotransmitter disorders.

  9. Cerebrospinal Fluid Amyloid β40 Is Decreased in Cerebral Amyloid Angiopathy

    Science.gov (United States)

    Verbeek, Marcel M.; Kremer, Berry P. H.; Rikkert, Marcel Olde; van Domburg, Peter H. M. F.; Skehan, Maureen E.; Greenberg, Steven M.

    2013-01-01

    Cerebral amyloid angiopathy is caused by deposition of the amyloid β protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid β40 and β42 proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid β40 (p < 0.01 vs controls or Alzheimer disease) and amyloid β42 concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid β42 and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid β40 as well as amyloid β42 protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid β proteins toward the cerebrospinal fluid. PMID:19743453

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

    Directory of Open Access Journals (Sweden)

    V. B. Musatov

    2015-01-01

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

  11. Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR.

    Science.gov (United States)

    Luykx, J J; Bakker, S C; van Geloven, N; Eijkemans, M J C; Horvath, S; Lentjes, E; Boks, M P M; Strengman, E; DeYoung, J; Buizer-Voskamp, J E; Cantor, R M; Lu, A; van Dongen, E P A; Borgdorff, P; Bruins, P; Kahn, R S; Ophoff, R A

    2013-10-08

    Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.

  12. A consensus protocol for the standardisation of cerebrospinal fluid collection and biobanking

    NARCIS (Netherlands)

    Teunissen, C.E.; Petzold, A.F.S.; Bennett, J.L.; Berven, F.S.; Brundin, L.; Comabella, M.; Franciotta, D.; Federiksen, J.L.; Fleming, J.O.; Furlan, R.; Hintzen, R.Q.; Hughes, S.G.; Johnson, M.H.; Krasulova, E.; Kuhle, J.; Magnone, M.C.; Rajda, C.; Rejdak, K.; Schmidt, H.K.; van Pesch, V.; Waubant, E.; Wolf, C.; Giovannoni, G.; Deisenhammer, F.; Hegen, H.; Hemmer, B.; Tumani, H.T.

    2010-01-01

    There is a long history of research on body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only very few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering

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

    Czech Academy of Sciences Publication Activity Database

    Çökeliler, D.; Caner, H.; Zemek, Josef; Choukourov, A.; Biederman, H.; Mutlu, M.

    2007-01-01

    Roč. 2, č. 1 (2007), s. 39-47 ISSN 1748-6041 Grant - others:TUBITAK(TR) MISAG-COST 527 Institutional research plan: CEZ:AV0Z10100521 Keywords : shunt infections * cerebrospinal * PP HEMA * biomaterials Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.787, year: 2007

  14. Measurement of Interleukin-6 in Cerebrospinal Fluid for the Diagnosis of Bacterial Meningitis.

    Science.gov (United States)

    Dano, Ibrahim Dan; Sadou, Hassimi; Issaka, Bassira; Oukem-Boyer, Odile Ouwe Missi

    It is assessed whether the measurement of interleukin-6 in the cerebrospinal fluid can serve as a biomarker for the diagnosis of bacterial meningitis. Cerebrospinal fluid was obtained from 152 patients aged 0-15 years suspected of having meningitis. These patients were classified into the following groups: Bacterial meningitis (n = 85), aseptic meningitis (n = 35) and non-meningitis/control (n = 32) based on leukocyte count and bacterial identification by culture and molecular biology. Interleukin-6 concentrations in cerebrospinal fluid were measured by enzyme-linked immunosorbent assay. This study found a significant difference of the mean cerebrospinal fluid interleukin-6 level (p≤0.01) between patients with bacterial meningitis (3,538.69±2,560.78 pg mL -1) and patients with aseptic meningitis (332.51±470.69 pg mL -1) or those of the control group (205.83±79.39 pg mL -1). There was also a significant difference of the mean cerebrospinal fluid interleukin-6 level between patients with aseptic meningitis and those of the control group. Interleukin-6 had the highest area under the ROC curve: 0.94 (95% confidence interval: 0.901-0.979) compared to that of cerebrospinal fluid glucose and total protein. At a cut-off value of 1,065.96 pg mL -1, interleukin-6 had a sensitivity of 76.2% and specificity of 100%. Interleukin-6 is a potential biomarker for the differential diagnosis of meningitis.

  15. Oligoclonal immunoglobulins in cerebrospinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV.

    Science.gov (United States)

    Burgoon, Mark P; Hammack, Barbara N; Owens, Gregory P; Maybach, Amy L; Eikelenboom, M Judith; Gilden, Donald H

    2003-10-01

    Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebrospinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause.

  16. Cerebrospinal fluid biomarkers for Parkinson's disease and L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas

    the development of biomarkers for earlier and more precise diagnosis and prognosis. The purpose of this study is the development and evaluation of proposed biomarkers in the cerebrospinal fluid (CSF) of rat models of PD and LID as well as in patients with early and late stage PD with or without LID. Potential....... Cerebrospinal fluid biomarkers in Parkinson disease. Nature reviews Neurology. 2013;9(3):131-40. 5. Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Movement...

  17. Cerebrospinal fluid dynamics at the lumbosacral level in patients with spinal stenosis: A pilot study.

    Science.gov (United States)

    Chun, Se-Woong; Lee, Hack-Jin; Nam, Koong-Ho; Sohn, Chul-Ho; Kim, Kwang Dong; Jeong, Eun-Jin; Chung, Sun G; Kim, Keewon; Kim, Dong-Joo

    2017-01-01

    Spinal stenosis is a common degenerative condition. However, how neurogenic claudication develops has not been clearly elucidated. Moreover, cerebrospinal fluid physiology at the lumbosacral level has not received adequate attention. This study was conducted to compare cerebrospinal fluid hydrodynamics at the lumbosacral spinal level between patients with spinal stenosis and healthy controls. Twelve subjects (four patients and eight healthy controls; 25-77 years old; seven males) underwent phase-contrast magnetic resonance imaging to quantify cerebrospinal fluid dynamics. The cerebrospinal fluid flow velocities were measured at the L2 and S1 levels. All subjects were evaluated at rest and after walking (to provoke neurogenic claudication in the patients). The caudal peak flow velocity in the sacral spine (-0.25 ± 0.28 cm/s) was attenuated compared to that in the lumbar spine (-0.93 ± 0.46 cm/s) in both patients and controls. The lumbar caudal peak flow velocity was slower in patients (-0.65 ± 0.22 cm/s) than controls (-1.07 ± 0.49 cm/s) and this difference became more pronounced after walking (-0.66 ± 0.37 cm/s in patients, -1.35 ± 0.52 cm/s in controls; p = 0.028). The sacral cerebrospinal fluid flow after walking was barely detectable in patients (caudal peak flow velocity: -0.09 ± 0.03 cm/s). Cerebrospinal fluid dynamics in the lumbosacral spine were more attenuated in patients with spinal stenosis than healthy controls. After walking, the patients experiencing claudication did not exhibit an increase in the cerebrospinal fluid flow rate as the controls did. Altered cerebrospinal fluid dynamics may partially explain the pathophysiology of spinal stenosis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:104-112, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects

    Science.gov (United States)

    Toledo, Jon B.; Zetterberg, Henrik; van Harten, Argonde C.; Glodzik, Lidia; Martinez-Lage, Pablo; Bocchio-Chiavetto, Luisella; Rami, Lorena; Hansson, Oskar; Sperling, Reisa; Engelborghs, Sebastiaan; Osorio, Ricardo S.; Vanderstichele, Hugo; Vandijck, Manu; Hampel, Harald; Teipl, Stefan; Moghekar, Abhay; Albert, Marilyn; Hu, William T.; Monge Argilés, Jose A.; Gorostidi, Ana; Teunissen, Charlotte E.; De Deyn, Peter P.; Hyman, Bradley T.; Molinuevo, Jose L.; Frisoni, Giovanni B.; Linazasoro, Gurutz; de Leon, Mony J.; van der Flier, Wiesje M.; Scheltens, Philip; Blennow, Kaj; Shaw, Leslie M.

    2015-01-01

    In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer’s disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40–84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer’s disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype

  19. Possibilities of immunocytochemical phenotyping of cells in cerebrospinal fluid while children’s bacterial meningitis

    Directory of Open Access Journals (Sweden)

    V. E. Karev

    2013-01-01

    Full Text Available Comparative dynamic clinical and immunomorphological researches of children’s cerebrospinal fluid were made during bacterial purulent meningitis (caused by Neisseria meningitis, Streptococcus pneumoniae, Haemophilus influenza. Regularities connected with presence of CD3 lymphocytes were discovered. They depended on etiology and phase of disease. Children with meningococcal meningitis, pneumococcal meningitis or hemophilic meningitis had different levels of CD3 lymphocytes in cerebrospinal fluid while different phases of disease.

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

    Science.gov (United States)

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

    2016-09-01

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

  1. Determination of specific IgE in pericardial and cerebrospinal fluids in forensic casework.

    Science.gov (United States)

    Tran, Lara; Astengo, Benedicta; Palmiere, Cristian

    2016-10-01

    The aim of this study was to characterize total and specific IgE distribution in postmortem serum as well as pericardial and cerebrospinal fluid samples and evaluate the diagnostic usefulness of total and specific IgE determination in pericardial and cerebrospinal fluids in the forensic setting. Three groups were investigated (non-allergic deaths in non-atopic individuals, fatal allergic anaphylaxis deaths and non-allergic deaths in individuals without medical records). In the first group (non-allergic deaths in non-atopic individuals), total IgE concentrations in postmortem serum from femoral blood, pericardial and cerebrospinal fluids were lower than 40, 32 and 11kU/l, respectively. No specific IgE were identified in any of the sampled fluids. In the second group (fatal allergic anaphylaxis deaths), total IgE concentrations in postmortem serum from femoral blood ranged from 139kU/l to 818kU/l, in pericardial fluid from 89kU/l to 622kU/l and in cerebrospinal fluid from 4kU/l to 11kU/l. A positive Phadiatop ® test and specific IgE antibodies >0.35kU/l were found exclusively in postmortem serum from femoral blood and pericardial fluid. In the third group (non-allergic deaths in individuals without medical records, possibly including atopic individuals), total IgE concentrations ranged from 42kU/l to 516kU/l in postmortem serum from femoral blood, from 34kU/l to 417kU/l in pericardial fluid and from 3kU/l to 12kU/l in cerebrospinal fluid. A positive Phadiatop ® test and specific IgE antibodies >0.35kU/l were found exclusively in postmortem serum from femoral blood and pericardial fluid. These results seem to suggest that total and specific IgE may be measured in postmortem serum from femoral blood and pericardial fluid to estimate total and specific IgE titers at the time of death. Conversely, cerebrospinal fluid total and specific IgE measurement in suspected IgE mediated fatal anaphylaxis cases is of no value for diagnostic purposes. Copyright © 2016 Elsevier

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Jørgensen, Ole Steen

    1988-01-01

    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...... fluid, both compared to cisternal fluid. Whereas prealbumin was found evenly distributed in CSF, albumin was relatively enriched in lumbar fluid. The concentrations of NCAM-sol and prealbumin were measured in lumbar CSF from psychiatric patients. Prealbumin was increased 7.2% and NCAM-sol was decreased...

  4. Quality assurance for cerebrospinal fluid protein analysis : International consensus by an Internet-based group discussion

    NARCIS (Netherlands)

    Reiber, H; Thompson, EJ; Grimsley, G; Bernardi, G; Adam, P; de Almeida, SM; Fredman, P; Keir, G; Liblau, R; Menna-Barreto, MM; Maria, JS; Seres, E; Sindic, CJM; Teelken, A; Trendelenburg, C; Trojano, M; van Antwerpen, MP; Verbeek, MM; Lammers, M.

    2003-01-01

    A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This

  5. Quality assurance for cerebrospinal fluid protein analysis: international consensus by an Internet-based group discussion.

    NARCIS (Netherlands)

    Reiber, H.; Thompson, E.J.; Grimsley, G.; Bernardi, G.; Adam, P.; Monteiro de Almeida, S.; Fredman, P.; Keir, G.; Lammers, M.W; Liblau, R.; Menna-Barreto, M.; Sa, M.J.; Seres, E.; Sindic, C.J.; Teelken, A.W.; Trendelenburg, C.; Trojano, M.; Antwerpen, M.P. van; Verbeek, M.M.

    2003-01-01

    A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Ostergaard, C; Johansen, JS; Benfield, Thomas

    2002-01-01

    cerebrospinal fluid (CSF) samples taken on admission from patients suspected of having meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were significantly higher in patients with purulent meningitis (median...

  8. Spontaneous Cerebrospinal Fluid Otorrhea from a Persistent Tympanomeningeal Fissure Presenting as Recurrent Serous Otitis Media

    DEFF Research Database (Denmark)

    Zakaryan, Arman; Poulsgaard, Lars; Hollander, Camilla

    2015-01-01

    We describe spontaneous cerebrospinal fluid (CSF) otorrhea through a patent tympanomeningeal (Hyrtl) fissure presenting as recurrent serous otitis media. The CSF leak was observed when a drain was placed through the tympanic membrane by an otologist. The diagnosis was then confirmed by computed...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  10. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force

    DEFF Research Database (Denmark)

    Deisenhammer, F; Bartos, A; Egg, R

    2006-01-01

    A great variety of neurological diseases require investigation of cerebrospinal fluid (CSF) to prove the diagnosis or to rule out relevant differential diagnoses. The objectives were to evaluate the theoretical background and provide guidelines for clinical use in routine CSF analysis including...

  11. Pre-analytical factors influencing the stability of cerebrospinal fluid proteins

    DEFF Research Database (Denmark)

    Simonsen, Anja H; Bahl, Justyna M C; Danborg, Pia B

    2013-01-01

    Cerebrospinal fluid (CSF) is a potential source for new biomarkers due to its proximity to the brain. This study aimed to clarify the stability of the CSF proteome when undergoing pre-analytical factors. We investigated the effects of repeated freeze/thaw cycles, protease inhibitors and delayed...

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

    DEFF Research Database (Denmark)

    Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan

    2011-01-01

    The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories...

  13. Alfa-synuclein in cerebrospinal fluid as a possible biomarker for Parkinson disease

    DEFF Research Database (Denmark)

    Juul Bøgelund Hansen, Morten; Brandslund, Ivan; Dalsgaard Lund, Erik

    - synuclein oligomer the in the cerebrospinal fluid can be used as a biomarker for diagnosing PD. Design A total of 36 patients diagnosed with PD and 36 controls matched in sex and age were included in this study. The PD patients were classified according to the Hoehn-Yahr classification. The concentration...

  14. Acetazolamide lowers intracranial pressure and modulates the cerebrospinal fluid secretion pathway in healthy rats

    DEFF Research Database (Denmark)

    Uldall, Maria; Botfield, Hannah; Jansen-Olesen, Inger

    2017-01-01

    Acetazolamide is one of the most widely used drugs for lowering intracranial pressure (ICP) and is believed to reduce cerebrospinal fluid (CSF) secretion via its action on the choroid plexus (CP). In the CP the main driving force for CSF secretion is primarily active transport of Na...

  15. Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Khorooshi, Reza; Lillevang, Søren T

    2013-01-01

    The specificity and potential pathogenicity of autoantibodies vary between neurological diseases. It is often unclear whether their detection in cerebrospinal fluid (CSF) is a consequence or a cause of pathology. The goal was to test whether administration of brain-specific antibodies into CSF...

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    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...

  17. Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis

    DEFF Research Database (Denmark)

    Teunissen, Charlotte; Menge, Til; Altintas, Ayse

    2013-01-01

    The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus...

  18. miRNA profiles in cerebrospinal fluid from patients with central hypersomnias

    DEFF Research Database (Denmark)

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine

    2014-01-01

    addressed whether miRNA levels are altered in the cerebrospinal fluid (CSF) of patients with central hypersomnias. We conducted high-throughput analyses of miRNAs in CSF from patients using quantitative real-time polymerase chain reaction panels. We identified 13, 9, and 11 miRNAs with a more than two...

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

    DEFF Research Database (Denmark)

    Gideon, P; Ståhlberg, F; Thomsen, C

    1994-01-01

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

  20. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B

    2010-01-01

    -acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging...

  2. Detection of Neisseria meningitidis in cerebrospinal fluid using a multiplex PCR and the Luminex detection technology

    DEFF Research Database (Denmark)

    Møller, Jens Kjølseth

    2012-01-01

    pathogens most frequently found in the cerebrospinal fluid of patients. The Luminex suspension array system uniquely combines flow cytometry, microspheres, laser technology, digital signal processing, and traditional chemistry. In this method, the reaction is carried out in one vessel, in which distinctly...

  3. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    DEFF Research Database (Denmark)

    De Vis, J B; Zwanenburg, J J; van der Kleij, L A

    2016-01-01

    OBJECTIVES: To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. METHODS: Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  5. Cerebrospinal fluid findings in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathies

    DEFF Research Database (Denmark)

    Illes, Zsolt; Blaabjerg, Morten

    2017-01-01

    The classic immunologic alteration of the cerebrospinal fluid (CSF) in Guillain-Barré syndrome (GBS), albuminocytologic dissociation, has been known since the original paper by Guillain, Barré, and Strohl. Albuminocytologic dissociation has been also described in other forms of the GBS spectrum...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Støvring, Birgitte; Vang, Ole; Christiansen, Michael

    2005-01-01

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

  8. Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment

    DEFF Research Database (Denmark)

    Herukka, Sanna-Kaisa; Simonsen, Anja Hviid; Andreasen, Niels

    2017-01-01

    This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive...

  9. Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma

    DEFF Research Database (Denmark)

    Hansen, P B; Kjeldsen, L; Dalhoff, K

    1992-01-01

    Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic...

  10. Cerebrospinal fluid pleocytosis in infectious and noninfectious central nervous system disease

    DEFF Research Database (Denmark)

    Baunbæk Egelund, Gertrud; Ertner, Gideon; Langholz Kristensen, Kristina

    2017-01-01

    Cerebrospinal fluid (CSF) analysis is the most important tool for assessing central nervous system (CNS) disease. An elevated CSF leukocyte count rarely provides the final diagnosis, but is almost always an indicator of inflammation within the CNS.The present study investigated the variety...

  11. Quantitative proteomics and metabolomics analysis of normal human cerebrospinal fluid samples

    NARCIS (Netherlands)

    Stoop, M.P.; Coulier, L.; Rosenling, T.; Shi, S.; Smolinska, A.M.; Buydens, L.; Ampt, K.; Stingl, C.; Dane, A.; Muilwijk, B.; Luitwieler, R.L.; Sillevis Smitt, P.A.E.; Hintzen, R.Q.; Bischoff, R.; Wijmenga, S.S.; Hankemeier, T.; Gool, A.J. van; Luider, T.M.

    2010-01-01

    The analysis of cerebrospinal fluid (CSF) is used in biomarker discovery studies for various neurodegenerative central nervous system (CNS) disorders. However, little is known about variation of CSF proteins and metabolites between patients without neurological disorders. A baseline for a large

  12. Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

    NARCIS (Netherlands)

    Kester, M.I.; Teunissen, C.E.; Crimmins, D.L.; Herries, E.M.; Ladenson, J.H.; Scheltens, P.; van der Flier, W.M.; Morris, J.C.; Holtzman, D.M.; Fagan, A.M.

    2015-01-01

    IMPORTANCE: Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE: To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of

  13. Concordance Between Cerebrospinal Fluid Biomarkers and [C-11] PIB PET in a Memory Clinic Cohort

    NARCIS (Netherlands)

    Zwan, M.D.; van Harten, A.C.; Ossenkoppele, R.; Bouwman, F.H.; Teunissen, C.; Adriaanse, S.M.; Lammertsma, A.A.; Scheltens, P.; van Berckel, B.N.M.; van der Flier, W.M.

    2014-01-01

    BACKGROUND: Two approaches are available for measuring Alzheimer's disease (AD) pathology in vivo. Biomarkers in cerebrospinal fluid (CSF) include amyloid-β1-42 (Aβ42) and tau. Furthermore, amyloid deposition can be visualized using positron emission tomography (PET) and [11C]Pittsburgh compound-B

  14. Cerebrospinal fluid biomarkers of neurodegeneration are decreased or normal in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Pedersen, Lars Østergaard; Bahl, Justyna Maria Czarna

    2017-01-01

    OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. METHODS: Twenty-one patients with central...... that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in CNS....

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

    Directory of Open Access Journals (Sweden)

    Sofia Temudo Duarte

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

  16. Profiling and Identification of Cerebrospinal Fluid Proteins in a Rat EAE Model of Multiple Sclerosis

    NARCIS (Netherlands)

    Rosenling, Therese; Stoop, Marcel P.; Attali, Amos; van Aken, Hans; Suidgeest, Ernst; Christin, Christin; Stingl, Christoph; Suits, Frank; Horvatovich, Peter; Hintzen, Rogier Q.; Tuinstra, Tinka; Bischoff, Rainer; Luider, Theo M.

    The experimental autoimmune encephalomyelitis (EAR) model resembles certain aspects of multiple sclerosis (MScl), with common features such as motor dysfunction, axonal degradation, and infiltration of T-cells. We studied the cerebrospinal fluid (CSF) proteome in the EAE rat model to identify

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

    International Nuclear Information System (INIS)

    Toczylowska, B.; Jozwik, A.; Kierul, K.; Matysiak, Z.; Sidor, M.; Wojcik, J.

    1999-01-01

    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

  18. Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis

    NARCIS (Netherlands)

    Zwijnenburg, Petra J. G.; de Bie, Henrica M. A.; Roord, John J.; van der Poll, Tom; van Furth, A. Marceline

    2003-01-01

    CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinal fluid (CSF) of

  19. Decline of HIV antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine

    NARCIS (Netherlands)

    de Gans, J.; Lange, J. M.; Derix, M. M.; de Wolf, F.; Eeftinck Schattenkerk, J. K.; Danner, S. A.; Ongerboer de Visser, B. W.; Cload, P.; Goudsmit, J.

    1988-01-01

    Six HIV-antigenaemic patients with AIDS or AIDS-related complex were studied to assess the effect of treatment with low-dose zidovudine (250 mg) in 6-hourly doses on HIV antigen (HIV-Ag) levels in cerebrospinal fluid (CSF). HIV-Ag was detected in CSF of three patients before treatment. These

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

    Directory of Open Access Journals (Sweden)

    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

  1. An Improved Method for Collection of Cerebrospinal Fluid from Anesthetized Mice

    DEFF Research Database (Denmark)

    Lim, Nastasia K-H; Moestrup, Visse Theresia Skov; Zhang, Xiao

    2017-01-01

    The cerebrospinal fluid (CSF) is a valuable body fluid for analysis in neuroscience research. It is one of the fluids in closest contact with the central nervous system and thus, can be used to analyze the diseased state of the brain or spinal cord without directly accessing these tissues. However...... during CSF extraction. Thus, the brain and spinal cord are not affected with this technique and remain intact. With greater CSF sample collection and purity, more analyses can be used with this fluid to further aid neuroscience research and better understand diseases affecting the brain and spinal cord....

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

    DEFF Research Database (Denmark)

    Cohen, Benjamin; Voorhees, Abram; Vedel, Søren

    2009-01-01

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

  3. Non-traumatic cerebrospinal fluid rhinorrhea: diagnosis and management

    International Nuclear Information System (INIS)

    Al-Sebeih, Khalid; Karagiozov, Kostadin; Elbeltagi, Kostadin; Al-Qattan, Fuad

    2004-01-01

    Although the majority of cerebrospinal (CSF) fistulas in the anterior skull base are traumatic in nature, the minority is non-traumatic or primary. Non-traumatic CSF leak can be a diagnostic and treatment challenge. We describe the diagnosis, modified methods of localization, and surgical repair of a series of nine patients who presented with non-traumatic CSF rhinorrhea and were managed between July 2000 and October 2002. Coronal CT scans were obtained for all patients. Additional radiological tests were also done. Eight patients we managed via an endoscopic approach and one patient through an intracranial approach. The RI/T2-FLAIR test was used for localization of the site of leak. The test confirmed the site of CSF leak in six patients. The test confirmed the site of CSF leak in 6 patients. Successful repair of CSF rhinorrhea was achieved in 7 of 8 patients with a single endoscopic procedure; one patient required two procedures after a re-leak 18 months following the first repair. Non-traumatic CSF rhinorrhea is a relatively rare condition and occurs secondary to different etiologies. Among multiple techniques available for localization, MRI/FLAIR is effective, but requires further evaluation and polishing. In the absence of large skull base lesions or tumor, endoscopic repair of CSF fistula carries a high success rate with a high margin of safety and low morbidity rate. (author)

  4. Cerebrospinal fluid humoral immunity in the differential diagnosis of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Evanthia Bernitsas

    Full Text Available The diagnostic accuracy of cerebrospinal fluid oligoclonal bands (CSF-OCB detected by isoelectric focusing (IEF in patients with multiple sclerosis (MS was evaluated in our study.Three hundred and twenty-one patients with MS and other central nervous system (CNS immune mediated disorders were assessed (CIMD. Cerebrospinal fluid and matched serum samples were examined for the presence of OCB by IEF-IB (isoelectric focusing with immunoblotting.Isolated oligoclonal bands (ISO-OCB were the only predictor of MS diagnosis independent of age, gender and CSF-OCB. ISO-OCB ≥ 3.5 detected by IEF yielded a sensitivity of 98% and specificity of 87% in distinguishing MS from MS mimickers.For the neurologist, a score of ≥ 4 ISO-OCB supports the diagnosis of MS. On the other hand, ISO-OCB ≤3 favors CIMD. Further studies with larger population samples are warranted to confirm these findings.

  5. Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer’s Disease Brain

    Science.gov (United States)

    Rueli, Rachel H.L.H.; Parubrub, Arlene C.; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane H.; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

    2015-01-01

    Subjects with Alzheimer’s disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium. PMID:25298198

  6. More advanced Alzheimer's disease may be associated with a decrease in cerebrospinal fluid pressure

    Directory of Open Access Journals (Sweden)

    De Deyn Peter

    2009-11-01

    Full Text Available Abstract In a recent article, elevated cerebrospinal fluid pressure (CSFP consistent with very early normal pressure hydrocephalus (NPH, was found in a small subset of Alzheimer's disease (AD patients (possible AD-NPH hybrids enrolled in a clinical trial for chronic low-flow cerebrospinal fluid drainage. Also in the same study, was another interesting finding that merits further discussion: a substantial proportion of AD patients had very low CSFP. Based on the characteristics of these subjects, we hypothesize that more advanced AD may be associated with a decrease in CSFP. Reduced CSFP among a group of AD patients could provide a clue towards a better understanding of the high rate of comorbidity reported between AD and glaucoma since it has been shown that mean CSFP is lower in subjects with primary open-angle glaucoma. This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage.

  7. Monoamine neurotransmitter disorders--clinical advances and future perspectives.

    Science.gov (United States)

    Ng, Joanne; Papandreou, Apostolos; Heales, Simon J; Kurian, Manju A

    2015-10-01

    The monoamine neurotransmitter disorders are important genetic syndromes that cause disturbances in catecholamine (dopamine, noradrenaline and adrenaline) and serotonin homeostasis. These disorders result in aberrant monoamine synthesis, metabolism and transport. The clinical phenotypes are predominantly neurological, and symptoms resemble other childhood neurological disorders, such as dystonic or dyskinetic cerebral palsy, hypoxic ischaemic encephalopathy and movement disorders. As a consequence, monoamine neurotransmitter disorders are under-recognized and often misdiagnosed. The diagnosis of monoamine neurotransmitter disorders requires detailed clinical assessment, cerebrospinal fluid neurotransmitter analysis and further supportive diagnostic investigations. Prompt and accurate diagnosis of neurotransmitter disorders is paramount, as many are responsive to treatment. The treatment is usually mechanism-based, with the aim to reverse disturbances of monoamine synthesis and/or metabolism. Therapeutic intervention can lead to complete resolution of motor symptoms in some conditions, and considerably improve quality of life in others. In this Review, we discuss the clinical features, diagnosis and management of monoamine neurotransmitter disorders, and consider novel concepts, the latest advances in research and future prospects for therapy.

  8. Correlation between leukocyte aggregation score of cerebrospinal fluid and bacterial meningitis in children

    OpenAIRE

    Meitha PE Togas; Nurhayati Masloman

    2016-01-01

    Background Bacterial meningitis is one of life-threatening dis- eases and carries a risk of sequelae in affected children. In terms of cost and rapid differentiation between bacterial and non-bacte- rial meningitis, several tests have been proposed. Objective This study aimed to determine the use of leukocyte aggregation score (LAS) of cerebrospinal fluid (CSF) in diagnos- ing bacterial meningitis. Methods A prospective analytic study was done from October 2001 to July...

  9. The Relation of Cerebrospinal Fluid Nitric Oxide Levels to Prognosis and Differential Diagnosis of Meningitis

    OpenAIRE

    ÇETİN, Kasım

    2014-01-01

    This study was designed to investigate the role of nitric oxide (NO) in the differential diagnosis of bacterial, tuberculous and viral meningitis, and the relation between cerebrospinal fluid (CSF) NO levels and meningitis prognosis. Twenty patients with bacterial meningitis, 9 with tuberculous meningitis, 11 with viral meningitis/meningoencephalitis and 21 control patients were included in the study. CSF NO levels were investigated by measuring the levels of nitrite with a colorimetric test...

  10. Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid

    OpenAIRE

    Mason, Shayne; Reinecke, Carolus J.; Kulik, Willem; van Cruchten, Arno; Solomons, Regan; van Furth, A. Marceline Tutu

    2016-01-01

    Background The defining feature of the cerebrospinal fluid (CSF) collected from infants and children with tuberculous meningitis (TBM), derived from an earlier untargeted nuclear magnetic resonance (NMR) metabolomics study, was highly elevated lactic acid. Undetermined was the contribution from host response (L-lactic acid) or of microbial origin (D-lactic acid), which was set out to be determined in this study. Methods In this follow-up study, we used targeted ultra-performance liquid chroma...

  11. Post-neurosurgical meningitis: Management of cerebrospinal fluid drainage catheters influences the evolution of infection

    OpenAIRE

    Laura Soavi; Manuela Rosina; Roberto Stefini; Alessia Fratianni; Barbara Cadeo; Silvia Magri; Nicola Latronico; Marco Fontanella; Liana Signorini

    2016-01-01

    Background: In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. Methods: This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999...

  12. Spontaneous recovery of post-traumatic cerebrospinal fluid rhinorrhea following meningitis: A case report

    OpenAIRE

    Citisli, Veli; Kocaoglu, Murat; Necan, Ceyda; İbrahimoglu, Muhammet; Celiker, Özkan; Baykara, Eyüp; Ozdemir, Mevci; Acar, Feridun; Coskun, Mehmet Erdal

    2015-01-01

    The aim of the present report was to present the patient with an anterior cranial base fracture who developed post-traumatic cerebrospinal fluid rhinorrhea, which recovered after onset of meningitis complication. A 26-year-old male patient who had a traffic accident one week ago was sent to our clinic because of his rhinorrhea persisting for 4 days. On cranial computed tomography, fracture of the left frontal skull base and sinus walls, a fracture line on temporal bone, parenchymal bleeding i...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-15

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

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

    Science.gov (United States)

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

    2016-02-01

    Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose. Copyright © 2015. Published by Elsevier Ltd.

  15. Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children

    OpenAIRE

    Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

    2017-01-01

    ABSTRACT Objective To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. Methods A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bact...

  16. Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children

    OpenAIRE

    Nazir, Mudasir; Wani, Wasim Ahmad; Malik, Muzaffar Ahmad; Mir, Mohd Rafiq; Ashraf, Younis; Kawoosa, Khalid; Ali, Syed Wajid

    2018-01-01

    Abstract Objective: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Methods: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. Results: At a cut-off value of 3 mmol/L, CSF lactate had a sensitivit...

  17. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis.

    Science.gov (United States)

    Kreye, Jakob; Wenke, Nina K; Chayka, Mariya; Leubner, Jonas; Murugan, Rajagopal; Maier, Nikolaus; Jurek, Betty; Ly, Lam-Thanh; Brandl, Doreen; Rost, Benjamin R; Stumpf, Alexander; Schulz, Paulina; Radbruch, Helena; Hauser, Anja E; Pache, Florence; Meisel, Andreas; Harms, Lutz; Paul, Friedemann; Dirnagl, Ulrich; Garner, Craig; Schmitz, Dietmar; Wardemann, Hedda; Prüss, Harald

    2016-10-01

    SEE ZEKERIDOU AND LENNON DOI101093/AWW213 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesias, and seizures. Little is known about the cerebrospinal fluid autoantibody repertoire. Antibodies against the NR1 subunit of the NMDAR are thought to be pathogenic; however, direct proof is lacking as previous experiments could not distinguish the contribution of further anti-neuronal antibodies. Using single cell cloning of full-length immunoglobulin heavy and light chain genes, we generated a panel of recombinant monoclonal NR1 antibodies from cerebrospinal fluid memory B cells and antibody secreting cells of NMDAR encephalitis patients. Cells typically carried somatically mutated immunoglobulin genes and had undergone class-switching to immunoglobulin G, clonally expanded cells carried identical somatic hypermutation patterns. A fraction of NR1 antibodies were non-mutated, thus resembling 'naturally occurring antibodies' and indicating that tolerance induction against NMDAR was incomplete and somatic hypermutation not essential for functional antibodies. However, only a small percentage of cerebrospinal fluid-derived antibodies reacted against NR1. Instead, nearly all further antibodies bound specifically to diverse brain-expressed epitopes including neuronal surfaces, suggesting that a broad repertoire of antibody-secreting cells enrich in the central nervous system during encephalitis. Our functional data using primary hippocampal neurons indicate that human cerebrospinal fluid-derived monoclonal NR1 antibodies alone are sufficient to cause neuronal surface receptor downregulation and subsequent impairment of NMDAR-mediated currents, thus providing ultimate proof of antibody pathogenicity. The observed formation of immunological memory might be relevant for clinical relapses. © The Author (2016). Published by Oxford University Press on

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

    Energy Technology Data Exchange (ETDEWEB)

    Otto, H.J. (Medizinische Akademie, Magdeburg (German Democratic Republic). Radiologische Klinik); Koch, R.D.; Krause, P. (Medizinische Akademie, Magdeburg (German Democratic Republic). Nervenklinik)

    1983-06-01

    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.

  19. Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis.

    Science.gov (United States)

    García-Hernández, Pablo; Prieto, Belén; Martínez-Morillo, Eduardo; Rodríguez, Verónica; Álvarez, Francisco V

    2016-01-01

    Microbiological culture of cerebrospinal fluid is the gold standard to differentiate between aseptic and bacterial meningitis, but this method has low sensitivity. A fast and reliable new marker would be of interest in clinical practice. Interleukin-6, secreted by T cells in response to meningeal pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a marker of acute meningitis. A total of 150 cerebrospinal fluid samples were analysed by an electrochemiluminescence method, selected according to patient diagnosis: (a) bacterial meningitis confirmed by positive culture (n = 26); (b) bacterial meningitis with negative culture or not performed (n = 15); (c) viral meningitis confirmed by polymerase chain reaction or immunoglobulin G determination (n = 23); (d) viral meningitis with polymerase chain reaction negative or not performed (n = 42); and (e) controls (n = 44). Cerebrospinal fluid interleukin-6 concentration showed significant differences between all pathologic groups and the control group (P meningitis, interleukin-6 showed an area under the curve of 0.937 (95% confidence intervals: 0.895-0.978), significantly higher than those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5% sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6% sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis. Interleukin-6 measured by electrochemiluminescence method is a promising marker for early differentiation between aseptic and bacterial meningitis. More studies are needed to validate clinical implications for future practice in an emergency laboratory. © The Author(s) 2015.

  20. Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

    OpenAIRE

    Martin‐Vaquero, P.; da Costa, R.C.; Moore, S.A.; Gross, A.C.; Eubank, T.D.

    2014-01-01

    Background Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs. Hypothesis/Objectives That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM‐affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)‐6 and monocyte chemoattractant protein‐1/chemokine ligand 2 (MCP‐...

  1. Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: comparison of primer sets for Cryptococcus neoformans and Cryptococcus gattii species complex

    Directory of Open Access Journals (Sweden)

    Marilena dos Anjos Martins

    2015-01-01

    Conclusions: These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis.

  2. Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures.

    NARCIS (Netherlands)

    Bicanic, T.; Brouwer, A.E.; Meintjes, G.; Rebe, K.; Limmathurotsakul, D.; Chierakul, W.; Teparrakkul, P.; Loyse, A.; White, N.J.; Wood, R.; Jaffar, S.; Harrison, T.

    2009-01-01

    OBJECTIVES: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune

  3. [1st case of eosinophilic meningitis in Ivory Coat with the presence of a Parastrongylus sp. in the cerebrospinal fluid].

    Science.gov (United States)

    Nozais, J P; Moreau, J; Morlier, G; Kouame, J; Doucet, J

    1980-01-01

    The authors report the first observation, in West Africa, of eosinophilic meningitis in an ivorian child who ingested raw Achatina sp. The presence of a Parastrongylus. sp. in the cerebrospinal fluid was detected.

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

    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

  5. D-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid homovanillic acid concentrations in healthy Caucasians

    DEFF Research Database (Denmark)

    Andreou, Dimitrios; Saetre, Peter; Werge, Thomas

    2012-01-01

    in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn...

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

    International Nuclear Information System (INIS)

    Lee, Sangwook; Silajdžić, Edina; Björkqvist, Maria; Yang, Hon; Kim, Soyon; Jeong, Ok Chan; Hansson, Oskar; Laurell, Thomas

    2014-01-01

    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)

  7. Cerebrospinal fluid otorrhea and pseudomonal meningitis in a child with Mondini dysplasia: case report.

    Science.gov (United States)

    Hernandez, R Nick; Changa, Abhinav R; Bassani, Luigi; Jyung, Robert W; Liu, James K

    2015-09-01

    Mondini dysplasia is a rare congenital inner ear malformation that presents with abnormal cochlear development with accompanied vestibular dilation and vestibular aqueduct enlargement. This dysfunctional anatomy provides the potential for sensorineural hearing deficits, cerebrospinal fluid leaks, and severe cases of recurrent meningitis. We present the case of a child with Mondini dysplasia who presented with unilateral hearing loss and cerebrospinal fluid (CSF) otorrhea that was surgically repaired through a combined middle fossa/transmeatal middle ear approach to alleviate any recurrence of infection and cerebrospinal fluid otorrhea. Postoperatively, the patient remained neurologically stable without any further CSF leakage. CSF cultures revealed a Pseudomonas aeruginosa infection, a rare occurrence within the context of Mondini dysplasia. Retrograde bacterial spread from the external ear canal into the CSF space has been theorized as the possible pathogenesis of the resulting meningitis. The patient was successfully treated with intravenous antibiotics without any neurologic complications. Although Mondini dysplasia is a rare malformation, the life-threatening sequelae of meningitis that can result from the dysfunctional anatomy makes it a condition that requires elevated clinical vigilance, especially when considering children with hearing loss associated with recurrent meningitis, otorrhea, or rhinorrhea.

  8. Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease—From Brain Starch to Bench and Bedside

    Directory of Open Access Journals (Sweden)

    Matthias Pawlowski

    2017-07-01

    Full Text Available Alzheimer’s disease is the most common cause of dementia. Over the last three decades, research has advanced dramatically and provided a detailed understanding of the molecular events underlying the pathogenesis of Alzheimer’s disease. In parallel, assays for the detection of biomarkers that reflect the typical Alzheimer’s disease-associated pathology have been developed and validated in myriads of clinical studies. Such biomarkers complement clinical diagnosis and improve diagnostic accuracy. The use of biomarkers will become even more important with the advent of disease-modifying therapies. Such therapies will likely be most beneficial when administered early in the disease course. Here, we summarise the development of the core Alzheimer’s disease cerebrospinal fluid biomarkers: amyloid-β and tau. We provide an overview of their role in cellular physiology and Alzheimer’s disease pathology, and embed their development as cerebrospinal fluid biomarkers into the historical context of Alzheimer’s disease research. Finally, we summarise recommendations for their use in clinical practice, and outline perspectives for novel cerebrospinal fluid candidate biomarkers.

  9. Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children

    Science.gov (United States)

    Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

    2017-01-01

    ABSTRACT Objective To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. Methods A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. Results The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. Conclusion Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone. PMID:28767914

  10. Application of Control Volume Analysis to Cerebrospinal Fluid Dynamics

    Science.gov (United States)

    Wei, Timothy; Cohen, Benjamin; Anor, Tomer; Madsen, Joseph

    2011-11-01

    Hydrocephalus is among the most common birth defects and may not be prevented nor cured. Afflicted individuals face serious issues, which at present are too complicated and not well enough understood to treat via systematic therapies. This talk outlines the framework and application of a control volume methodology to clinical Phase Contrast MRI data. Specifically, integral control volume analysis utilizes a fundamental, fluid dynamics methodology to quantify intracranial dynamics within a precise, direct, and physically meaningful framework. A chronically shunted, hydrocephalic patient in need of a revision procedure was used as an in vivo case study. Magnetic resonance velocity measurements within the patient's aqueduct were obtained in four biomedical state and were analyzed using the methods presented in this dissertation. Pressure force estimates were obtained, showing distinct differences in amplitude, phase, and waveform shape for different intracranial states within the same individual. Thoughts on the physiological and diagnostic research and development implications/opportunities will be presented.

  11. Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report.

    Science.gov (United States)

    Engelmann, Ilka; Nasser, Hala; Belmiloudi, Soufien; Le Guern, Rémi; Dewilde, Anny; Vallée, Louis; Hober, Didier

    2013-06-01

    A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare complication of infectious mononucleosis. The severe clinical picture and the marked neuroimaging changes were in contrast with mild cerebrospinal fluid abnormalities: leukocyte count was normal and protein level was only slightly elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain reaction. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection

    OpenAIRE

    Hopkins Stephen J; McMahon Catherine J; Singh Navneet; Galea James; Hoadley Margaret; Scarth Sylvia; Patel Hiren; Vail Andy; Hulme Sharon; Rothwell Nancy J; King Andrew T; Tyrrell Pippa J

    2012-01-01

    Abstract Background Cytokines and cytokine receptor concentrations increase in plasma and cerebrospinal fluid (CSF) of patients following subarachnoid haemorrhage (SAH). The relationship between plasma and CSF cytokines, and factors affecting this, are not clear. Methods To help define the relationship, paired plasma and cerebrospinal fluid (CSF) samples were collected from patients subject to ventriculostomy. Concentrations of key inflammatory cytokines, interleukin (IL)-1ß, IL-1 receptor an...

  13. NITRIC OXIDE ACTIVITY OF NEUTROPHIL IN BLOOD AND CEREBROSPINAL FLUID OF THE CHILDREN WITH BACTERIAL AND VIRAL MENINGITIS

    Directory of Open Access Journals (Sweden)

    V. P. Molochniy

    2014-01-01

    Full Text Available The article presents the results of study of nitric oxide activity of neutrophil leucocytic and freeradical processes in blood and cerebrospinal fluid of the children with bacterial and viral meningitison the acute period diseases. The peculiarities or activity of freeradical processes and nitric oxide of cerebrospinal fluid with bacterial meningitis in acute period diseases and activities of studies of ferments with the health children. 

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

    DEFF Research Database (Denmark)

    Jørgensen, Ole Steen

    1988-01-01

    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 ventricula...... 15.1% in depressed patients. The changes were partially normalized during recovery from the depression. The findings can be explained by hypothesizing that endogenous depression is associated with an increased choroid plexus activity and CSF production....

  15. Numerical simulation of cerebrospinal fluid hydrodynamics in the healing process of hydrocephalus patients

    Science.gov (United States)

    Gholampour, S.; Fatouraee, N.; Seddighi, A. S.; Seddighi, A.

    2017-05-01

    Three-dimensional computational models of the cerebrospinal fluid (CSF) flow and brain tissue are presented for evaluation of their hydrodynamic conditions before and after shunting for seven patients with non-communicating hydrocephalus. One healthy subject is also modeled to compare deviated patients data to normal conditions. The fluid-solid interaction simulation shows the CSF mean pressure and pressure amplitude (the superior index for evaluation of non-communicating hydrocephalus) in patients at a greater point than those in the healthy subject by 5.3 and 2 times, respectively.

  16. Relationship between cerebrospinal fluid concentrations of orexin A/hypocretin-1 and body composition in humans.

    Science.gov (United States)

    Santiago, João C P; Otto, Markus; Kern, Werner; Baier, Paul Christian; Hallschmid, Manfred

    2018-02-19

    The hypothalamic neuropeptide orexin A (hypocretin-1) is a key signal in sleep/wake regulation and promotes food intake. We investigated the relationship between cerebrospinal fluid orexin A concentrations and body composition in non-narcoleptic human subjects with a wide range of body weight to gain insight into the role of orexin A in human metabolism. We collected cerebrospinal fluid and blood samples and measured body composition by bioelectric impedance analysis in 36 subjects (16 women and 20 men) with body mass indices between 16.24 and 38.10 kg/m 2 and an age range of 19-80 years. Bivariate Pearson correlations and stepwise multiple regressions were calculated to determine associations between orexin A and body composition as well as biometric variables. Concentrations of orexin A in cerebrospinal fluid averaged 315.6 ± 6.0 pg/ml, were comparable between sexes (p > 0.15) and unrelated to age (p > 0.66); they appeared slightly reduced in overweight/obese compared to normal-weight subjects (p = .07). Orexin A concentrations decreased with body weight (r = -0.38, p = .0229) and fat-free mass (r = -0.39, p = .0173) but were not linked to body fat mass (p > 0.24). They were inversely related to total body water (r = -0.39, p = .0174) as well as intracellular (r = -0.41, p = .0139) and extracellular water (r = -0.35, p = .0341). Intracellular water was the only factor independently associated with cerebrospinal fluid orexin A concentrations (p = .0139). We conclude that cerebrospinal fluid orexin A concentrations do not display associations with body adiposity, but are inversely related to intracellular water content. These cross-sectional findings suggest a link between orexin A signaling and the regulation of water homeostasis in humans. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Review on metal speciation analysis in cerebrospinal fluid-current methods and results: a review.

    Science.gov (United States)

    Michalke, Bernhard; Nischwitz, Volker

    2010-12-03

    The large number of patients suffering from neurodegenerative diseases like Alzheimer's disease and Parkinson's disease motivates many research groups worldwide to investigate pathogenic factors and molecular mechanisms of these diseases. Recent studies and reviews indicate that metals are involved in these neurodegenerative processes in case their homeostasis in the brain is disturbed. Important is that the focus of these recent studies is on essential metals like Fe, Cu, Zn and Mn, but not on the well-known neurotoxic metals like Hg and Pb. Key issues for understanding metal induced neurotoxic effects are the transport processes across the neural barriers, the metal binding forms (species) and their interactions with neuronal structures. Total metal concentrations in cerebrospinal fluid were published in several studies for controls and patients, but the amount of reliable data sets is not yet sufficient for clear definition of normal and elevated levels. The need for more detailed information on metal species in CSF is highlighted in this review. However, studies on element speciation analysis, that means identification and quantification of the various binding forms of metals in cerebrospinal fluid, are rare. The major reasons therefore are difficulties in accessing cerebrospinal fluid samples, the non-covalent nature of many metal species of interest and their rather low concentrations. In spite of this, several applications demonstrate the potential of hyphenated techniques as additional diagnostic tools for cerebrospinal fluid analysis. This review shows the importance of trace element analysis and more specifically of element speciation in cerebrospinal fluid for an improved understanding of pathologic mechanisms promoting neuro-degeneration. Respective analytical techniques are also highlighted. Additionally, biochemical assays for selected high molecular mass metal species are summarized and critically discussed. Moreover additional potential techniques

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

    Directory of Open Access Journals (Sweden)

    Smith Jennifer C

    2009-03-01

    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.

  19. Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.

    Science.gov (United States)

    Liu, Zhuo-Hao; Tu, Po-Hsun; Chen, Nan-Yu; Yip, Ping K; Bowes, Amy L; Lee, Cheng-Chi; Chan, She-Hung; Kung, Chua-Chi; Wang, Alvin Yi-Chou; Wu, Chieh-Tsai; Lee, Shih-Tseng

    2015-11-01

    The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients. Prospective, open-label, observational, cohort study. Neurosurgical ICU, Chang Gung Memorial Hospital. Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis. Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques. Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever. The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.

    1984-05-01

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)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.

  1. Genome-wide association study of prolactin levels in blood plasma and cerebrospinal fluid.

    Science.gov (United States)

    Staley, Lyndsay A; Ebbert, Mark T W; Parker, Sheradyn; Bailey, Matthew; Ridge, Perry G; Goate, Alison M; Kauwe, John S K

    2016-06-29

    Prolactin is a polypeptide hormone secreted by the anterior pituitary gland that plays an essential role in lactation, tissue growth, and suppressing apoptosis to increase cell survival. Prolactin serves as a key player in many life-critical processes, including immune system and reproduction. Prolactin is also found in multiple fluids throughout the body, including plasma and cerebrospinal fluid (CSF). In this study, we measured prolactin levels in both plasma and CSF, and performed a genome-wide association study. We then performed meta-analyses using METAL with a significance threshold of p prolactin levels in both biological fluids. Our efforts will help researchers understand how prolactin is regulated in both CSF and plasma, which could be beneficial in research for the immune system and reproduction.

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

    International Nuclear Information System (INIS)

    Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.

    1984-01-01

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and [ 14 C]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

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

    International Nuclear Information System (INIS)

    Oehninger Gatti, C.; Buzo Del Puerto, R.; Chouza Antelo, C.; Scotti Bianchi, C.; Cibils, D.; Alcantara Pelaez, J.; Gomez, A.; Heuguerot Oliveira, C.

    1994-01-01

    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) [es

  4. Exercise-induced Oxidative Shift of Lactate Dehydrogenase Isoforms in Cerebrospinal Fluid of Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Nasrin Sheikhhosseini

    2018-04-01

    Full Text Available Abstract Background: The aim of the present study was to investigate the effect of endurance training on the content of lactate dehydrogenase isoforms (LDHA and LDHB and isozymes in cerebrospinal fluid of male wistar rats. Materials and Methods: Seventeen animals (5 weeks old were randomly divided into two groups according their body weight: control (C; n = 9 and trained (T; n = 8. The animals from the T group were underwent a training program for 12 weeks (started at 20 m/min for 30 min and finished at 26 m/min for 60 min at the last week. Cerebrospinal fluid (CSF samples were collected from cisterna Magna 72 hours after the last exercise session. LDH Isoforms and isozymes were measured by ELISA and Electrophoresis techniques, and the comparisons between groups were evaluated by student t-test. Results: Both LDHA and LDHB isoforms were found in the CSF of the C group; LDH1 and LDH5 had the highest and lowest content, respectively. Following the twelve-week training protocol, LDHB (p<0.01, LDH1 (p<0.01, and LDH2 concentrations (p<0.01 were significantly increased in the T group compared with those from the C group and LDH3 concentrations (p<0.01 and LDHA/LDHB ratio (p<0.01 were significantly decreased. Endurance training had no effect on LDHA and LDH4. Conclusion: Endurance training is associated with oxidative shift of lactate dehydrogenase isoforms and isozymes in cerebrospinal fluid which could be considered as a prelude to aerobic metabolism of lactate in the brain.

  5. An update on the use of cerebrospinal fluid analysis as a diagnostic tool in multiple sclerosis.

    Science.gov (United States)

    Gastaldi, Matteo; Zardini, Elisabetta; Franciotta, Diego

    2017-01-01

    Intrathecal B-lymphocyte activation is a hallmark of multiple sclerosis (MS), a multi-factorial inflammatory-demyelinating disease of the central nervous system. Such activation has a counterpart in the cerebrospinal fluid (CSF) oligoclonal IgG bands (OCB), whose diagnostic role in MS has been downgraded within the current McDonald's criteria. With a theoretico-practical approach, the authors review the physiopathological basis of the CSF dynamics, and the state-of-the-art of routine CSF analysis and CSF biomarkers in MS. Areas covered: The authors discuss pros and cons of CSF analysis, including critical evaluations of both well-established, and promising diagnostic and prognostic laboratory tools. New acquisitions on the CSF and cerebral interstitial fluid dynamics are also presented. The authors searched the PubMed database for English-language articles reported between January 2010 and June 2016, using the key words 'multiple sclerosis', 'cerebrospinal fluid', 'oligoclonal bands'. Reference lists of relevant articles were scanned for additional studies. Expert commentary: The availability of performing high-quality, routine CSF tests in specialized laboratories, the emerging potential of novel CSF biomarkers, and the trend for early treatments should induce a reappraisal of CSF analysis for diagnostic and prognostic purposes in MS. Further procedural and methodological improvements seem to be necessary in both research and translational diagnostic CSF settings.

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

    Directory of Open Access Journals (Sweden)

    Michael G. Harrington

    2006-01-01

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

  7. [Simultaneous diagnosis of pseudomeningocele, tethered cord syndrome and cerebrospinal fluid fistula: Report of a case].

    Science.gov (United States)

    Quillo-Olvera, Javier; Zambrano-Velarde, Luis E; Velázquez-Santana, Héctor; Gutiérrez-Partida, Carlos F; Velázquez-García, Francisco; Alcántara-Gómez, Leopoldo A

    2016-01-01

    The clinical case is presented on a patient with an extensive sacral dysraphism, a history of myelomeningocele surgical repair in her childhood, as well as tethered cord syndrome. The patient was also diagnosed with pseudomeningocele and a cerebrospinal fluid cutaneous fístula. A surgical approach was used, with encouraging results being obtained in the clinical outcome of the patient. A review of the literature was performed to support the surgical decision in this case. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  8. Intramedullary papillary ependymoma with choroid plexus differentiation and cerebrospinal fluid dissemination to the brain.

    Science.gov (United States)

    Dulai, Mohanpal S; Caccamo, Dario V; Briley, Anita L; Edwards, Michael S B; Fisher, Paul G; Lehman, Norman L

    2010-05-01

    This 8-year-old girl presented with a papillary ependymoma in the thoracic spinal cord. Resection was followed by recurrence at the primary site and later in the lumbosacral thecal sac, followed by cerebrospinal fluid dissemination to the brain approximately 5 years after her initial presentation. The tumor showed cytological and immunohistochemical features overlapping those of classic ependymomas and choroid plexus tumors similar to those seen in uncommon supratentorial papillary ependymomas, also known as papillary tumors of the pineal region. The histopathological and clinical courses of this rare spinal papillary ependymoma exhibiting mixed ependymal and choroid plexus-like differentiation are discussed.

  9. Multiple sclerosis showing elevation of adenosine deaminase levels in the cerebrospinal fluid.

    Science.gov (United States)

    Samuraki, Miharu; Sakai, Kenji; Odake, Yasuko; Yoshita, Mitsuhiro; Misaki, Kouichi; Nakada, Mitsutoshi; Yamada, Masahito

    2017-04-01

    An 80-year-old man developed dysarthria, quadriplegia, sensory disturbance and ataxia in all limbs. Brain and spinal magnetic resonance imaging (MRI) revealed multiple enhanced lesions. Cerebrospinal fluid (CSF) levels of adenosine deaminase (ADA) remarkably elevated. Tuberculosis DNA was not detected, and tuberculosis was not cultured either in the CSF. Brain biopsy revealed the inflammatory demyelinating lesions. With the diagnosis of multiple sclerosis, corticosteroid therapy resulted in rapid improvement of his symptoms and MRI abnormalities. CSF levels of ADA also decreased. Multiple sclerosis should be included in differential diagnosis of disorders with ADA elevation in the CSF. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer’s Disease Brain

    OpenAIRE

    Rueli, Rachel H.L.H.; Parubrub, Arlene C.; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane H.; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

    2015-01-01

    Subjects with Alzheimer’s disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in compar...

  11. Algorithms for automated determination of cerebrospinal fluid volume in CT images

    International Nuclear Information System (INIS)

    Klotz, E.; Petersen, D.; Kindermann, U.; Kalender, W.A.

    1988-01-01

    The authors present algorithms for a reproducible and automatic determination of cerebrospinal fluid (CSF) volume from CT images. The brain is first isolated by determining the inner skull contour with a fast contour-tracking algorithm. By shrinking this contour, radial segments are defined that allow a description of CT value variation used to correct for field inhomogeneity. The CSF volume is found by using adaptive thresholding (fitting the radial segments) and/or region growing. Intra- and extraventricular CSF volumes can be evaluated separately by using either radial segments or an approximate interactive delineation. Results of a prospective patient study of the effect of alcohol withdrawal on CSF volume are presented

  12. Persistent dural cerebrospinal fluid leak shown by retrograde radionuclide myelography: case report

    International Nuclear Information System (INIS)

    Kadrie, H.; Driedger, A.A.; McInnis, W.

    1976-01-01

    Following inadvertent spinal anesthesia for delivery, a patient developed incapacitating post-lumbar puncture headache that persisted for 9 weeks. Scintigrams of the lumbar region, obtained after injection of /sup 99m/Tc-human serum albumin into the cisterna magna, showed the cerebrospinal fluid leak. Blood patch repair was carried out, with immediate relief of all symptoms. Because of subsequent atypical headaches, a second cisternogram was done by the same technique. This study confirmed that there was no further dural leak, and other evidence indicated that the recurrent headache was related to functional problems

  13. Cronobacter sakazakii DNA Detection in Cerebrospinal Fluid of a Patient with Amyotrophic Lateral Sclerosis Mimic Syndrome

    Directory of Open Access Journals (Sweden)

    Marianna Piombo

    2015-12-01

    Full Text Available A 45-year-old male noticed progressive weakness of the right lower limb with gait disturbance. Over the following months, motor deficits worsened, spreading to the right upper limb. Electromyography showed active denervation in the upper and lower limb muscles. A diagnosis of amyotrophic lateral sclerosis (ALS was made. About 2 years after symptom onset, gradual improvement occurred. Cerebrospinal fluid analysis performed about 3 years after the beginning of symptoms identified Cronobacter sakazakii. Since no other possible causes were identified, we suggest that an almost completely reversible ALS-like syndrome had been triggered by Cronobacter infection in our immunocompetent patient.

  14. Non Invasive Microwave Sensor for the Detection of Lactic Acid in Cerebrospinal Fluid (CSF)

    International Nuclear Information System (INIS)

    Goh, J H; Mason, A; Al-Shamma'a, A I; Field, M; Shackcloth, M; Browning, P

    2011-01-01

    This research involves the use of a low power microwave sensor for analysis of lactic acid in cerebrospinal fluid (CSF), an indicator of neurological impairment during aortic aneurysm surgery which could provide the basis for improved treatment regimes and better quality of care with more efficient use of resources. This paper presents initial work using standard lactate curves in water followed by lactate in s ynthetic CSF . A multi-modal spectral signature has been defined for lactate, forming the basis for subsequent development of microwave sensor platform that is able to detect concentrations of lactic acid in CSF of volumes less than 1ml.

  15. Cerebrospinal fluid otorrhea and recurrent bacterial meningitis in a pediatric case with Mondini dysplasia.

    Science.gov (United States)

    Işeri, Mete; Uçar, Selçuk; Derin, Serhan; Ustündağ, Emre

    2013-01-01

    Mondini dysplasia is a congenital malformation of the inner ear, which is characterized by a short and large cochlear canal of 1.5 turn rather than 2.5 turns and an apical region with cystic dilatation. Patients present with congenital deafness, when both cochlea are affected. Unilateral disease may cause recurrent meningitis, otorrhea or rhinorrhea. In this article, we report a three-year-old pediatric case with a history of meningitis and cerebrospinal fluid otorrhea following tympanostomy tube placement for serous otitis media.

  16. Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt–Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years

    Science.gov (United States)

    Sanchez-Juan, Pascual; Gawinecka, Joanna; Green, Alison; Ladogana, Anna; Pocchiari, Maurizio; Sanchez-Valle, Raquel; Mitrova, Eva; Sklaviadis, Theodor; Kulczycki, Jerzy; Slivarichova, Dana; Saiz, Albert; Calero, Miguel; Knight, Richard; Aguzzi, Adriano; Laplanche, Jean-Louis; Peoc’h, Katell; Schelzke, Gabi; Karch, Andre; van Duijn, Cornelia M.; Zerr, Inga

    2012-01-01

    To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt–Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions. Within the framework of a European Community supported longitudinal multicentre study (‘cerebrospinal fluid markers’) we analysed the spectrum of rapid progressive dementia diagnoses, their potential influence on 14-3-3 specificity as well as results of other dementia markers (tau, phosphorylated tau and amyloid-β1–42) and evaluated the specificity of 14-3-3 in Creutzfeldt–Jakob disease diagnosis for the years 1998–2008. A total of 29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other cerebrospinal fluid dementia markers in patients with rapid dementia and suspected Creutzfeldt–Jakob disease in the participating centres. In 10 731 patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was analysed for Creutzfeldt–Jakob disease with respect to increasing cerebrospinal fluid tests per year and spectrum of differential diagnosis. Ring trials were performed to ensure the comparability between centres during the reported time period. Protein 14-3-3 test specificity remained high and stable in the diagnosis of Creutzfeldt–Jakob disease during the observed time period across centres (total specificity 92%; when compared with patients with definite diagnoses only: specificity 90%). However, test specificity varied with respect to differential diagnosis. A high 14-3-3 specificity was obtained in differentiation to other neurodegenerative diseases (95–97%) and non

  17. Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years.

    Science.gov (United States)

    Stoeck, Katharina; Sanchez-Juan, Pascual; Gawinecka, Joanna; Green, Alison; Ladogana, Anna; Pocchiari, Maurizio; Sanchez-Valle, Raquel; Mitrova, Eva; Sklaviadis, Theodor; Kulczycki, Jerzy; Slivarichova, Dana; Saiz, Albert; Calero, Miguel; Knight, Richard; Aguzzi, Adriano; Laplanche, Jean-Louis; Peoc'h, Katell; Schelzke, Gabi; Karch, Andre; van Duijn, Cornelia M; Zerr, Inga

    2012-10-01

    To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt-Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions. Within the framework of a European Community supported longitudinal multicentre study ('cerebrospinal fluid markers') we analysed the spectrum of rapid progressive dementia diagnoses, their potential influence on 14-3-3 specificity as well as results of other dementia markers (tau, phosphorylated tau and amyloid-β(1-42)) and evaluated the specificity of 14-3-3 in Creutzfeldt-Jakob disease diagnosis for the years 1998-2008. A total of 29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other cerebrospinal fluid dementia markers in patients with rapid dementia and suspected Creutzfeldt-Jakob disease in the participating centres. In 10 731 patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was analysed for Creutzfeldt-Jakob disease with respect to increasing cerebrospinal fluid tests per year and spectrum of differential diagnosis. Ring trials were performed to ensure the comparability between centres during the reported time period. Protein 14-3-3 test specificity remained high and stable in the diagnosis of Creutzfeldt-Jakob disease during the observed time period across centres (total specificity 92%; when compared with patients with definite diagnoses only: specificity 90%). However, test specificity varied with respect to differential diagnosis. A high 14-3-3 specificity was obtained in differentiation to other neurodegenerative diseases (95-97%) and non

  18. Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

    Directory of Open Access Journals (Sweden)

    Letícia Aparecida Schiave

    2018-01-01

    Full Text Available Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400–800 mg.

  19. Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels.

    Science.gov (United States)

    Sariego-Jamardo, Andrea; García-Cazorla, Angels; Artuch, Rafael; Castejón, Esperanza; García-Arenas, Dolores; Molero-Luis, Marta; Ormazábal, Aida; Sanmartí, Francesc Xavier

    2015-11-01

    The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Philipp Spitzer

    2011-01-01

    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.

  1. Clinical and cerebrospinal fluid findings contribute to the early differentiation between infectious and noninfectious encephalitis

    Directory of Open Access Journals (Sweden)

    Miguel Wilken

    2017-06-01

    Full Text Available Early recognition and prompt specific treatment are crucial factors influencing the outcome of patients with acute encephalitis. The aim of this study was to determine the main causes of acute encephalitis in our population and to find predictors that may lead to specific diagnosis. Adult patients admitted to our hospital with suspected diagnosis of encephalitis in the period 2006-2013 were included. One hundred and five medical records were analyzed. Eighty-two patients with infectious encephalitis were identified (78% of total cases, 53 (65% men and 29 (35% women, mean age 47.8 years. The most common microorganisms identified were: HSV-1 (11%, VZV (10%, HSV-2 (5% and EBV (5%. Twenty-three patients (22% of the series had non-infectious encephalitis. Headache (p < 0.0001 and fever (p = 0.008 were more frequent in encephalitis of infectious origin. Protein levels and white blood cell counts in the cerebrospinal fluid were significantly higher in patients affected by infectious encephalitis than in those affected by noninfectious encephalitis (OR 95% CI 12.3 [2.9-51.7] and OR 95% CI 7.4 [2-27], respectively. Identifying specific causal agents of acute encephalitis remains a major challenge. Cerebrospinal fluid markers, as well as specific clinical findings, may however contribute to initial differentiation between infectious and noninfectious causes.

  2. Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Gmitterová, K; Heinemann, U; Krasnianski, A; Gawinecka, J; Zerr, I

    2016-06-01

    Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P disease duration and clinical stage influenced the test sensitivity in all proteins. Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known. © 2016 EAN.

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

    Science.gov (United States)

    Spitzer, Philipp; Schieb, Heinke; Kamrowski-Kruck, Heike; Otto, Markus; Chiasserini, Davide; Parnetti, Lucilla; Herukka, Sanna-Kaisa; Schuchhardt, Johannes; Wiltfang, Jens; Klafki, Hans-Wolfgang

    2011-01-01

    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. PMID:22145083

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

    Directory of Open Access Journals (Sweden)

    Murad Baba

    2016-01-01

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

  5. Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

    Science.gov (United States)

    Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

    2017-06-01

    Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

  6. [Changes in cerebrospinal fluid in patients with tuberculosis of the central nervous system].

    Science.gov (United States)

    Jedrychowski, Michał; Garlicki, Aleksander

    2008-01-01

    The aim of the study was to analyze the parameters of the cerebrospinal fluid in patients with tuberculosis of the central nervous system confirmed by culture or molecular methods, in comparison to patients without such confirmation. The analysis of medical documentation of 13 patients with CNS tuberculosis, 10 male and 3 female who were hospitalized at the Clinic of Infectious Diseases in Kraków in years 2001-2006 was performed. Following parameters of the cerebrospinal fluid were taken into account in both groups of patients: cytologic analysis, protein, glucose and chloride concentration. Statistical analysis was done using the non-parametric Mann-Whitney U test. The only parameter for which statistically significant difference between the two groups of patients was found was the level of glucose in CSF (p<0.05). Lower glucose concentration was observed in the group with etiologically confirmed CNS tuberculosis. Moreover additional localisation of tuberculosis was observed in this group of patients. Introduction of the molecular biology methods in diagnosis allowed to detect the etiologic factor more often.

  7. Vaginal Migration of Ventriculoperitoneal Shunt Catheter and Cerebrospinal Fluid Leak as a Complication of Hysterectomy.

    Science.gov (United States)

    Houten, John K; Smith, Shiela; Schwartz, Amit Y

    2017-08-01

    Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure to treat hydrocephalus that diverts cerebrospinal fluid from the cerebral ventricles to the peritoneal cavity for reabsorption. The distal catheter may potentially migrate through any potential or iatrogenic opening in the peritoneal cavity. Increasingly successfully management of childhood hydrocephalus and adult-onset conditions leading to hydrocephalus, such as subarachnoid hemorrhage, is leading many adult female patients harboring VP shunts needing to undergo hysterectomy. Hysterectomy creates a potential defect though which a VP shunt catheter may migrate. It is not known whether the hysterectomy cuff closure technique may affect the likelihood of distal catheter migration though the repair site. We report the case of a 38-year-old woman with a VP shunt who underwent laparoscopic hysterectomy via an open vaginal cuff technique who subsequently presented with vaginal cerebrospinal fluid leakage secondary to migration of the distal shunt catheter through the hysterectomy cuff. Vaginal migration of the distal VP shunt catheter is a possible complication of hysterectomy. The authors postulate that an open cuff hysterectomy closure technique may increase the risk of catheter migration, an issue that may be better understood with further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Blood-Cerebrospinal Fluid Barrier Permeability in Alzheimer’s Disease1

    Science.gov (United States)

    Chalbot, Sonia; Zetterberg, Henrik; Blennow, Kaj; Fladby, Tormod; Andreasen, Niels; Grundke-Iqbal, Inge; Iqbal, Khalid

    2011-01-01

    The role of blood-cerebrospinal fluid barrier (BCB) dysfunction in Alzheimer’s disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinal fluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-β1–42 (Aβ1–42), and ubiquitin CSF levels. We found that due to its higher sensitivity, CSF sPLA2 activity could 1) discriminate AD from healthy controls and 2) showed BCB impairment in neurological control cases while QAlb could not. Moreover, the CSF sPLA2 activity measurement showed that around half of the AD patients were characterized by a BCB impairment. The BCB dysfunction observed in AD was independent from Mini-Mental State Examination score as well as CSF levels of total tau, Aβ1–42, and ubiquitin. Finally, the BCB dysfunction was not limited to any of the CSF biomarkers-based previously identified subgroups of AD. These results suggest that the BCB damage occurs independent of and probably precedes both Aβ and tau pathologies in a restricted subgroup of AD patients. PMID:21471645

  9. LEVELS OF NEUROSPECIFIC MARKERS IN CEREBROSPINAL FLUID OF ADULT PATIENTS WITH BACTERIAL MENINGITIS.

    Science.gov (United States)

    Sokhan, A; Zots, Y; Gavrylov, A; Iurko, K; Solomennik, A; Kuznietsova, A

    2017-09-01

    At present, the great attention is given to the neurospecific markers as their elevated level in the cerebrospinal fluid corresponds to the degree of destruction of relevant CNS cells. Therefore, actual direction of the studies of the pathogenesis and diagnosis of CNS diseases is to determine levels of neurospecific markers in the cerebrospinal fluid (CSF). The purpose of the study was to evaluate the diagnostic and prognostic role of NSE, S-100 protein, GFAP and MBP levels in CSF of patients with acute bacterial meningitis. S-100 protein, NSE, GFAP and MBP levels in CSF of patients with acute pneumococcal and meningococcal meningitis were determined during admission and after 10-12 days of treatment. Patients were divided into groups depending on the etiology and severity of the disease. 60 cases of acute bacterial meningitis, as a study group, and 12 cases with acute respiratory infection and meningism, as a control group, were analyzed. It is shown that CSF levels of NSE, S-100 protein, GFAP and MBP on the first day of admission were significantly increased (P<0,05), depending on the severity of the disease. The highest levels of neurospecific markers have been identified in non-survivors (P<0,001). The concentration changes of CSF neurospecific markers are found to be helpful as a diagnostic and prognostic marker in acute bacterial meningitis.

  10. Cerebrospinal fluid cytotoxicity does not affect survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Galán, L; Matías-Guiu, J; Matias-Guiu, J A; Yáñez, M; Pytel, V; Guerrero-Sola, A; Vela-Souto, A; Arranz-Tagarro, J A; Gómez-Pinedo, U; García, A G

    2017-09-01

    Cerebrospinal fluid (CSF) from some patients with amyotrophic lateral sclerosis (ALS) has been demonstrated to significantly reduce the neuronal viability of primary cell cultures of motor neurons. We aimed to study the potential clinical consequences associated with the cytotoxicity of CSF in a cohort of patients with ALS. We collected CSF from thirty-one patients with ALS. We analysed cytotoxicity by incubating it into the primary cultures of motor cortex neurons. Neural viability was quantified after 24 hours using the colorimetric MTT reduction assay. All patients were followed up from the moment of diagnosis to death, and a complete evaluation during disease progression and survival was performed, including gastrostomy and respiratory assistance. Twenty-one patients (67.7%) presented a cytotoxic CSF. There were no significant differences between patients with and without cytotoxicity regarding mean time from symptom onset to the diagnosis, from the diagnosis to death, from the diagnosis to respiratory assistance with BIPAP, from diagnosis to gastrostomy and from the onset of symptoms to death. In Cox regression analysis, bulbar onset, but not cytotoxicity, gender or age at onset, was associated with a lower risk of survival. Cerebrospinal fluid cytotoxicity was not associated with differential survival rates. This suggests that the presence of cytotoxicity in CSF, measured through neuronal viability in primary cultures of motor cortex neurons, could reflect different mechanisms of the disease, but it does not predict disease outcome. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Relationship of Human Immunodeficiency Virus Viral Load in Cerebrospinal Fluid and Plasma in Patients Co-infected With Cryptococcal Meningitis.

    Science.gov (United States)

    Chang, Christina C; Kangethe, Richard; Omarjee, Saleha; Hiramen, Keshni; Gosnell, Bernadett; Sojane, Katlego; Moosa, Mohamed-Yunus S; Lewin, Sharon R; French, Martyn A; Ndung'u, Thumbi

    2017-01-01

    We measured human immunodeficiency virus (HIV) ribonucleic acid (RNA) in paired cerebrospinal fluid (CSF) and plasma samples in a prospective study of 91 HIV-infected, antiretroviral therapy-naive patients with cryptococcal meningitis. Cerebrospinal fluid HIV RNA was lower than in plasma (median 4.7 vs 5.2 log 10 copies/mL, P < .0001) and positively correlated with plasma HIV RNA, peripheral CD4 + T-cell percentage, and CSF CXCL10. Plasma/CSF ratio of HIV RNA ranged widely from 0.2 to 265.5 with a median of 2.6. Cerebrospinal fluid quantitative cryptococcal culture positively correlated with CSF CCL2 and CCL3. CSF-plasma viral discordance was not associated with cryptococcal-associated immune reconstitution inflammatory syndrome.

  12. Peri-operative cerebrospinal fluid leak during single-stage bone-anchored hearing aid implantation: case report.

    Science.gov (United States)

    Dimbleby, G; Mitchell-Innes, A; Murphy, J

    2014-12-01

    A bone-anchored hearing aid uses the principle of bone conduction and osseointegration to transfer sound vibrations to a functioning inner ear. It consists of a permanent titanium implant, and removable abutment and sound processor. Informed consent requires discussion of the procedural benefits, alternatives and complications. The risks of bone-anchored hearing aid surgery include infection, soft tissue hypertrophy, skin graft or flap failure, osseointegration failure, and the need for further surgery. A case of cerebrospinal fluid leak in a patient undergoing bone-anchored hearing aid surgery is reported and discussed. Bone-anchored hearing aid surgery poses a risk of breaching the inner table of the temporal bone and dura, resulting in a cerebrospinal fluid leak; the risk of meningitis is rare but serious. The surgeon should discuss the possibility of cerebrospinal fluid leak when consenting patients. Pre-operative computerised tomography scanning should be considered in certain individuals to aid implant placement.

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

    Directory of Open Access Journals (Sweden)

    Domenico Ventrella

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

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

    Science.gov (United States)

    Ventrella, Domenico; Laghi, Luca; Barone, Francesca; Elmi, Alberto; Romagnoli, Noemi; Bacci, Maria Laura

    2016-01-01

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

  15. Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.

    Science.gov (United States)

    Lautner, Ronald; Palmqvist, Sebastian; Mattsson, Niklas; Andreasson, Ulf; Wallin, Anders; Pålsson, Erik; Jakobsson, Joel; Herukka, Sanna-Kaisa; Owenius, Rikard; Olsson, Bob; Hampel, Harald; Rujescu, Dan; Ewers, Michael; Landén, Mikael; Minthon, Lennart; Blennow, Kaj; Zetterberg, Henrik; Hansson, Oskar

    2014-10-01

    Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown. To evaluate whether the APOE genotype affects the diagnostic accuracy of CSF biomarkers for Alzheimer disease (AD), in particular Aβ42 levels, and whether the association of APOE ε4 with CSF biomarkers depends on cortical Aβ status. We collected data from 4 different centers in Sweden, Finland, and Germany. Cohort A consisted of 1345 individuals aged 23 to 99 years with baseline CSF samples, including 309 with AD, 287 with prodromal AD, 399 with stable mild cognitive impairment, 99 with dementias other than AD, and 251 controls. Cohort B included 105 nondemented younger individuals (aged 20-34 years) with CSF samples available. Cohort C included 118 patients aged 60 to 80 years with mild cognitive symptoms who underwent flutemetamol F 18 ([18F]flumetamol) positron emission tomography amyloid imaging and CSF tap. Standard care. Cerebrospinal fluid levels of Aβ42 and total and phosphorylated tau in relation to the APOE ε2/ε3/ε4 polymorphism in different diagnostic groups and in cases with or without cortical uptake of [18F]flutemetamol. The CSF levels of Aβ42 but not total and phosphorylated tau were lower in APOE ε4 carriers compared with noncarriers irrespective of diagnostic group (cohort A). Despite this, CSF levels of Aβ42 differed between participants with AD when compared with controls and those with stable mild cognitive impairment, even when stratifying for APOE genotype (P Alzheimer's Disease Neuroimaging Initiative (ADNI) using carbon 11-labeled Pittsburgh Compound B scanning. Cerebrospinal fluid levels of Aβ42 are strongly associated with the diagnosis of AD and cortical Aβ accumulation independent

  16. Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment.

    Science.gov (United States)

    Zetterberg, Henrik; Jakobsson, Joel; Redsäter, Mikael; Andreasson, Ulf; Pålsson, Erik; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette Gm; Blennow, Kaj; Landén, Mikael

    2014-07-30

    Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Alfred N Fonteh

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

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

    Directory of Open Access Journals (Sweden)

    WANG Wei-zhi

    2013-02-01

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

  19. Effects of irradiation and probenecid on cerebrospinal fluid transport of penicillin

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    Kourtopoulos, H.; Holm, S.E.; Norrby, S.R. (Umeaa Univ. (Sweden))

    1983-03-01

    A hitherto unrecognized interaction between whole brain irradiation and probenecid on cerebrospinal fluid (CSF) transport of benzylpenicillin has been demonstrated in rabbits. Healthy adult rabbits received 10 Gy (1000 rad) to the whole brain as a single dose. At different time intervals after irradiation the animals were subjected to single intravenous injections of benzylpenicillin. Studies on benzylpenicillin concentrations in CSF showed increasing values one week after irradiation suggesting a disturbance in blood-CSF barriers. Additionally, groups of rabbits were subjected to either irradiation, probenecid injections or both prior to antibiotic administration. All these treatments resulted in increased CSF concentration of benzylpenicillin relative to the concurrent serum levels. The increase of the CSF benzylpenicillin levels in the preirradiated animals was less pronounced in the animals treated with probenecid, compared to those who were irradiated only.

  20. Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Relation of Odor Identification with Alzheimer's Disease Markers in Cerebrospinal Fluid and Cognition

    DEFF Research Database (Denmark)

    Reijs, Babette L R; Ramakers, Inez H G B; Elias-Sonnenschein, Lyzel

    2017-01-01

    BACKGROUND: Impaired olfactory function is an early characteristic of Alzheimer's disease (AD), but it remains unclear if odor identification also relates to early markers of AD in cerebrospinal fluid (CSF). OBJECTIVE: To investigate the association between odor identification and amyloid-β 1...... individuals (40 with normal cognition, 45 with mild cognitive impairment (MCI), 42 with AD-type dementia, and 26 individuals with non-AD dementia) from the EDAR study. Individuals were recruited from six memory clinics across Europe. Odor identification was tested with the brief University of Pennsylvania...... Smell Identification Test. CSF Aβ42 and t-tau were assessed with INNO-BIA AlzBio3 Luminex assay. Neuropsychological assessment included tests for verbal memory, verbal fluency, attention, executive function, and visuoconstruction. Follow-up was performed within 3 years after baseline. RESULTS: Lower...

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

    DEFF Research Database (Denmark)

    Møllgaard, M; Degn, M; Sellebjerg, F

    2016-01-01

    ) 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. Our......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......, 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...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    concentration was blood contaminated samples centrifuged at 2000 × g. When a protease inhibitor cocktail was added to the CSF prior to centrifugation, the DJ-1 concentration was significantly higher. CONCLUSION: Preanalytical factors such as centrifugation and protease inhibition must...... be carefully controlled when handling CSF for analysis of DJ-1 and other biomarkers, as DJ-1 was influenced by blood contamination, centrifugation and protease activity.......AIM: The purpose of this study was to establish the influence of centrifugation and protease activity on the cerebrospinal fluid (CSF) concentrations of DJ-1 and hemoglobin. MATERIALS & METHODS: The concentrations of DJ-1 and hemoglobin were determined in 12 (DJ-1) and six (hemoglobin) pairs of CSF...

  4. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells

    Science.gov (United States)

    Lehtinen, Maria K.; Zappaterra, Mauro W.; Chen, Xi; Yang, Yawei J.; Hill, Anthony; Lun, Melody; Maynard, Thomas; Gonzalez, Dilenny; Kim, Seonhee; Ye, Ping; D’Ercole, A. Joseph; Wong, Eric T.; LaMantia, Anthony S.; Walsh, Christopher A.

    2011-01-01

    Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions. PMID:21382550

  5. Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat

    International Nuclear Information System (INIS)

    Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J.

    1990-01-01

    Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function

  6. Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome.

    Science.gov (United States)

    Denning, D W; Armstrong, R W; Lewis, B H; Stevens, D A

    1991-09-01

    Increased intracranial pressure has been a noteworthy problem in some of our patients with cryptococcal meningitis and acquired immunodeficiency syndrome (AIDS), and this appears to be a feature observed in patients with cryptococcal meningitis reported in the literature. Whereas most attention of clinicians is presently focused on optimizing the antifungal regimen, so as to improve on high failure rates in cryptococcal meningitis in AIDS, little attention has been paid to the problem of intracranial hypertension. We argue that visual loss and some of the cases of death early after the onset of chemotherapy may be related to high cerebrospinal fluid (CSF) pressure, regardless of antifungal therapy. The possible pathophysiologic mechanisms are discussed, and we postulate that the mechanism is reduced CSF outflow possibly due to increased outflow resistance, not necessarily accompanied by prominent cerebral edema. Optimal therapy of this complication is not yet established, but some measures that may be helpful are ventricular shunting, frequent high-volume lumbar punctures, and possibly glucocorticoids.

  7. Cerebrospinal fluid can be used for HIV genotyping when it fails in blood

    Science.gov (United States)

    Rotta, Indianara; Raboni, Sonia Mara; Ribeiro, Cléa Elisa Lopes; Riedel, Maristela; Winhescki, Maria da Graça; Smith, Davey M.; Ellis, Ronald J.; de Almeida, Sérgio Monteiro

    2014-01-01

    Blood plasma specimens are the clinical standard for HIV-1 pol gene genotyping from viral populations; however, it is not always successful, often from low viral loads or the presence of polymerase chain reaction (PCR) inhibitors. Objective To describe the successful of HIV-1 genotyping in two samples of cerebrospinal fluid (CSF), after genotype procedures failed from blood. Method Two HIV-infected patients enrolled in a neurocognitive research study were evaluated when standard HIV-1 genotyping failed from blood plasma samples. Genotyping was performed using the commercial system TRUGENE® HIV-1 Genotyping Kit and the OpenGene® DNA Sequencing System (Siemens Healthcare Diagnostics, Tarrytown, NY, USA). Results CSF genotyping was performed via the same commercial platform and was successful in both cases. Conclusion This report demonstrates that CSF could be used as an alternate clinical specimen for HIV-1 genotyping when it fails from blood. PMID:25054982

  8. Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.

    Directory of Open Access Journals (Sweden)

    Joanna M Lubieniecka

    Full Text Available One of the major challenges in management of spinal cord injury (SCI is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS analyses of cerebrospinal fluid (CSF collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.

  9. Slc20a2 is critical for maintaining a physiologic inorganic phosphate level in cerebrospinal fluid.

    Science.gov (United States)

    Jensen, Nina; Autzen, Jacob Kwasi; Pedersen, Lene

    2016-04-01

    Mutations in the SLC20A2-gene encoding the inorganic phosphate (Pi) transporter PiT2 can explain approximately 40% of the familial cases of the rare neurodegenerative disorder primary familial brain calcification (Fahr's disease). The disease characteristic, cerebrovascular-associated calcifications, is also present in Slc20a2-knockout (KO) mice. Little is known about the specific role(s) of PiT2 in the brain. Recent in vitro studies, however, suggest a role in regulation of the [Pi] in cerebrospinal fluid (CSF). We here show that Slc20a2-KO mice indeed have a high CSF [Pi] in agreement with a role of PiT2 in Pi export from the CSF. The implications in relation to disease mechanism are discussed.

  10. Demonstration that a new flow sensor can operate in the clinical range for cerebrospinal fluid flow.

    Science.gov (United States)

    Raj, Rahul; Lakshmanan, Shanmugamurthy; Apigo, David; Kanwal, Alokik; Liu, Sheng; Russell, Thomas; Madsen, Joseph R; Thomas, Gordon A; Farrow, Reginald C

    2015-10-01

    A flow sensor has been fabricated and tested that is capable of measuring the slow flow characteristic of the cerebrospinal fluid in the range from less than 4 mL/h to above 100 mL/h. This sensor is suitable for long-term implantation because it uses a wireless external spectrometer to measure passive subcutaneous components. The sensors are pressure-sensitive capacitors, in the range of 5 pF with an air gap at atmospheric pressure. Each capacitor is in series with an inductor to provide a resonant frequency that varies with flow rate. At constant flow, the system is steady with drift capacitor system is proposed that can measure flow, which is fully compensated for all hydrostatic pressures. For twin capacitors, other sources of systematic variation within clinical range, such as temperature and ambient pressure, are smaller than our sensitivity and we delineate a calibration method that should maintain clinically useful accuracy over long times.

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

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    Paolo Colomba

    2014-12-01

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

  12. Preference for novel faces in male infant monkeys predicts cerebrospinal fluid oxytocin concentrations later in life.

    Science.gov (United States)

    Madrid, Jesus E; Oztan, Ozge; Sclafani, Valentina; Del Rosso, Laura A; Calonder, Laura A; Chun, Katie; Capitanio, John P; Garner, Joseph P; Parker, Karen J

    2017-10-11

    The ability to recognize individuals is a critical skill acquired early in life for group living species. In primates, individual recognition occurs predominantly through face discrimination. Despite the essential adaptive value of this ability, robust individual differences in conspecific face recognition exist, yet its associated biology remains unknown. Although pharmacological administration of oxytocin has implicated this neuropeptide in face perception and social memory, no prior research has tested the relationship between individual differences in face recognition and endogenous oxytocin concentrations. Here we show in a male rhesus monkey cohort (N = 60) that infant performance in a task used to determine face recognition ability (specifically, the ability of animals to show a preference for a novel face) robustly predicts cerebrospinal fluid, but not blood, oxytocin concentrations up to five years after behavioural assessment. These results argue that central oxytocin biology may be related to individual face perceptual abilities necessary for group living, and that these differences are stable traits.

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

    DEFF Research Database (Denmark)

    Modvig, Signe; Degn, M; Sander, B

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Ostergaard, Christian; Benfield, Thomas

    2009-01-01

    .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 (5961-22725......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......) levels of MIF in 171 patients clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis with a known aetiology, 20 to have purulent meningitis with an unknown aetiology, 59 to have lymphocytic meningitis, and 11 to have encephalitis, whereas 50 were...

  15. Cerebrospinal fluid can be used for HIV genotyping when it fails in blood

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    Indianara Rotta

    2014-07-01

    Full Text Available Blood plasma specimens are the clinical standard for HIV-1 pol gene genotyping from viral populations; however, it is not always successful, often from low viral loads or the presence of polymerase chain reaction (PCR inhibitors. Objective To describe the successful of HIV-1 genotyping in two samples of cerebrospinal fluid (CSF, after genotype procedures failed from blood. Method Two HIV-infected patients enrolled in a neurocognitive research study were evaluated when standard HIV-1 genotyping failed from blood plasma samples. Genotyping was performed using the commercial system TRUGENE® HIV-1 Genotyping Kit and the OpenGene® DNA Sequencing System (Siemens Healthcare Diagnostics, Tarrytown, NY, USA. Results CSF genotyping was performed via the same commercial platform and was successful in both cases. Conclusion This report demonstrates that CSF could be used as an alternate clinical specimen for HIV-1 genotyping when it fails from blood.

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

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    Sergio Monteiro de Almeida

    2013-09-01

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

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

    Science.gov (United States)

    Almeida, Sérgio Monteiro de

    2013-09-01

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

  18. Neuromyelitis optica IgG in the cerebrospinal fluid induces astrocytopathy in optic nerve

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Lillevang, Søren Thue; Mørch, Marlene

    was coincident with deposition of complement. Histopathological lesions were markedly enhanced with extensive/long-segment astrocytopathy of optic nerve and optic chiasm involvement in AQP4- IgG+ C + anti-CD59a treated mice. Such pathology was not seen in mice receiving normal human IgG, C and anti-CD59a......Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Optic neuritis (ON) is believed to be immune-mediated and is associated with AQP4-IgG in NMOSD......-ON. The predilection of the optic nerve in NMOSD may partly be explained by the dense expression of AQP4 in the optic nerve. We previously reported that AQP4-IgG in cerebrospinal fluid (CSF) becomes widely distributed in the brain and causes complementdependent astrocyte injury in periventricular areas and brain...

  19. Cerebrospinal fluid syndromes in HIV-positive patients with acute consciousness compromise

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    Batista Marcus Sabry Azar

    1999-01-01

    Full Text Available We reviewed the cerebrospinal fluid (CSF syndromes of 100 consecutive HIV-positive patients presenting acute consciousness compromise in emergency rooms, and correlated them with clinical data. The most frequent CSF syndromes were: absolute protein-cytological dissociation (21, viral (19, neurocryptococcosis (7, relative protein-cytological dissociation (6 and septic (4, moderate hypoglycorrachia (4, severe hypoglycorrachia (4 and hydroelectrolytic disturbance (3. One fifth of the patients had CSF syndromes considered sufficient for diagnosis or an immediate clinical decision. The most common clinical data were infective and neurological. There was little correlation between the clinical data and the CSF syndromes. We conclude that in HIV-positive individuals presenting acute consciousness disturbances there are frequently non-specific results in the CSF analysis that must be weighed against a detailed history and thorough physical examination. Taking this into account, in about one fifth of cases the CSF analysis can offer useful information for treatment.

  20. Interleukin 10 Level in the Cerebrospinal Fluid as a Possible Biomarker for Lymphomatosis Cerebri.

    Science.gov (United States)

    Hashiguchi, Shunta; Momoo, Takayuki; Murohashi, Yoko; Endo, Masanao; Shimamura, Megumi; Kawasaki, Takashi; Kanada, Sachie; Nozawa, Akinori; Tada, Mikiko; Koyano, Shigeru; Tanaka, Fumiaki

    2015-01-01

    A 71-year-old immunocompetent man developed cognitive decline and gait disturbance. Brain magnetic resonance imaging (MRI) revealed bilateral diffuse leukoencephalopathy without a mass lesion. An analysis of the cerebrospinal fluid (CSF) showed elevated levels of interleukin (IL)-10. The condition of the patient progressively deteriorated, and intravenous high-dose steroids proved ineffective. Detection of non-destructive, diffusely infiltrating, large B-cell lymphoma in biopsy and autopsy specimens led to a diagnosis of lymphomatosis cerebri (LC). On serial MRI, the basal ganglia and white matter lesions increased in parallel with the levels of IL-10. These findings suggest that the IL-10 level in the CSF may represent a potentially useful biomarker for the early diagnosis and monitoring of the disease progression in LC.

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

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    Jorge A. Benetucci

    2012-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-07-01

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

  3. Usefulness of interleukin 6 levels in the cerebrospinal fluid for the diagnosis of bacterial meningitis.

    Science.gov (United States)

    Takahashi, Waka; Nakada, Taka-aki; Abe, Ryuzo; Tanaka, Kumiko; Matsumura, Yosuke; Oda, Shigeto

    2014-08-01

    Interleukin 6 (IL-6) is a proinflammatory cytokine produced during infections. We hypothesized that IL-6 levels in the cerebrospinal fluid (CSF) would be elevated in bacterial meningitis and useful for diagnosing and predicting neurologic outcomes. For the differentiation of bacterial meningitis, serum and CSF samples were obtained from patients with an altered level of consciousness. Patients were classified into 3 groups: bacterial meningitis, nonbacterial central nervous system disease, and other site sepsis. Of the 70 patients included in this study, there were 13 in the bacterial meningitis group, 21 in the nonbacterial central nervous system disease group, and 36 in the other site sepsis group. The CSF IL-6 level was significantly higher in the bacterial meningitis group than in the other 2 groups (Pbacterial meningitis. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Serum and cerebrospinal fluid levels of transthyretin in Lewy body disorders with and without dementia.

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    Walter Maetzler

    Full Text Available Parkinson's disease (PD without (non-demented, PDND and with dementia (PDD, and dementia with Lewy bodies (DLB are subsumed under the umbrella term Lewy body disorders (LBD. The main component of the underlying pathologic substrate, i.e. Lewy bodies and Lewy neurites, is misfolded alpha-synuclein (Asyn, and--in particular in demented LBD patients--co-occurring misfolded amyloid-beta (Abeta. Lowered blood and cerebrospinal fluid (CSF levels of transthyretin (TTR--a clearance protein mainly produced in the liver and, autonomously, in the choroid plexus--are associated with Abeta accumulation in Alzheimer's disease. In addition, a recent study suggests that TTR is involved in Asyn clearance. We measured TTR protein levels in serum and cerebrospinal fluid of 131 LBD patients (77 PDND, 26 PDD, and 28 DLB and 72 controls, and compared TTR levels with demographic and clinical data as well as neurodegenerative markers in the CSF. Five single nucleotide polymorphisms of the TTR gene which are considered to influence the ability of the protein to carry its ligands were also analyzed. CSF TTR levels were significantly higher in LBD patients compared to controls. Post-hoc analysis demonstrated that this effect was driven by PDND patients. In addition, CSF TTR levels correlated negatively with CSF Abeta(1-42, total tau and phospho-tau levels. Serum TTR levels did not significantly differ among the studied groups. There were no relevant associations between TTR levels and genetic, demographic and clinical data, respectively. These results suggest an involvement of the clearance protein TTR in LBD pathophysiology, and should motivate to elucidate TTR-related mechanisms in LBD in more detail.

  5. Impaired cerebrospinal fluid dynamics along the entire optic nerve in normal-tension glaucoma.

    Science.gov (United States)

    Pircher, Achmed; Montali, Margherita; Wostyn, Peter; Pircher, Joachim; Berberat, Jatta; Remonda, Luca; Killer, Hanspeter E

    2018-03-12

    To investigate the cerebrospinal fluid (CSF) dynamics along the entire optic nerve (ON) in patients with normal-tension glaucoma (NTG). Retrospective analysis of computed tomographic (CT) cisternographies in Caucasian patients with NTG. Fifty-six patients (99 of 112 eyes) fulfilled the diagnostic criteria of NTG and underwent CT-cisternography. Twelve subjects without NTG (24 eyes) served as controls. Contrast-loaded cerebrospinal fluid (CLCSF) density measurements in Hounsfield units (HU) were performed at four defined regions along the ON and in the basal cistern. In NTG patients, the mean density CLCSF in the bulbar segment measured 76 ± 49 HU right and 88 ± 74 HU left, in the mid-orbital segment 117 ± 92 HU right and 119 ± 73 HU left, in the intracanalicular ON portion 209 ± 88 HU right and 216 ± 101 HU left, in the intracranial ON portion 290 ± 106 HU right and 286 ± 118 HU left and in the basal cistern 517 ± 213 HU. The distribution of CLCSF along the ON showed a statistically significant reduction in the intraorbital ON segments in NTG patients compared to controls without NTG with the far largest difference within the retrobulbar segment (-150 HU right and -117 HU left; right: p dynamics along the ON may contribute to the pathophysiology of NTG. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Evaluation of Spontaneous Spinal Cerebrospinal Fluid Leaks Disease by Computerized Image Processing.

    Science.gov (United States)

    Yıldırım, Mustafa S; Kara, Sadık; Albayram, Mehmet S; Okkesim, Şükrü

    2016-05-17

    Spontaneous Spinal Cerebrospinal Fluid Leaks (SSCFL) is a disease based on tears on the dura mater. Due to widespread symptoms and low frequency of the disease, diagnosis is problematic. Diagnostic lumbar puncture is commonly used for diagnosing SSCFL, though it is invasive and may cause pain, inflammation or new leakages. T2-weighted MR imaging is also used for diagnosis; however, the literature on T2-weighted MRI states that findings for diagnosis of SSCFL could be erroneous when differentiating the diseased and control. One another technique for diagnosis is CT-myelography, but this has been suggested to be less successful than T2-weighted MRI and it needs an initial lumbar puncture. This study aimed to develop an objective, computerized numerical analysis method using noninvasive routine Magnetic Resonance Images that can be used in the evaluation and diagnosis of SSCFL disease. Brain boundaries were automatically detected using methods of mathematical morphology, and a distance transform was employed. According to normalized distances, average densities of certain sites were proportioned and a numerical criterion related to cerebrospinal fluid distribution was calculated. The developed method was able to differentiate between 14 patients and 14 control subjects significantly with p = 0.0088 and d = 0.958. Also, the pre and post-treatment MRI of four patients was obtained and analyzed. The results were differentiated statistically (p = 0.0320, d = 0.853). An original, noninvasive and objective diagnostic test based on computerized image processing has been developed for evaluation of SSCFL. To our knowledge, this is the first computerized image processing method for evaluation of the disease. Discrimination between patients and controls shows the validity of the method. Also, post-treatment changes observed in four patients support this verdict.

  7. Skull and cerebrospinal fluid effects on microwave radiation propagation in human brain

    Science.gov (United States)

    Ansari, M. A.; Zarei, M.; Akhlaghipour, N.; Niknam, A. R.

    2017-12-01

    The determination of microwave absorption distribution in the human brain is necessary for the detection of brain tumors using thermo-acoustic imaging and for removing them using hyperthermia treatment. In contrast to ionizing radiation, hyperthermia treatment can be applied to remove tumors inside the brain without the concern of including secondary malignancies, which typically form from the neuronal cells of the septum pellucidum. The aim of this study is to determine the microwave absorption distribution in an adult human brain and to study the effects of skull and cerebrospinal fluid on the propagation of microwave radiation inside the brain. To this end, we simulate the microwave absorption distribution in a realistic adult brain model (Colin 27) using the mesh-based Monte Carlo (MMC) method. This is because in spite of there being other numerical methods, the MMC does not require a large memory, even for complicated geometries, and its algorithm is simple and easy to implement with low computational cost. The brain model is constructed using high-resolution (1 mm isotropic voxel) and low noise magnetic resonance imaging (MRI) scans and its volume contains 181×217×181 voxels, covering the brain completely. Using the MMC method, the radiative transport equation is solved and the absorbed microwave energy distribution in different brain regions is obtained without any fracture or anomaly. The simulation results show that the skull and cerebrospinal fluid guide the microwave radiation and suppress its penetration through deep brain compartments as a shielding factor. These results reveal that the MMC can be used to predict the amount of required energy to increase the temperature inside the tumour during hyperthermia treatment. Our results also show why a deep tumour inside an adult human brain cannot be efficiently treated using hyperthermia treatment. Finally, the accuracy of the presented numerical method is verified using the signal flow graph technique.

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

    NARCIS (Netherlands)

    Schade, Rogier P.; Schinkel, Janke; Roelandse, Freek W. C.; Geskus, Ronald B.; Visser, Leo G.; van Dijk, J. Marc C.; van Dijk, Marc C.; Voormolen, Joan H. C.; van Pelt, Hans; Kuijper, Ed J.

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  10. [External lumbar drainage with volumetric continuing infusion pump in patients with cerebrospinal fluid leak. A case series].

    Science.gov (United States)

    Manso Melgosa, Ana Belén; García Gutiérrez, Helena; Fernández Porras, Mónica; Castrillo Manero, Ana Berta; Pérez Marijuán, Belén

    To describe the incidence and complications arising in a number of cases of patients with cerebrospinal fluid leak treated by external lumbar drainage with infusion pump (IP) volumetric continuous from 2001 to 2014. Quantify cerebrospinal fluid leak closed by lumbar drainage with IP. Retrospective descriptive case series study. patients undergoing transsphenoidal pituitary surgery, Chiari surgery and laminectomy, that developed postoperative cerebrospinal fluid leak treated with continuous external lumbar drainage by IP. age, sex, type of intervention, variables related to the practice of the pump and complications. Average and medians were calculated for quantitative variables, frequencies and percentages for qualitative. Sample: 11 subjects. Incidence in running IP: disconnection, occlusion and acoustic alarm activation. Most frequently complication is headache; a case of pneumocephalus. The small number of subjects and the heterogeneity of these do not allow for comparison or establishing associations between variables. The resolution of the cerebrospinal fluid leak with continuous IP is lower in this study than others, and may be influenced by the small number of subjects. It should be noted the frequent activation of the pump alarm for no apparent cause. Protocol would be developed for preparing the IP team to reduce the acoustic alarm activation, and would make a prospective multicenter study. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid.

    Science.gov (United States)

    Kabanda, Taseera; Siedner, Mark J; Klausner, Jeffrey D; Muzoora, Conrad; Boulware, David R

    2014-01-01

    The cryptococcal antigen (CRAG) lateral flow assay (LFA) had 100% sensitivity and specificity on cerebrospinal fluid samples. Pretreatment LFA titers correlated with quantitative cultures (R(2) = 0.7) and predicted 2- and 10-week mortality. The CRAG LFA is an accurate diagnostic assay for CSF and should be considered for point-of-care diagnosis of cryptococcal meningitis.

  12. Baseline correlation and comparative kinetics of cerebrospinal fluid colony-forming unit counts and antigen titers in cryptococcal meningitis.

    NARCIS (Netherlands)

    Brouwer, A.E.; Teparrukkul, P.; Pinpraphaporn, S.; Larsen, R.A.; Chierakul, W.; Peacock, S.; Day, N.; White, N.J.; Harrison, T.S.

    2005-01-01

    Cerebrospinal fluid (CSF) cryptococcal colony-forming unit counts and CSF cryptococcal antigen titers serve as alternative measures of organism load in cryptococcal meningitis. For these measures, we correlated baseline values and rates of decline during the first 2 weeks of therapy in 68 human

  13. Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke

    DEFF Research Database (Denmark)

    Gredal, Hanne; Thomsen, Barbara B; Boza-Serrano, Antonio

    2017-01-01

    and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL...

  14. Cerebrospinal fluid levels of catecholamine metabolites in Parkinson’s disease and L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

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

    -dyskinetic PD patients and controls. Method: Cerebrospinal fluid (CSF) of 6 age-matched controls and 16 PD patients, (11 receiving levodopa, 6 dyskinetic and 6 not receiving levodopa), was analysed for catecholamines and metabolites by HPLC with electrochemical detection. Samples were collected after overnight...

  15. Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study

    DEFF Research Database (Denmark)

    Kruse, N.; Persson, S.; Alcolea, D.

    2015-01-01

    Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent...

  16. Changes in cerebrospinal fluid levels of vasopressin and oxytocin of the rat during various light-dark regimes

    NARCIS (Netherlands)

    Mens, W.B.J.; Andringa-Bakker, E.A.D.; Wimersma Greidanus, T.B. van

    1982-01-01

    Levels of arginine-vasopressin (AVP) and oxytocin (OXT) in cerebrospinal fluid (CSF) of rats were determined at various times of the day and the night under normal and changed light-dark conditions. During a regular daily 14 h and 10 h dark cycle (lights on 06.00 h, off 20.00 h), AVP in CSF

  17. EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors

    NARCIS (Netherlands)

    Milojkovic Kerklaan, B.; Pluim, Dick; Bol, Mijke; Hofland, Ingrid; Westerga, Johan; van Tinteren, Harm; Beijnen, Jos H; Boogerd, Willem; Schellens, Jan H M; Brandsma, Dieta

    BACKGROUND: Moderate diagnostic accuracy of MRI and initial cerebrospinal fluid (CSF) cytology analysis results in at least 10%-15% false negative diagnoses of leptomeningeal metastases (LM) of solid tumors, thus postponing start of therapy. The aim of this prospective clinical study was to

  18. Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions

    NARCIS (Netherlands)

    van Luijn, Marvin M.; van Meurs, Marjan; Stoop, Marcel P.; Verbraak, Evert; Wierenga-Wolf, Annet F.; Melief, Marie-Jose; Kreft, Karim L.; Verdijk, Robert M.; Hart, 't Bert A.; Luider, Theo M.; Laman, Jon D.; Hintzen, Rogier Q.

    Using proteomics, we previously identified chromogranin A (CgA) and clusterin (CLU) as disease-related proteins in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). CgA and CLU are involved in cell survival and are implicated in neurodegenerative disorders and may also have

  19. A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.

    Science.gov (United States)

    Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P; Alder, Hansjuerg; Carosi, Mariantonia A; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M

    2015-08-28

    Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications.

  20. Coconut Model for Learning First Steps of Craniotomy Techniques and Cerebrospinal Fluid Leak Avoidance.

    Science.gov (United States)

    Drummond-Braga, Bernardo; Peleja, Sebastião Berquó; Macedo, Guaracy; Drummond, Carlos Roberto S A; Costa, Pollyana H V; Garcia-Zapata, Marco T; Oliveira, Marcelo Magaldi

    2016-12-01

    Neurosurgery simulation has gained attention recently due to changes in the medical system. First-year neurosurgical residents in low-income countries usually perform their first craniotomy on a real subject. Development of high-fidelity, cheap, and largely available simulators is a challenge in residency training. An original model for the first steps of craniotomy with cerebrospinal fluid leak avoidance practice using a coconut is described. The coconut is a drupe from Cocos nucifera L. (coconut tree). The green coconut has 4 layers, and some similarity can be seen between these layers and the human skull. The materials used in the simulation are the same as those used in the operating room. The coconut is placed on the head holder support with the face up. The burr holes are made until endocarp is reached. The mesocarp is dissected, and the conductor is passed from one hole to the other with the Gigli saw. The hook handle for the wire saw is positioned, and the mesocarp and endocarp are cut. After sawing the 4 margins, mesocarp is detached from endocarp. Four burr holes are made from endocarp to endosperm. Careful dissection of the endosperm is done, avoiding liquid albumen leak. The Gigli saw is passed through the trephine holes. Hooks are placed, and the endocarp is cut. After cutting the 4 margins, it is dissected from the endosperm and removed. The main goal of the procedure is to remove the endocarp without fluid leakage. The coconut model for learning the first steps of craniotomy and cerebrospinal fluid leak avoidance has some limitations. It is more realistic while trying to remove the endocarp without damage to the endosperm. It is also cheap and can be widely used in low-income countries. However, the coconut does not have anatomic landmarks. The mesocarp makes the model less realistic because it has fibers that make the procedure more difficult and different from a real craniotomy. The model has a potential pedagogic neurosurgical application for

  1. Valproic acid increases cerebrospinal fluid zidovudine levels in a patient with AIDS.

    Science.gov (United States)

    Akula, S K; Rege, A B; Dreisbach, A W; Dejace, P M; Lertora, J J

    1997-04-01

    Valproic acid is an anticonvulsant drug known to inhibit the glucuronidation of zidovudine (AZT) in human liver microsomes. Zidovudine is metabolized by glucuronidation to the inactive 5'-glucuronide with a short plasma half-life (1.0 +/- 0.2 hour). This case presentation confirms that valproic acid inhibits glucuronidation in vivo, and this is the first documented observation of increased cerebrospinal fluid levels of zidovudine because of an interaction with valproic acid in a patient with acquired immune deficiency syndrome (AIDS). The peak plasma AZT level for the control period was 119 ng/mL, which increased almost 3-fold to 344 ng/mL with valproic acid (1.5 g/day). The plasma AZT trough was 47 ng/mL, which also increased almost 3-fold to 124 ng/mL with valproic acid. The molar ratio of plasma 5'-glucuronide/AZT at the peak was reduced from 1.77 (control) to 1.07 with valproic acid. The 5'-glucuronide/AZT ratio at the trough was reduced markedly from 5.0 (control) to 0.93 with valproic acid, suggesting in vivo inhibition of glucuronidation. Cerebrospinal AZT levels, drawn 30 minutes after peak plasma levels, increased from 27 ng/mL for the control to 47 ng/mL with valproic acid, which paralleled the change in peak plasma concentrations. This interaction with valproic acid may contribute to higher AZT levels in the brains of patients with human immunodeficiency virus-related (HIV) encephalopathy.

  2. Temporal Changes in the Cerebrospinal Fluid Level of Hypocretin-1 and Histamine in Narcolepsy.

    Science.gov (United States)

    Lopez, Régis; Barateau, Lucie; Evangelista, Elisa; Chenini, Sofiene; Robert, Philippe; Jaussent, Isabelle; Dauvilliers, Yves

    2017-01-01

    To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively. CSF hypocretin-1 (n = 6) and histamine/tele-methylhistamine (n = 5) levels were assessed twice (median interval: 14.4 months) in four patients with definite and in two with atypical cataplexy and hypocretin level greater than 100 pg/mL at baseline. CSF hypocretin levels decreased from normal/intermediate to undetectable levels in three of the four patients with definite cataplexy and remained stable in the other (>250 pg/mL). Hypocretin level decreased from 106 to 27 pg/mL in one patient with atypical cataplexy, and remained stable in the other (101 and 106 pg/mL). CSF histamine and tele-methylhistamine levels remained stable, but for one patient showing increased frequency of cataplexy and a strong decrease (-72.5%) of tele-methylhistamine levels several years after disease onset. No significant association was found between relative or absolute change in hypocretin level and demographic/clinical features. These findings show that in few patients with narcolepsy with cataplexy, symptoms and CSF marker levels can change over time. In these rare patients with cataplexy without baseline hypocretin deficiency, CSF markers should be monitored over time with potential for immune therapies in early stages to try limiting hypocretin neuron loss. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

  3. Amyloid-β oligomer detection by ELISA in cerebrospinal fluid and brain tissue.

    Science.gov (United States)

    Bruggink, Kim A; Jongbloed, Wesley; Biemans, Elisanne A L M; Veerhuis, Rob; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2013-02-15

    Amyloid-β (Aβ) deposits are important pathological hallmarks of Alzheimer's disease (AD). Aβ aggregates into fibrils; however, the intermediate oligomers are believed to be the most neurotoxic species and, therefore, are of great interest as potential biomarkers. Here, we have developed an enzyme-linked immunosorbent assay (ELISA) specific for Aβ oligomers by using the same capture and (labeled) detection antibody. The ELISA predominantly recognizes relatively small oligomers (10-25 kDa) and not monomers. In brain tissue of APP/PS1 transgenic mice, we found that Aβ oligomer levels increase with age. However, for measurements in human samples, pretreatment to remove human anti-mouse antibodies (HAMAs) was required. In HAMA-depleted human hippocampal extracts, the Aβ oligomer concentration was significantly increased in AD compared with nondemented controls. Aβ oligomer levels could also be quantified in pretreated cerebrospinal fluid (CSF) samples; however, no difference was detected between AD and control groups. Our data suggest that levels of small oligomers might not be suitable as biomarkers for AD. In addition, we demonstrate the importance of avoiding HAMA interference in assays to quantify Aβ oligomers in human body fluids. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Anna Koczula

    2017-02-01

    Full Text Available Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq. In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism. In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

  5. Quantification of the cerebrospinal fluid from a new whole body MRI sequence

    Science.gov (United States)

    Lebret, Alain; Petit, Eric; Durning, Bruno; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe

    2012-03-01

    Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinal fluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.

  6. Floating dural sac sign is a sensitive magnetic resonance imaging finding of spinal cerebrospinal fluid leakage

    International Nuclear Information System (INIS)

    Hosoya, Takaaki; Sato, Shinya; Kanoto, Masafumi; Kayama, Takamasa; Hatazawa, Jun; Fukao, Akira

    2013-01-01

    We would like to propose floating dural sac sign, which is observed as a hyperintense band or rim around the spinal dural sac on axial T 2 -weighted images, as a sensitive sign to identify cerebrospinal fluid (CSF) leakage. One hundred patients with orthostatic headache were prospectively registered in 11 hospitals. These patients were examined by brain magnetic resonance (MR) imaging (n=89), radioisotope cisternography (n=89), MR myelography (n=86), axial T 2 -weighted imaging of the spine (n=70), and computed tomography myelography (n=2). In this study, we separately evaluated the imaging findings of intracranial hypotension and spinal CSF leakage. Among 100 patients, 16 patients were diagnosed as having spinal CSF leaks. Of 70 patients examined with axial T 2 -weighted imaging, 14 patients were diagnosed with spinal CSF leaks, and floating dural sac sign was observed in 17 patients, 13 patients with spinal CSF leaks and 4 without CSF leaks (sensitivity 92.9%, specificity 92.9%). Of 86 patients examined by MR myelography, extradural fluid was observed in only 3 patients (sensitivity 21.4%, specificity 100%). The floating dural sac sign was a sensitive sign that can be used to identify CSF leakage. Spinal axial T 2 -weighted imaging might be a good screening method for spinal CSF leakage that can help to avoid the need for lumbar puncture. (author)

  7. Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles.

    Science.gov (United States)

    Siyahhan, Bercan; Knobloch, Verena; de Zélicourt, Diane; Asgari, Mahdi; Schmid Daners, Marianne; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2014-05-06

    While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation.

  8. Dinosaur Tail Sign: A Useful Spinal MRI Finding Indicative of Cerebrospinal Fluid Leakage.

    Science.gov (United States)

    Sakurai, Keita; Kanoto, Masafumi; Nakagawa, Motoo; Shimohira, Masashi; Tokumaru, Aya M; Kameyama, Masashi; Shimoji, Keigo; Morimoto, Satoru; Matsukawa, Noriyuki; Nishio, Minoru; Shibamoto, Yuta

    2017-06-01

    To evaluate the imaging characteristics and diagnostic utility of the "Dinosaur tail sign" in the diagnosis of cerebrospinal fluid (CSF) leakage. The authors propose the "Dinosaur tail sign," defined as a combination of the dorsal epidural hyperintensities, fat tissue, spinal cord, and cauda equine on lumbosacral sagittal fat-suppressed T2-weighted image (FST2WI), as a sensitive indicator for diagnosing CSF leakage. Imaging characteristics of the "Dinosaur tail sign" was evaluated in seven spontaneous intracranial hypotension (SIH) and 23 iatrogenic CSF leakage (ICSFL) patients. Additionally, the diagnostic index was compared between the "Dinosaur tail sign" and other previously reported useful magnetic resonance imaging (MRI) and magnetic resonance myelography (MRM) findings. In contrast to other imaging findings including the epidural expansion, floating dural sac sign, and distension of the spinal epidural veins on MRI, and paraspinal fluid collections (PFC) on MRM, the "Dinosaur tail sign" was found equally in both SIH and ICSFL patients (6 SIH and 19 ICSFL; 83% of all patients with CSF leakage). The "Dinosaur tail sign" showed sufficient diagnostic utility (sensitivity 83%, specificity 94%, accuracy 89%) that was comparable to that of PFC. The "Dinosaur tail sign" is a useful imaging finding suggestive of CSF leakage. Evaluation of subtle interspinous arched hyperintensities on spinal MRI is mandatory for the diagnosis of SIH and ICSFL. © 2017 American Headache Society.

  9. Alzheimer's Disease Cerebrospinal Fluid and Neuroimaging Biomarkers: Diagnostic Accuracy and Relationship to Drug Efficacy.

    Science.gov (United States)

    Khan, Tapan K; Alkon, Daniel L

    2015-01-01

    Widely researched Alzheimer's disease (AD) biomarkers include in vivo brain imaging with PET and MRI, imaging of amyloid plaques, and biochemical assays of Aβ 1 - 42, total tau, and phosphorylated tau (p-tau-181) in cerebrospinal fluid (CSF). In this review, we critically evaluate these biomarkers and discuss their clinical utility for the differential diagnosis of AD. Current AD biomarker tests are either highly invasive (requiring CSF collection) or expensive and labor-intensive (neuroimaging), making them unsuitable for use in the primary care, clinical office-based setting, or to assess drug efficacy in clinical trials. In addition, CSF and neuroimaging biomarkers continue to face challenges in achieving required sensitivity and specificity and minimizing center-to-center variability (for CSF-Aβ 1 - 42 biomarkers CV = 26.5% ; http://www.alzforum.org/news/conference-coverage/paris-standardization-hurdle-spinal-fluid-imaging-markers). Although potentially useful for selecting patient populations for inclusion in AD clinical trials, the utility of CSF biomarkers and neuroimaging techniques as surrogate endpoints of drug efficacy needs to be validated. Recent trials of β- and γ-secretase inhibitors and Aβ immunization-based therapies in AD showed no significant cognitive improvements, despite changes in CSF and neuroimaging biomarkers. As we learn more about the dysfunctional cellular and molecular signaling processes that occur in AD, and how these processes are manifested in tissues outside of the brain, new peripheral biomarkers may also be validated as non-invasive tests to diagnose preclinical and clinical AD.

  10. Cerebrospinal Fluid Indices in Acute Drug Intoxication; Do They Predict the Patients’ Outcome?

    Directory of Open Access Journals (Sweden)

    Mohammadreza Farsinejad

    2012-08-01

    Full Text Available Introduction: In some intoxicated patients, cerebrospinal fluid (CSF is examined due to the prolonged loss of consciousness, focal neurologic findings, and fever of unknown origin. We aimed to evaluate the probable relationship between the different toxicity causes and the CSF indices in poisoned patients and determine if they could predict the patients’ outcome. Methods: All patients who had been admitted to the toxicology intensive care unit of Loghman-Hakim hospital between March 2006 and March 2011 and had undergone lumbar puncture (LP were included into this retrospective study. The patients’ demographic data and results of CSF evaluation (level of glucose, lactate dehydrogenase, protein, and white blood cells in CSF fluid were evaluated. The data was analyzed using SPSS software version 17. Results: A total of 111 patients were evaluated. Mean age of the patients was 37±15 years. Thirteen (11.7% had deceased. No relation was found between the cause of poisoning (medication involved and the changes in CSF indices. A statistically significant difference was found between the survivors and non-survivors in terms of CSF protein, LDH, and WBC. However, such a difference was not detected between these two groups regarding CSF glucose. Conclusion: In intoxicated patients with prolonged decreased level of consciousness or prolonged fever, early evaluation of CSF can help early diagnosis of complications such as meningitis and prompt treatment. Also, high level of protein, LDH, and WBC in the CSF can predict higher mortality rates in these patients.

  11. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    Energy Technology Data Exchange (ETDEWEB)

    Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))

    1989-10-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-(14C)antipyrine and 2-(14C)deoxy-D-glucose method. The treatment induced moderate (15 days, base excess (BE) 16 mM) to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

  12. Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles

    Science.gov (United States)

    Siyahhan, Bercan; Knobloch, Verena; de Zélicourt, Diane; Asgari, Mahdi; Schmid Daners, Marianne; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2014-01-01

    While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation. PMID:24621815

  13. Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease.

    Science.gov (United States)

    Ghersi-Egea, Jean-François; Strazielle, Nathalie; Catala, Martin; Silva-Vargas, Violeta; Doetsch, Fiona; Engelhardt, Britta

    2018-03-01

    The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

  14. Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children.

    Science.gov (United States)

    Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

    2017-01-01

    To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone. Avaliar o papel da pesquisa de enterovírus no líquido cefalorraquidiano em comparação com o Escore de Meningite Bacteriana em crianças com meningite. Coorte retrospectiva, realizada pela análise de prontuários, incluindo pacientes pediátricos, com diagnóstico de meningite e atendidos em um hospital privado e terciário, localizado em São Paulo, entre 2011 e 2014. Foram excluídos os pacientes com doença crítica, púrpura, deriva

  15. Assessment of anatomic morphology of the connective structures among brain ventricles and cerebrospinal fluid movement in them by cerebrospinal fluid spin-labeling MRI

    International Nuclear Information System (INIS)

    Wang Ling; Shi Dapeng; Wang Ying; Liu Liya; Shen Hao

    2011-01-01

    Objective: To assess the anatomic morphology of the connective structures among brain ventricles and cerebrospinal fluid (CSF) movement in them by CSF spin-labeling MR imaging. Methods: According to the order of registration, 50 healthy volunteers were randomly selected and received cerebrospinal fluid spin-labeling MR scan with time-spatial labeling inversion recovery single-shot fast spin echo sequence (SLIR-SSFSE). The tagged CSF was used as an endogenous tracer. The anatomic morphology of the connective structures of brain ventricles and the flow direction of CSF were observed. The longitudinal diameter and transverse diameter of bilateral foramina of monro, midbrain aqueduct, and the central and bilateral lateral apertures of the fourth ventricle of each subject were measured and calculated based on multiple measurements. The flow rate of CSF was calculated based on the flow distance of CSF in the connective structures between brain ventricles during different TI time. The mean value of each indicator was acquired. Results: Two-way flow state of CSF was observed in all connective structures, including bilateral foramina of monro, midbrain aqueduct, and the central and bilateral lateral apertures of the fourth ventricle. On the coronal planes, foramen of monro appears as a 'Y'-type tubular structure locating among the both sides of the anteriomedial thalamus and fornix, which connect upward with bilateral lateral ventricles and downward with the third ventricle. The longitudinal diameter and transverse diameter of the left side of foramen of monro were 3.50-5.50 mm [mean (4.37±0.47) mm] and 1.00-1.40 mm [mean (1.21± 0.13) mm], respectively. The longitudinal diameter and transverse diameter of the right side of foramen of' monro were 4.20-4.80 mm [mean (4.42±0.20) mm] and 1.00-1.60 mm [mean (1.21± 0.19) mm], respectively. On the sagittal planes, foramen of monro appeared as an oblique fine tubular structure with the angle of 55°-58° between the both sides

  16. Research into the Physiology of Cerebrospinal Fluid Reaches a New Horizon: Intimate Exchange between Cerebrospinal Fluid and Interstitial Fluid May Contribute to Maintenance of Homeostasis in the Central Nervous System.

    Science.gov (United States)

    Matsumae, Mitsunori; Sato, Osamu; Hirayama, Akihiro; Hayashi, Naokazu; Takizawa, Ken; Atsumi, Hideki; Sorimachi, Takatoshi

    2016-07-15

    Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016.

  17. Application of neutron activation analysis and spectrophotometry for the determination of copper level in sera and cerebrospinal fluids of schizophrenic patients

    International Nuclear Information System (INIS)

    Lipcsey, A.; Fekete, J.; Oerdoegh, M.; Szabo, E.

    1985-01-01

    Neutron activation analysis and spectrophotometry were used for the determination of copper content in sera and cerebrospinal fluids of schizophrenic patients against control persons. Comparison of the results of copper determination by both methods is tabulated. From the data the following conclusions can be drawn: for copper determinations in sera the results of the two methods agree excellently. At small copper concentrations in the cerebrospinal fluids the deviations are rather high. It can also be seen that the copper contents determined from cerebrospinal fluids taken at different times are nearly equal. (author)

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

    International Nuclear Information System (INIS)

    Gottschalk, A.

    2015-01-01

    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), indium 111 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

  19. [Establishment of two-dimensional differential gel electrophoresis using cerebrospinal fluid from neurocysticercosis patients].

    Science.gov (United States)

    Li, Jing-Yi; Tian, Xiao-Jun; Huang, Yong; Yang, Yan-Jun; Ma, Qiao-Rong; Xue, Yan-Ping

    2008-06-30

    To establish the method of two-dimensional differential gel electrophoresis and obtain high resolution 2D images from cerebrospinal fluid (CSF) of patients with neurocysticercosis. CSF samples were collected from four patients diagnosed as neurocysticercosis clinically and by ELISA, computed tomography (CT) or magnetic resonance imaging (MRI), and from four healthy subjects without neurological disorders. The CSF samples were precipitated with cold acetone, then pooled by equal amount as patients and controls. The internal standard comprised equal amounts of proteins extracted from both groups. Internal standard, and proteins from the two groups were labeled prior to electrophoresis with spectrally resolvable fluorescent dyes, cyanein dye2 (Cy2), Cy3 and Cy5. Sodium dodecylsulfonate polyacrylamide gel chromatography (SDS-PAGE) and two-dimensional differential in-gel electrophoresis (2-D DIGE) of labeled samples were then run. The differential expressed proteins showed in the images of SDS-PAGE and 2-D DIGE gels scanned with 488 nm, 532 nm and 633 nm wavelength laser were analyzed by ImageQuant and DeCyde 5.0 respectively. Spot detection and quantification was performed for the differential in-gel analysis (DIA) module of DeCyder. Biological variation analysis (BVA) module of DeCyder was matched gel 1 and gel 2 images to provide data on differential protein expression levels between the two groups. The ImageQuant result displayed that the CSF protein was compatible with the dye, and the difference of protein amount was revealed by the difference of fluorescence intensity. DIA indicated that there were 896 and 894 protein dots on gel 1 and gel 2 respectively, and 90% of them were matched each other. BVA showed that there were 55 protein spots with different expressional level between neurocysticercosis and control groups. Protein spots with two-fold increase or decrease were 47 and 8 respectively in neurocysticercosis patients compared with healthy controls. The

  20. [Predictive value of cerebrospinal fluid lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation with blood-contaminated cerebrospinal fluid].

    Science.gov (United States)

    Wang, Yufang; Wang, Lingyan; Li, Jingchao; Shi, Lei; Yao, Mingli; Guan, Xiangdong; Ouyang, Bin

    2017-05-01

    To evaluate the diagnostic value of cerebrospinal lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation (PNBM) with blood-contaminated cerebrospinal fluid (CSF). A prospective observational study was conducted. 101 patients underwent neurosurgical operation and clinically suspected PNBM admitted to neurosurgical intensive care unit (NSICU) of the First Affiliated Hospital of Sun Yat-sen University from October 2015 to December 2016 were enrolled. Based on red blood cell quantitative test in CSF, the patients were divided into blood-contaminated and non blood-contaminated CSF groups. According to the PNBM diagnostic criteria of 2008 Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN), all patients were divided into PNBM group and non-PNBM group. The biochemical indexes levels in CSF were compared among the groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of CSF lactate for PNBM in blood-contaminated patients. A total of 101 suspected PNBM patients were enrolled. In 77 blood-contaminated CSF patients, 39 patients were diagnosed as PNBM (account for 50.6%); in 24 non-blood-contaminated patients, 12 patients were diagnosed as PNBM (account for 50.0%). (1) In non-PNBM patients, the lactate level in blood-contaminated CSF was significantly higher than that of non-blood-contaminated CSF (mmol/L: 3.5±1.3 vs. 2.3±1.1, P 0.05). (2) In both blood-contaminated and non blood-contaminated CSF, white blood cell (WBC), protein and lactate levels in PNBM group were significantly higher than those in non-PNBM group [WBC (×10 6 /L): 660.0 (67.5, 1 105.0) vs. 41.0 (15.0, 142.5) in blood-contaminated CSF, 168.0 (86.5, 269.5) vs. 34.5 (7.0, 83.5) in non-blood-contaminated CSF; protein (mg/L): 4 757.8 (2 995.2, 10 219.8) vs. 1 292.8 (924.2, 1 936.2) in blood-contaminated CSF, 39 247.3 (14 900.6, 62 552.2) vs. 1 441.6 (977.3, 2 963.9) in non blood

  1. Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL): a pediatric case report.

    Science.gov (United States)

    Gonçalves, Daniel; Meireles, Joana; Rocha, Ruben; Sampaio, Mafalda; Leão, Miguel

    2013-12-01

    The syndrome of transient headache and neurologic deficits associated with cerebrospinal fluid lymphocytosis (HaNDL) is characterized by 1 or more episodes of severe headache, transient neurologic deficits, and lymphocytic pleocytosis in the cerebrospinal fluid. It is a benign and self limited disorder seldom reported in pediatric age. We report the case of a 14-year-old girl who suffered from 2 episodes of headache with transient focal neurologic deficits and pleocytosis consistent with the syndrome of HaNDL. This entity should be taken into account as a differential diagnosis in otherwise healthy children presenting with recurrent headache and acute neurologic deficits. Repeated use of invasive and expensive laboratory and imaging investigations can be avoided when the diagnosis of the syndrome of HaNDL is correctly established.

  2. Case of acute meningitis with clear cerebrospinal fluid: value of computed tomography for the diagnosis of central nervous system tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Cesari, V.

    1986-11-06

    The author reports a case of acute meningitis with clear cerebrospinal fluid in which extensive bacteriologic investigations were negative making the etiologic diagnosis exceedingly difficult. Initiation of empiric antituberculous therapy was rapidly followed by clinical and biological improvement, without complications, and by resolution of abnormal findings on computed tomography of the brain. On these grounds, meningitis secondary to a tuberculoma in the temporal lobe was diagnosed. The author points out that tuberculous meningitis is still a severe, potentially fatal condition; this, together with the fact that tubercle bacilli are often very scarce or absent, requires that tuberculous meningitis be routinely considered in every patient with clear cerebrospinal fluid meningitis whose condition deteriorates. Computed tomography of the brain is essential to ensure rapid diagnosis and prompt initiation of antituberculous therapy. Lastly, the author points out that nowadays herpes simplex virus encephalopathy should also be considered.

  3. Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis

    Directory of Open Access Journals (Sweden)

    Jiwoon Choi

    2018-01-01

    Full Text Available Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.

  4. Cryptococcal meningitis associated with increased adenosine deaminase in the cerebrospinal fluid.

    Science.gov (United States)

    Tanaka, Yuji; Satomi, Kazuo

    2016-01-01

    Clinically, increased cerebrospinal fluid (CSF) adenosine deaminase (ADA) level is an important diagnostic clue of tuberculous meningitis. However, increased CSF ADA level can be caused by other neurological diseases. We report a case of a 67-year-old woman with cryptococcal meningitis presented with increased ADA level of the CSF. In parallel with her recovery, the ADA level of CSF decreased steadily. This is the first case described the chronological change in CSF ADA level of the patient with cryptococcal meningitis in detail. Clinically, increased CSF ADA level is an important diagnostic clue of tuberculous meningitis. However, previously, it was reported that increased CSF ADA level can be caused by other neurological diseases. In this case, the patient was diagnosed with cryptococcal meningitis, and the possibility of coinfection with tuberculous meningitis has been discarded by the negative PCR, negative cultures and the clinical course. In addition, the chronological change in CSF ADA level was useful for follow-up assessment. Cryptococcal meningitis should be considered for the differential diagnosis for diseases presented increased CSF ADA.

  5. Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis.

    Science.gov (United States)

    Choi, Jiwoon; Kim, Se Hoon

    2018-01-01

    Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4-11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.

  6. Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Elham Hashemi

    2017-01-01

    Full Text Available As the key producer of cerebrospinal fluid (CSF, the choroid plexus (CP provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2, as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.

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

    Directory of Open Access Journals (Sweden)

    Veening Jan G

    2012-08-01

    Full Text Available Abstract There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of β-endorphin (β-END, especially those involving the cerebrospinal fluid (CSF, as a message transport system to reach distant brain areas. The major source of β-END are the pro-opio-melano-cortin (POMC neurons, located in the arcuate hypothalamic nucleus (ARH, bordering the 3rd ventricle. In addition, numerous varicose β-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of β-END, independence of peripheral versus central levels, central β-END migration over considerable distances, behavioral effects of β-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain.

  8. Management of a posterior gunshot injury with a floating pedicle and cerebrospinal fluid leak.

    Science.gov (United States)

    Bourghli, Anouar; Abouhashem, Safwat; Abo Wali, Rami; Obeid, Ibrahim; Boissiere, Louis; Vital, Jean-Marc; Al Sarawan, Mohammed

    2018-03-10

    Gunshot injury to the spine can be devastating, and it has increased in the civilian population during the last decade. We present the case of a 30-year-old male, who received a bullet in his back after exchange of fire with the police. Initial assessment revealed paraparesis with cerebrospinal fluid leak (CSF) from the bullet entry hole, CT scan showed metal debris with two bullet fragments in the L5/S1 right foramen and lateral recess, and another fragment in the central canal posteriorly, and also it revealed two fracture lines creating a right L5 "floating pedicle". The patient was taken to the operating room and underwent L5/S1 posterior approach with right L5 pedicle stabilization with a pedicle screw, removal of the bullet fragments, dural repair with a patch, L5/S1 posterolateral fusion, and insertion of a lumbar CSF drain. The patient could walk with a walking frame on day 7 with a satisfactory radiological result at 1 year but with a remaining partial motor deficit of both ankles, mainly on the right side. Literature contains a lot of controversies regarding the management of spinal gunshot injuries. The current case shows that early surgical management, when partial neurological deficit with a CSF leak is noted, could improve the clinical outcome and prevent related complications.

  9. Flow cytometry and cytomorphology evaluation of hematologic malignancy in cerebrospinal fluids: comparison with retrospective clinical outcome.

    Science.gov (United States)

    Cesana, Clara; Klersy, Catherine; Scarpati, Barbara; Brando, Bruno; Faleri, Maurizio; Bertani, Giambattista; Gatti, Arianna; Volpato, Elisabetta; Barba, Claudia; Ferri, Ursula; Scampini, Linda; Grillo, Giovanni; Lando, Giuliana; Nosari, Annamaria; Morra, Enrica; Cairoli, Roberto

    2011-07-01

    An independent clinical assessment was compared with flow cytometry (FCM) and cytomorphology results obtained on 227 cerebrospinal fluids investigated for hematologic malignancy, in a retrospective longitudinal study with a median observation time of 11 months. A combined method assessment (CMA), defining "positive" a sample if at least one method gave "positive" results, was also tested. Eleven out of 55 screening samples and 53 out of 166 follow-up samples resulted positive at clinical evaluation. FCM and CM were concordant with positive clinical assessment in 68.5% and 51.5% of cases, respectively. According to CMA, 10.5% of samples (resulting false negative by either FCM or cytomorphology) were rescued as true positive. FCM retained significantly higher accuracy than cytomorphology (p=0.0065) and 100% sensitivity when at least 220 leukocytes were acquired. CMA accuracy was higher than FCM accuracy and significantly higher than cytomorphology accuracy in the analysis of all samples (p<0.0001), samples from mature B/T cell neoplasms (p=0.0021), and samples drawn after intrathecal treatment (p=0.0001). When acquiring ≤220 leukocytes, FCM accuracy was poor, and combining cytomorphology added statistically significant diagnostic advantage (p=0.0043). Although FCM is the best diagnostic tool for evaluating CSF, morphology seems helpful especially when clinically positive follow-up samples are nearly acellular.

  10. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

    Energy Technology Data Exchange (ETDEWEB)

    Miller, B.E.; Lipman, J.J.; Byrne, W.L.

    1987-12-07

    Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

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

    DEFF Research Database (Denmark)

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês

    2015-01-01

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

  12. Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients.

    Science.gov (United States)

    Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

    2016-11-14

    The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrP Sc ) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly.

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

    Science.gov (United States)

    Harbater, Osnat; Gannot, Israel

    2014-03-01

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

  14. Cerebrospinal fluid cytomorphologic findings in 41 intracranial tumors: a retrospective review

    Directory of Open Access Journals (Sweden)

    Maria José Sá

    1995-06-01

    Full Text Available The main objective of this retrospective review of clinical and cerebrospinal fluid (CSF data from 41 patients with intracranial tumors diagnosed between 1975 and 1989, is to report the role that the finding of neoplastic cells in CSF plays, specially when cerebral CT-scanning and MRI were not currently done. Another objective is to study the CSF proteic abnormalities in cerebral tumors. CSF cell count, cytomorphologic pictures obtained after sedimentation and protein findings are described. Tumor cells were seen in 12 cases (29%: medulloblastomas - 6, meningeal carcinomatosis - 3, multiforme glioblastoma - 1, ependymoma -1, cerebral metastasis -1; in two cases it was an unexpected finding. We noticed that tumoral localization next to the ventricles favoured cell exfoliation. Although pleocytosis was rare and uncorrelated with the presence of neoplastic cells, pathological cytomorphologic pictures appeared in most of the cases including all "positive" ones. Our results stress that the appearance of neoplastic cells in CSF remains helpful specially when it is an unexpected finding.

  15. miRNA Expression Profiles in Cerebrospinal Fluid and Blood of Patients with Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Sørensen, Sofie Sølvsten; Nygaard, Ann-Britt; Nielsen, Ming-Yuan

    2014-01-01

    in the cell-free fractions of CSF and blood were analyzed by a microarray technique (miRCURY LNA™ microRNA Array, Exiqon A/S, Denmark) using a quantitative PCR (qPCR) platform containing 378 miRNA primers. In total, 183 different miRNAs were detected in the CSF, of which two miRNAs (let-7c and miR-221-3p......The aims of the study were (1) to determine whether miRNAs (microRNAs) can be detected in the cerebrospinal fluid (CSF) and blood of patients with ischemic stroke and (2) to compare these miRNA profiles with corresponding profiles from other neurological patients to address whether the mi......RNA profiles of CSF or blood have potential usefulness as diagnostic biomarkers of ischemic stroke. CSF from patients with acute ischemic stroke (n = 10) and patients with other neurological diseases (n = 10) was collected by lumbar puncture. Blood samples were taken immediately after. Expression profiles...

  16. Biological changes of APA-BCC analgesic microcapsule in cerebrospinal fluid of patients with carcinomatous pain

    International Nuclear Information System (INIS)

    Luo Yun; Li Yanling; Xue Yilong; Guo Shulong; Gao Yuhong; Cui Xin

    2005-01-01

    To explore the changes of alginate-polylysine-alginate microcapsulated bovine adrenal medullary chromaffin cells (APA-BCC microcapsules) in morphology, survival rate and leucine- enkephalin secretion after they were transplanted into CSF of cancerpain patients, the APA- BCC microcapsules were Implanted into cavitas subarachnoidealis of cancer-pain patients by conventional lumbar puncture. After 7 or 8 days, cerebrospinal fluid was collected and the morphology of the APA-BCC microcapsule, the survival rate of cells were observed and secretory volume of leucine-enkephalin was assayed by radioimmunity method. Seven days after trans- plantation, the mean VAS decreased from 8.8 to 2.4, the survival rate of cells averagely reduced from 91.2% to 89.1%, morphology of APA-BCC microcapsules did not change obviously and secretory volume of leucine-enkephalin went up 1.65 times compared with that at pretrans- plantation. In conclusion, APA-BCC can survive, secret leucine-enkephalin and produce analgesic effect after transplanted into CSF of cancer-patients. (authors)

  17. Shedding of CD9 antigen into cerebrospinal fluid by acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Komada, Y; Ochiai, H; Shimizu, K; Azuma, E; Kamiya, H; Sakurai, M

    1990-07-01

    The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

  18. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome.

    Directory of Open Access Journals (Sweden)

    Steven E Schutzer

    2011-02-01

    Full Text Available Neurologic Post Treatment Lyme disease (nPTLS and Chronic Fatigue (CFS are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.Pooled cerebrospinal fluid (CSF samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS, coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01. CFS (n = 43 had 2,783 non-redundant proteins, nPTLS (n = 25 contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes.nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

  19. BAFF is decreased in the cerebrospinal fluid of multiple sclerosis at clinical onset.

    Science.gov (United States)

    Puthenparampil, M; Miante, S; Federle, L; Zanetta, C; Toffanin, E; Ruggero, S; Rinaldi, F; Gallo, P

    2016-08-15

    B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset. Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, QBAFF) and Index (QBAFF/QAlb, BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (pBAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (pBAFF index and IgGIF (r: -0.4, pBAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.

    Science.gov (United States)

    Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D

    1999-01-01

    We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis.

  1. Biodegradable Polymer Releasing Antibiotic Developed for Drainage Catheter of Cerebrospinal Fluid: In Vitro Results

    Science.gov (United States)

    Han, Song Yup; Cho, Ki Hong; Cho, Han Jin; An, Jeong Ho; Ra, Young Sin

    2005-01-01

    The authors developed a biodegradable polymer that releases an antibiotic (nalidixic acid) slowly and continuously, for prevention of catheter-induced infection during drainage of cerebrospinal fluid. We investigated the in vitro antibiotic releasing characteristics and bacterial killing effects of the new polymer against E. coli. The novel fluoroquinolone polymer was prepared using diisopropylcarbodiimide, poly (e-caprolactone) diol, and nalidixic acid. FT-IR, mass spectrometry, and elemental analysis proved that the novel antibacterial polymer was prepared successfully without any side products. Negative MS showed that the released drug has a similar molecular weight (M.W.=232, 350) to pure drug (M.W.=232). In high pressure liquid chromatography, the released drug and drug-oligomer showed similar retention times (about 4.5-5 min) in comparison to pure drug (4.5 min). The released nalidixic acid and nalidixic acid derivatives have antibacterial characteristics against E. coli, Staphylococcus aureus, and Salmonella typhi, of more than 3 months duration. This study suggests the possibility of applying this new polymer to manufacture drainage catheters that resist catheter-induced infection, by delivering antibiotics for a longer period of more than 1 month. PMID:15832004

  2. Simultaneous Detection of Five Pathogens from Cerebrospinal Fluid Specimens Using Luminex Technology

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    Linfu Zhou

    2016-02-01

    Full Text Available Early diagnosis and treatment are crucial for the outcome of central nervous system (CNS infections. In this study, we developed a multiplex PCR-Luminex assay for the simultaneous detection of five major pathogens, including Mycobacterium tuberculosis, Cryptococcus neoformans, Streptococcus pneumoniae, and herpes simplex virus types 1 and 2, which frequently cause CNS infections. Through the hybridization reaction between multiplex PCR-amplified targets and oligonucleotide “anti-TAG” sequences, we found that the PCR-Luminex assay could detect as low as 101–102 copies of synthetic pathogen DNAs. Furthermore, 163 cerebrospinal fluid (CSF specimens from patients with suspected CNS infections were used to evaluate the efficiency of this multiplex PCR-Luminex method. Compared with Ziehl-Neelsen stain, this assay showed a high diagnostic accuracy for tuberculosis meningitis (sensitivity, 90.7% and specificity, 99.1%. For cryptococcal meningitis, the sensitivity and specificity were 92% and 97.1%, respectively, compared with the May Grunwald Giemsa (MGG stain. For herpes simplex virus types 1 and 2 encephalitis, the sensitivities were 80.8% and 100%, and the specificities were 94.2% and 99%, respectively, compared with Enzyme Linked Immunosorbent Assay (ELISA assays. Taken together, this multiplex PCR-Luminex assay showed potential efficiency for the simultaneous detection of five pathogens and may be a promising supplement to conventional methods for diagnosing CNS infections.

  3. Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome.

    Science.gov (United States)

    Meya, David B; Okurut, Samuel; Zziwa, Godfrey; Rolfes, Melissa A; Kelsey, Melander; Cose, Steve; Joloba, Moses; Naluyima, Prossy; Palmer, Brent E; Kambugu, Andrew; Mayanja-Kizza, Harriet; Bohjanen, Paul R; Eller, Michael A; Wahl, Sharon M; Boulware, David R; Manabe, Yuka C; Janoff, Edward N

    2015-05-15

    Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood. We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10). At diagnosis, highly activated CD8(+) T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4(+) T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood. After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4(+) T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  4. Spontaneous recovery of post-traumatic cerebrospinal fluid rhinorrhea following meningitis: A case report.

    Science.gov (United States)

    Citisli, Veli; Kocaoglu, Murat; Necan, Ceyda; İbrahimoglu, Muhammet; Celiker, Özkan; Baykara, Eyüp; Ozdemir, Mevci; Acar, Feridun; Coskun, Mehmet Erdal

    2015-04-01

    The aim of the present report was to present the patient with an anterior cranial base fracture who developed post-traumatic cerebrospinal fluid rhinorrhea, which recovered after onset of meningitis complication. A 26-year-old male patient who had a traffic accident one week ago was sent to our clinic because of his rhinorrhea persisting for 4 days. On cranial computed tomography, fracture of the left frontal skull base and sinus walls, a fracture line on temporal bone, parenchymal bleeding in the vicinity of the frontal sinus, subarachnoidal bleeding and left temporal extradural hematoma were detected. Then he underwent sinus wall repair and extradural hematoma was drained through bifrontal craniotomy. However, rhinorrhea persisted which resulted a deterioration in consciousness and he entered into a deep somnolent state. When his symptoms of meningitis became apparent, rhinorrhea of the patient disappeared. The patient transferred in intensive care unit and re-connected to a lumbar drainage system. On cerebral magnetic resonance imaging, regression of contrast-enhanced lesions localized in the left anterotemporal and frontal and in the regions lateral to the right trigon and medial to the right thalamus and in the right posteroparietal regions was observed. Despite repair of the anterior cranial fracture and lumbar drainage, rhinorrhea may persist. Herein, development of meningitis caused disappearing of rhinorrhea symptoms without any need for surgical intervention.

  5. The clinical value of Hawkeye SPECT fusion imaging in diagnosis and localization of cerebrospinal fluid rhinorrhea

    International Nuclear Information System (INIS)

    Zhang Guoxu; Wang Zhiguo; Hao Shanhu; Zhang Tong; Che Xianying

    2009-01-01

    Objective: The purpose of this study was to evaluate the clinical value of the 99 Tc m -DTPA cerebrospinal fluid (CSF) Hawkeye SPECT fusion imaging for diagnosing and localizing CSF rhinorrhea (CSFR). Methods: Thirty-three patients with suspected CSFR were included in this study. All cases un-derwent planar and SPECT and CT imaging at 120 and 180 min, respectively, after 99 Tc m -DTPA injection via lumbar puncture before surgery treatment. The location and path of CSF leakage were diagnosed on pla-nar and SPECT fusion imaging. SAS 6.12 software was used to analyze both sets of imaging data, and the χ 2 test was used to compare the results from planar imaging with those of SPECT fusion imaging. Results: In 33 patients with CSFR, 31 abnormally concentrated radionuclide activity and location of leakage were founded on SPECT fusion imaging, whereas 30 of such abnormalities were detected by planar imaging. All CSFR cases were confirmed by surgery afterwards. The sensitivity and accuracy for diagnosing and localizing CSFR were 93.9% (31/33), 90.9% (30/33) in SPECT fusion imaging and 93.5% (29/31), 78.3% (18/23) in planar imaging. Conclusion: 99 Tc m -DTPA CSF Hawkeye SPECT fusion imaging is an efficient, simple and accurate method for diagnosing and localizing CSF leakage. (authors)

  6. Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus.

    Science.gov (United States)

    Andescavage, Nickie N; DuPlessis, Adre; McCarter, Robert; Vezina, Gilbert; Robertson, Richard; Limperopoulos, Catherine

    2016-01-01

    The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus. We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting volumes according to gestational age and described the relative development of CSF to fetal brain parenchyma. Each CSF space demonstrated major increases in volumetric growth during the second half of gestation: third ventricle (23-fold), extra-axial CSF (11-fold), fourth ventricle (8-fold), and lateral ventricle (2-fold). Total CSF volume was related to total brain volume (p development detected on fetal screening using neurosonography. Normative values of absolute CSF volume, as well as relative growth in comparison to intracranial parenchyma, provide valuable insight into normal fetal neurodevelopment. These data may provide important biomarkers of early deviations from normal growth, better distinguish between benign variants and early disease, and serve as reference standards for postnatal growth and development in the premature infant. © 2017 S. Karger AG, Basel.

  7. Relationship between Severity of Aseptic Meningitis and Cerebrospinal Fluid Cytokine Levels.

    Science.gov (United States)

    Hikita, Norikatsu; Seto, Toshiyuki; Yamashita, Kanako; Iritani, Nobuhiro; Aata, Minoru; Ogura, Hisashi; Shintaku, Haruo

    2015-12-01

    Pediatricians sometimes see patients with severe aseptic meningitis and prolonged fever or severe headache, or both. This condition generally has a good prognosis and is usually treated with supportive therapy. However, there is neither guideline nor consensus for the treatment of patients with severe aseptic meningitis. Here, we investigated the relationship between disease severity and biomarkers. The subjects were 32 children aged 0 to 14 years, 23 of whom had aseptic meningitis and 9 of whom were meningitis-free controls. Aseptic meningitis was retrospectively categorized into two subgroups, namely mumps meningitis (MM) and viral meningitis excluding that caused by mumps (EM). We defined a novel aseptic meningitis severity score (AMSS) from the signs and symptoms of aseptic meningitis and thus evaluated disease severity. We analyzed the profiles of cytokines in the patients' cerebrospinal fluid (CSF). The AMSS in MM was significantly higher than that in EM. IL-4, IL-6, IL-8, IL-10, and G-CSF levels in MM and EM CSF were higher than those in control CSF. IFN-γ levels were higher in MM than in controls (p<0.01). IL-10 and IFN-γ levels in MM were higher than those in EM. MM was more severe than EM. One likely reason is the higher CSF cytokine levels in MM. IFN-γ may be a potentially strong biomarker of MM severity. Our findings would help further understanding

  8. Detection Of Haemophilus Influenzae Type B In Cerebrospinal Fluid Of Suspected Children With Meningitis Bypcr

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    F.A. Nakhjavani

    2005-08-01

    Full Text Available A polymerase chain reaction (PCR assay with primers from "hpd" gene was compared with culture for the detection of Haemophilus influenzae type b (Hib in CSF samples from children suspected of meningitis.Methods: 300 cerebrospinal fluid (CSF samples from suspected meningitis cases were studied by culture (Leventhal & Chocolate Agar and PCR.Results: The latter method could detect Hib in all 5 culture positive and in 2 of 295 culture negative cases, showing sensitivity, specificity, and an accuracy index of 100%, 99% and 99%, espectively. The PCR result was available within a day.Conclusion: This study has shown that PCR is a rapid, sensitive, and specific diagnostic test for Hib from CSF samples. Futthermore, to maximize management of meningitis cases to reduce the morbidity, mortality, and complications of invasive Hib infection a combination of culture and PCR is necessary for the detection ofHib infection. The incidence ofHib meningitis among children in Children's Medical Center in Tehran based on culture and PCR results were 2.4% and 1.7% respectively. Based on culture results, Hib causes 15.6% of all cases ofbacte1ial meningitis in children.

  9. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

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    Vis, J.B. de; Zwanenburg, J.J.; Kleij, L.A. van der; Spijkerman, J.M.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Biessels, G.J. [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Petersen, E.T. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Hvidovre Hospital, Danish Research Centre for Magnetic Resonance, Hvidovre (Denmark)

    2016-05-15

    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T{sub 2} of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T{sub 1}-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (V{sub CSF}) and the T{sub 2} of CSF (T{sub 2,CSF}) was calculated. The correlation between V{sub CSF} / T{sub 2,CSF} and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular V{sub CSF} increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T{sub 2} of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T{sub 2} of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. (orig.)

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

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    Sérgio Monteiro de Almeida

    2014-07-01

    Full Text Available Increased plasma lactate levels can indicate the presence of metabolic disorders in HIV infected individuals. Objective: To determine whether a portable analyzer is valid for measuring cerebrospinal fluid (CSF and plasma lactate levels in HIV infected individuals. Method: CSF and plasma were collected from 178 subjects. Samples tested by the Accutrend® portable analyzer were compared to those tested by a reference device (SYNCHRON LX® 20. Results: The portable analyzer had in plasma sensitivity of 0.95 and specificity 0.87. For CSF the specificity was 0.95; the sensitivity 0.33; the negative predictive value was 95% and the positive predictive value 33%. Conclusions: These findings support the validity of the portable analyzer in measuring lactate concentrations in CSF that fall within the normal range. The relatively poor positive predictive value indicates that a result above the reference range may represent a “false positive test”, and should be confirmed by the reference device before concluding abnormality.

  11. Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein

    Science.gov (United States)

    Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

    2015-01-01

    Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1–4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis. PMID:26509880

  12. Intracranial repair of posttraumatic cerebrospinal fluid rhinorrhea associated with recurrent meningitis.

    Science.gov (United States)

    Yaldiz, Can; Ozdemir, Nail; Yaman, Onur; Seyin, İsmail Ertan; Oguzoglu, Serdar

    2015-01-01

    The purposes of this study are to assess the efficacy of our intracranial surgery and evaluate the association between failure after first surgical repair and the risk factors that have been applied on a group of 13 patients affected by posttraumatic cerebrospinal fluid rhinorrhea associated with recurrent meningitis. We retrospectively collected data on 13 patients referred to our institution. All patients had history of head trauma and experienced 2 or more episodes of meningitis. Three of the 13 patients had craniectomy defect due to previous trauma and surgery, 9 patients had linear fracture, and 1 patient had no apparent fracture line on preoperative radiologic evaluation. Ten of the 13 patients had identified frontal bone fracture involving the frontal sinus during surgery. Dural tear was identified intradurally and was repaired using a fascia lata graft with or without fibrin glue. Fibrin glue was applied over the suture in 7 patients. Three of the 13 patients had large dural defects. The size of bone and dural defect seems to be an important prognostic factor of episodes of meningitis. The use of fibrin glue to fixate fascia lata graft did not benefit the outcome.

  13. A Three years retrospective analysis of agents isolated from cerebrospinal fluid in a University Hospital

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    Barış Otlu

    2012-03-01

    Full Text Available Objectives: In this study, we aimed to investigate the agents which were isolated from cerebrospinal fluid (CSF samples in our hospital for three years, retrospectively.Materials and methods: The CSF samples, which were sent our laboratory, of the patients those had presumptive diagnosis of meningitis between September 2008 and September 2011 were included into the study. Isolated bacteria were identified with conventional methods, biochemical tests and/or Phonix (BD, US kits. Antimicrobial susceptibility of the strains were investigated according to Clinical Laboratory Standards Institute (CLSI recommendations.Results: 11 Streptococcus pneumoniae, 8 Klebsiella pneumoniae, 7 Pseudomonas aeruginosa, 7 Acinetobacter baumannii, 5 Escherichia coli, 4 Enterococcus spp., 2 Enterobacter spp., 25 Coagulase-negative staphylococcus, 1 Morganella morganii, 2 Neisseria meningitidis, 1 Brucella spp., and 1 Candida albicans were isolated (overall n:74; 5.2% from total 1408 CSF samples. In susceptibility test, 2 S.pneumonia was found as penicillin-resistant, and one E.coli and two K.pneumoniae were found as extended spectrum of beta-lactamase producers. Additionally, carbapenem resistance was detected in three A.baumannii and one P.aeruginosa strains.Conclusion: Determination of agent profile and antimicrobial resistance pattern from different localizations and patients’ groups will help to improve protective and therapeutic health policies.

  14. Sandwich wound closure reduces the risk of cerebrospinal fluid leaks in posterior fossa surgery

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    Verena Heymanns

    2016-07-01

    Full Text Available Posterior fossa surgery is demanding and hides a significant number of obstacles starting from the approach to the wound closure. The risk of cerebrospinal fluid (CSF leakage in posterior fossa surgery given in the literature is around 8%. The present study aims to introduce a sandwich closure of the dura in posterior fossa surgery, which reduces significantly the number of CSF leaks (3.8% in the patients treated in our department. Three hundred and ten patients treated in our hospital in the years 2009-2013 for posterior fossa pathologies were retrospectively evaluated. The dura closure method was as following: lyophilized dura put under the dura and sealed with fibrin glue and sutures, dura adapting stitches, TachoSil® (Takeda Pharma A/S, Roskilde, Denmark, Gelfoam® (Pfizer Inc., New York, NY, USA and polymethylmethacrylate (osteoclastic craniotomy. The incidence of postsurgical complications associated with the dural closure like CSF leakage, infections, bleeding is evaluated. Only 3.8% of patients developed CSF leakage and only 0.5% needed a second surgery for CSF leakage closure. Two percent had a cerebellar bleeding with no need for re-operation and 3% had a wound infection treated with antibiotics. The sandwich wound closure we are applying for posterior fossa surgery in our patients correlates with a significant reduction of CSF leaks compared to the literature.

  15. Detection of free immunoglobulin light chains in cerebrospinal fluids of patients with central nervous system lymphomas.

    Science.gov (United States)

    Schroers, Roland; Baraniskin, Alexander; Heute, Christoph; Kuhnhenn, Jan; Alekseyev, Andriy; Schmiegel, Wolff; Schlegel, Uwe; Pels, Hendrik-Johannes

    2010-09-01

    Diagnosis of central nervous system (CNS) lymphoma depends on histopathology of brain biopsies, because no reliable disease marker in the cerebrospinal fluid (CSF) has been identified yet. B-cell lymphomas such as CNS lymphomas are clonally restricted and express either kappa or lambda immunoglobulin light chains. The aim of this study was to find out a potential diagnostic value of free immunoglobulin light chains released into the CSF of CNS lymphoma patients. Kappa (kappa) and lambda (lambda) free immunoglobulin light chains (FLC) were measured in CSF and serum samples collected from 21 patients with primary and secondary CNS lymphomas and 14 control patients with different neurologic disorders. FLC concentrations and ratios were compared between patient groups and were further analyzed in correlation with clinical, cytopathological, and radiological findings. FLC concentrations for all patients were lower in CSF when compared to serum. In patients with CNS lymphoma, the FLC ratios in CSF were higher (range 392-0.3) compared to control patients (range 3.0-0.3). Irrespective of cytopathological proven lymphomatous meningitis, in 11/21 lymphoma CSF samples the FLC ratios were markedly above 3.0 indicating a clonally restricted B-cell population. Increased FLC ratios in CSF were found in those patients showing subependymal lymphoma contact as detected in magnetic resonance imaging. In summary, this is the first report demonstrating that a significant proportion of patients with CNS lymphomas display a markedly increased FLC ratio in the CSF.

  16. Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children.

    Science.gov (United States)

    Nazir, Mudasir; Wani, Wasim Ahmad; Malik, Muzaffar Ahmad; Mir, Mohd Rafiq; Ashraf, Younis; Kawoosa, Khalid; Ali, Syed Wajid

    To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. At a cut-off value of 3mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2mmol/L. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  17. Ethmoidal encephalocele associated with cerebrospinal fluid fistula: indications and results of mini-invasive transnasal approach.

    Science.gov (United States)

    Fraioli, Mario Francesco; Umana, Giuseppe Emanuele; Fiorucci, Giulia; Fraioli, Chiara

    2014-03-01

    Anterior skull base defects with encephalocele in adults are quite rare and can be a cause of spontaneous rhinoliquorrhea; however, cerebrospinal fluid (CSF) fistula can be not rarely misdiagnosed for several months or years. Five adult patients affected by ethmoidal encephalocele with CSF fistula were treated in our institute from 2006 through to 2011. Onset of clinical history was represented by rhinoliquorrhea, which was precociously recognized in only 1 patient; in the other 4, it was misdiagnosed for a period ranging from 11 months to 5 years. After clinical diagnosis of CSF fistula and after brain magnetic resonance imaging, ethmoidal encephalocele was evident in all patients; preoperative study was completed by spiral computed tomography scan, to clearly identify the skull base bone defect. All patients were operated on by transsphenoidal endonasal endoscope-assisted microsurgical approach through 1 nostril. The herniated brain was coagulated and removed, and reconstruction of cranial base was performed. Postoperative rhinoliquorrhea or other complications did not occur in any patient at short and late follow-up. All patients were discharged after a few days. Endonasal endoscope-assisted microsurgical approach was effective in exposing and repairing the ethmoidal bone defect; tridimensional vision and wide lateral and superior exposition of the operative field were possible in each patient, thanks to the use of microscope and angulated endoscope.

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

    Science.gov (United States)

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

    1999-01-01

    The diagnosis of human neurobrucellosis usually relies on the detection of antibodies to Brucella lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) by agglutination tests or enzyme-linked immunosorbent assay (ELISA). Here we describe the detection of immunoglobulin G (IgG) to cytoplasmic proteins (CP) of Brucella spp. by ELISA and Western blotting in seven CSF samples from five patients with neurobrucellosis. While IgG to CP (titers of 200 to 12,800) and IgG to LPS (800 to 6,400) were found in the CSF of these patients, these antibodies were not detected in CSF samples from two patients who had systemic brucellosis without neurological involvement. The latter, however, had serum IgG and IgM to both LPS and CP. No reactivity to these antigens was found in CSF samples from 14 and 20 patients suffering from nonbrucellar meningitis and noninfectious diseases, respectively. These findings suggest that, in addition to its usefulness in the serological diagnosis of human systemic brucellosis, the ELISA with CP antigen can be used for the specific diagnosis of human neurobrucellosis. PMID:10473531

  19. Cerebrospinal fluid image segmentation using spatial fuzzy clustering method with improved evolutionary Expectation Maximization.

    Science.gov (United States)

    Abdullah, Afnizanfaizal; Hirayama, Akihiro; Yatsushiro, Satoshi; Matsumae, Mitsunori; Kuroda, Kagayaki

    2013-01-01

    Visualization of cerebrospinal fluid (CSF), that flow in the brain and spinal cord, plays an important role to detect neurodegenerative diseases such as Alzheimer's disease. This is performed by measuring the substantial changes in the CSF flow dynamics, volume and/or pressure gradient. Magnetic resonance imaging (MRI) technique has become a prominent tool to quantitatively measure these changes and image segmentation method has been widely used to distinguish the CSF flows from the brain tissues. However, this is often hampered by the presence of partial volume effect in the images. In this paper, a new hybrid evolutionary spatial fuzzy clustering method is introduced to overcome the partial volume effect in the MRI images. The proposed method incorporates Expectation Maximization (EM) method, which is improved by the evolutionary operations of the Genetic Algorithm (GA) to differentiate the CSF from the brain tissues. The proposed improvement is incorporated into a spatial-based fuzzy clustering (SFCM) method to improve segmentation of the boundary curve of the CSF and the brain tissues. The proposed method was validated using MRI images of Alzheimer's disease patient. The results presented that the proposed method is capable to filter the CSF regions from the brain tissues more effectively compared to the standard EM, FCM, and SFCM methods.

  20. Simulated spinal cerebrospinal fluid leak repair: an educational model with didactic and technical components.

    Science.gov (United States)

    Ghobrial, George M; Anderson, Paul A; Chitale, Rohan; Campbell, Peter G; Lobel, Darlene A; Harrop, James

    2013-10-01

    In the era of surgical resident work hour restrictions, the traditional apprenticeship model may provide fewer hours for neurosurgical residents to hone technical skills. Spinal dura mater closure or repair is 1 skill that is infrequently encountered, and persistent cerebrospinal fluid leaks are a potential morbidity. To establish an educational curriculum to train residents in spinal dura mater closure with a novel durotomy repair model. The Congress of Neurological Surgeons has developed a simulation-based model for durotomy closure with the ongoing efforts of their simulation educational committee. The core curriculum consists of didactic training materials and a technical simulation model of dural repair for the lumbar spine. Didactic pretest scores ranged from 4/11 (36%) to 10/11 (91%). Posttest scores ranged from 8/11 (73%) to 11/11 (100%). Overall, didactic improvements were demonstrated by all participants, with a mean improvement between pre- and posttest scores of 1.17 (18.5%; P = .02). The technical component consisted of 11 durotomy closures by 6 participants, where 4 participants performed multiple durotomies. Mean time to closure of the durotomy ranged from 490 to 546 seconds in the first and second closures, respectively (P = .66), whereby the median leak rate improved from 14 to 7 (P = .34). There were also demonstrative technical improvements by all. Simulated spinal dura mater repair appears to be a potentially valuable tool in the education of neurosurgery residents. The combination of a didactic and technical assessment appears to be synergistic in terms of educational development.

  1. Interference of Cerebrospinal Fluid Total Protein Measurement by Povidone-Iodine Contamination

    Science.gov (United States)

    Gounden, Verena; Sacks, David B; Zhao, Zhen

    2014-01-01

    Background A falsely high cerebrospinal fluid (CSF) total protein (TP) result measured by pyrogallol red (PGR) method was suspected to be caused by preparation of the collection site with povidone-iodine (PVP-iodine) solution. Methods CSF TP was evaluated for interference in samples with different final concentrations of PVP-iodine (up to 0.25% PVP and 0.025% iodine) or iodine alone (up to 0.025% iodine) using three methods: PGR, modified biuret and benzethonium chloride (BZTC). Interference exceeding ±20% of the baseline value is considered clinically significant according the criterion defined by College of American Pathologists. Results There was a positive interference with the PGR method and a negative inference for the BZTC method in CSF samples spiked with PVP-iodine. The PVP-iodine (up to 0.25% PVP and 0.025% iodine) did not cause a clinically significant interference with the modified biuret method. PVP alone without iodine caused a positive interference with the PGR method but did not interfere with the modified biuret or the BZTC method. When the samples were spiked with iodine alone, none of the three methods was affected (change < 20%) by iodine concentration up to 0.025%. Conclusions Contamination of CSF specimens with PVP-iodine can lead to interference with CSF TP measurements using PGR or BZTC methods. PMID:25446880

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

    International Nuclear Information System (INIS)

    Samuel, A.M.; Dhalla, A.S.; Mazarello, T.

    1986-01-01

    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)

  3. Interference of cerebrospinal fluid total protein measurement by povidone-iodine contamination.

    Science.gov (United States)

    Gounden, Verena; Sacks, David B; Zhao, Zhen

    2015-02-02

    A falsely high cerebrospinal fluid (CSF) total protein (TP) result measured by pyrogallol red (PGR) method was suspected to be caused by preparation of the collection site with povidone-iodine (PVP-iodine) solution. CSF TP was evaluated for interference in samples with different final concentrations of PVP-iodine (up to 0.25% PVP and 0.025% iodine) or iodine alone (up to 0.025% iodine) using three methods: PGR, modified biuret and benzethonium chloride (BZTC). Interference exceeding ±20% of the baseline value is considered clinically significant according to the criterion defined by the College of American Pathologists. There were positive interference with the PGR method and negative inference for the BZTC method in CSF samples spiked with PVP-iodine. The PVP-iodine (up to 0.25% PVP and 0.025% iodine) did not cause a clinically significant interference with the modified biuret method. PVP alone without iodine caused a positive interference with the PGR method but did not interfere with the modified biuret or the BZTC method. When the samples were spiked with iodine alone, none of the three methods was affected (change<20%) by iodine concentration up to 0.025%. Contamination of CSF specimens with PVP-iodine can lead to interference with CSF TP measurements using PGR or BZTC methods. Published by Elsevier B.V.

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

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

    2013-12-13

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

  5. Cerebrospinal fluid hypocretin 1 deficiency, overweight, and metabolic dysregulation in patients with narcolepsy.

    Science.gov (United States)

    Heier, Mona S; Jansson, Tine S; Gautvik, Kaare M

    2011-12-15

    The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls. 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls. Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups. The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms.

  6. Cerebrospinal fluid hypocretin-1 levels during the active period of cluster headache.

    Science.gov (United States)

    Cevoli, Sabina; Pizza, Fabio; Grimaldi, Daniela; Nicodemo, Marianna; Favoni, Valentina; Pierangeli, Giulia; Valko, Philipp O; Baumann, Christian R; Montagna, Pasquale; Bassetti, Claudio L; Cortelli, Pietro

    2011-06-01

    Hypocretins (orexins) are hypothalamic neuropeptides which are involved in a wide range of physiological processes in mammals including central pain processing. Genetic studies in humans evidenced a role for the hypocretinergic system in cluster headache (CH). We tested cerebrospinal fluid (CSF) hypocretin-1 (orexin-A) levels in 10 CH patients during an active cluster period. CSF hypocretin-1 levels were measured by radioimmunoassay. CSF hypocretin-1 levels were within the normal range (mean 457.3±104.98 pg/ml, range 304-639) in our 10 patients, with a slight reduction in one case (304 pg/ml). There were no associations between CSF hypocretin-1 levels and the clinical features of CH. A trend towards higher hypocretin-1 levels was disclosed in patients with chronic CH compared to episodic CH. CSF hypocretin-1 levels seem not to influence the clinical course of CH, but our results cannot completely exclude a functional involvement of the hypothalamic hypocretinergic system in the pathogenesis of CH.

  7. Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Bettina Kuenz

    Full Text Available BACKGROUND: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS. METHODOLOGY/PRINCIPAL FINDINGS: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS, relapsing-remitting (RR and chronic progressive (CP MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138- and plasma blasts (CD19+CD138+ in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP-9 and the B cell chemokine CxCL-13. CONCLUSIONS: Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS.

  8. Diffusion-Weighted Magnetic Resonance Imaging of Cerebrospinal Fluid in Patients with and without Communicating Hydrocephalus

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    Nasel, C.; Gentzsch, S.; Heimberger, K. [Cerebrovascular Imaging Workgroup of the Div. of Neuroradiology, Dept. of Radiology, Medical Univ. Vienna, Vienna (Austria)

    2007-09-15

    Background: Recent concepts about cerebrospinal fluid (CSF) circulation in communicating hydrocephalus (CoHy), which is also termed 'restricted arterial pulsation hydrocephalus,' suggest reduced arterial pulsations of subarachnoid vessels with a smaller amount of CSF shifted in subarachnoid spaces during the early systole. The postulated restriction of subarachnoid arterial pulsations in CoHy should induce a smaller motion artifact and reduced local stream effects in CSF in magnetic resonance (MR) diffusion-weighted imaging (DWI). Purpose: To investigate the maximum diffusivity in CSF in patients with and without CoHy using DWI. Material and Methods: 12 patients without CSF circulation disturbances and six cases with proven CoHy were assessed. Diffusion was measured in six non collinear directions without triggering the arterial pulse wave (scan time 6:45 min, voxel size 2x2x2 mm). Due to expected artifacts, the calculated maximum diffusivity was called apparent diffusivity. Regional high and low apparent diffusivity was assessed in CSF spaces on newly created 3D CSF motion maps. Results: Patients with regular CSF circulation exhibited high apparent diffusivity in CSF in basal subarachnoid spaces, whereas apparent diffusivity was low there in patients with CoHy. Conclusion: DWI opens a feasible approach to study CSF motion in the neurocranium. Restricted arterial pulsations seem to be involved in CoHy.

  9. Elevated leukocyte count in cerebrospinal fluid of patients with chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Lucke, Ilse M; Peric, Stojan; van Lieverloo, Gwen G A; Wieske, Luuk; Verhamme, Camiel; van Schaik, Ivo N; Basta, Ivana; Eftimov, Filip

    2018-01-17

    Cerebrospinal fluid (CSF) examination is often part of the diagnostic work-up of a patient suspected of having chronic inflammatory demyelinating polyneuropathy (CIDP). According to the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria, an elevated protein level without pleocytosis (leukocytes leukocytes are compatible with the diagnosis CIDP and how extensive the diagnostic work-up should be in patients with a demyelinating neuropathy and pleocytosis. We performed a retrospective study at two tertiary neuromuscular referral clinics and identified 14 out of 273 (6%) patients with CIDP with elevated CSF leukocytes (≥10 cells/µl). All these patients met the EFNS/PNS criteria for definite or probable CIDP. Eight patients (57%) presented with a subacute onset and four patients with an antecedent infection. Most patients responded well to therapy, and eight patients are currently in remission. In four patients, lumbar puncture was repeated. A spontaneous decrease in leukocytes before start of treatment was found in three patients. Our data indicate that a mild to moderate pleocytosis in CSF does not exclude the diagnosis of CIDP, especially in patients with a subacute onset of disease. © 2018 Peripheral Nerve Society.

  10. Longitudinal Analysis of Novel Alzheimer’s Disease Proteomic Cerebrospinal Fluid Biomarkers During Intravenous Immunoglobulin Therapy

    Science.gov (United States)

    Shayan, Gilda; Adamiak, Basia; Relkin, Norman R.; Lee, Kelvin H.

    2018-01-01

    Intravenous immunoglobulin (IVIg) therapy has shown promising results in treating Alzheimer’s disease (AD). In this study, a Random Forest classification model was used to identify possible effects of IVIg on a group of eight subjects who underwent immunotherapy. Cerebrospinal fluid (CSF) samples from eight AD subjects who underwent IVIg therapy were collected before the therapy, after six months of therapy, and after a three-month drug washout period. Samples were analyzed using two-dimensional gel electrophoresis and further studied using a Random Forest classification model to identify effects of IVIg on a panel of 23 putative diagnostic AD biomarkers previously identified. Six of the eight subjects showed improvements with respect to the 23 AD diagnostic biomarkers after six months of therapy compared to the samples taken at the outset of the trial. All subjects reverted back to baseline during drug washout. These results are also consistent with clinical observations. The observed improvements in subjects during six months of IVIg therapy and the reversion back to baseline during drug washout provides preliminary evidence regarding the potential use of IVIg as an AD immunotherapy. PMID:22806462

  11. Detection of oligoclonal immunoglobulins in cerebrospinal fluid by an immunofixation-peroxidase method.

    Science.gov (United States)

    Richard, Sophie; Miossec, Véronique; Moreau, Jean-François; Taupin, Jean-Luc

    2002-01-01

    The detection of intrathecal synthesis of immunoglobulins is used in the diagnosis of multiple sclerosis (MS). We tested the semiautomated immunofixation-peroxidase (IFPOD) technique, which uses high-resolution agarose gel electrophoresis (HRAGE) directly followed by immunofixation with a peroxidase-labeled anti-IgG antiserum to detect oligoclonal immunoglobulins in cerebrospinal fluid (CSF). We analyzed 230 consecutive matched serum/CSF pairs that arrived in the laboratory over a 6-month period with both IFPOD and our routine techniques, immunofixation electrophoresis (IFE) and HRAGE. For IFPOD, CSF samples were not concentrated before testing. Among the 230 samples were 12 clinically definite MS, 33 clinically probable, and 20 clinically possible MS samples. IFPOD and HRAGE + IFE each detected oligoclonal IgG in CSF in 10, 16, and 7 cases of these respective groups. For clinically definite MS, sensitivity and specificity (95% confidence intervals) were, respectively, 83% (51-97%) and 79% (73-84%). The IFPOD technique performs comparably to other analytical methods, without the requirement for sample concentration, and may represent an attractive alternative in testing for intrathecal immunoglobulin synthesis.

  12. Genome-wide quantitative trait loci mapping of the human cerebrospinal fluid proteome.

    Science.gov (United States)

    Sasayama, Daimei; Hattori, Kotaro; Ogawa, Shintaro; Yokota, Yuuki; Matsumura, Ryo; Teraishi, Toshiya; Hori, Hiroaki; Ota, Miho; Yoshida, Sumiko; Kunugi, Hiroshi

    2017-01-01

    Cerebrospinal fluid (CSF) is virtually the only one accessible source of proteins derived from the central nervous system (CNS) of living humans and possibly reflects the pathophysiology of a variety of neuropsychiatric diseases. However, little is known regarding the genetic basis of variation in protein levels of human CSF. We examined CSF levels of 1,126 proteins in 133 subjects and performed a genome-wide association analysis of 514,227 single nucleotide polymorphisms (SNPs) to detect protein quantitative trait loci (pQTLs). To be conservative, Spearman's correlation was used to identify an association between genotypes of SNPs and protein levels. A total of 421 cis and 25 trans SNP-protein pairs were significantly correlated at a false discovery rate (FDR) of less than 0.01 (nominal P genome-wide association studies. The present findings suggest that genetic variations play an important role in the regulation of protein expression in the CNS. The obtained database may serve as a valuable resource to understand the genetic bases for CNS protein expression pattern in humans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients

    Science.gov (United States)

    Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

    2016-01-01

    The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrPSc) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly. PMID:27852982

  14. Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical Naturally Occurring Scrapie.

    Science.gov (United States)

    Llorens, Franc; Barrio, Tomás; Correia, Ângela; Villar-Piqué, Anna; Thüne, Katrin; Lange, Peter; Badiola, Juan José; Schmitz, Matthias; Lachmann, Ingolf; Bolea, Rosa; Zerr, Inga

    2018-03-23

    The analysis of the cerebrospinal fluid (CSF) biomarkers in patients with suspected prion diseases became a useful tool in diagnostic routine. Prion diseases can only be identified at clinical stages when the disease already spread throughout the brain and massive neuronal damage occurs. Consequently, the accuracy of CSF tests detecting non-symptomatic patients is unknown. Here, we aimed to investigate the usefulness of CSF-based diagnostic tests in pre-clinical and clinical naturally occurring scrapie. While decreased total prion protein (PrP) levels and positive PrP seeding activity were already detectable at pre-symptomatic stages, the surrogate markers of neuronal damage total tau (tau) and 14-3-3 proteins were exclusively increased at clinical stages. The present findings confirm that alterations in PrP levels and conformation are primary events in the pathology of prion diseases preceding neuronal damage. Our work also supports the potential use of these tests in the screening of pre-symptomatic scrapie and human prion disease cases.

  15. Possible role of the cavernous sinus veins in cerebrospinal fluid absorption

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    Koh Lena

    2007-04-01

    Full Text Available Abstract The purpose of this investigation was to enhance our understanding of cerebrospinal fluid (CSF absorption pathways. To achieve this, Microfil (a coloured silastic material was infused into the subarachnoid space (cisterna magna of sheep post mortem, and the relevant tissues examined macroscopically and microscopically. The Microfil was taken up by an extensive network of extracranial lymphatic vessels in the olfactory turbinates. In addition however, Microfil also passed consistently through the dura at the base of the brain. Microfil was noted in the spaces surrounding the venous network that comprises the cavernous sinus, in the adventitia of the internal carotid arteries and adjacent to the pituitary gland. Additionally, Microfil was observed within the endoneurial spaces of the trigeminal nerve and in lymphatic vessels emerging from the epineurium of the nerve. These results suggest several unconventional pathways by which CSF may be removed from the subarachnoid space. The movement of CSF to locations external to the cranium via these routes may lead to its absorption into veins and lymphatics outside of the skull. The physiological importance of these pathways requires further investigation.

  16. Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

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    Ehling Rainer

    2011-10-01

    Full Text Available Abstract Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF of acute and chronic central (CNS and peripheral nervous system (PNS diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS, acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM and PNS (Guillain-Barré syndrome; GBS, as well as in non-inflammatory neurological controls (OND in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.

  17. Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers.

    Science.gov (United States)

    Handels, Ron L H; Vos, Stephanie J B; Kramberger, Milica G; Jelic, Vesna; Blennow, Kaj; van Buchem, Mark; van der Flier, Wiesje; Freund-Levi, Yvonne; Hampel, Harald; Olde Rikkert, Marcel; Oleksik, Ania; Pirtosek, Zvezdan; Scheltens, Philip; Soininen, Hilkka; Teunissen, Charlotte; Tsolaki, Magda; Wallin, Asa K; Winblad, Bengt; Verhey, Frans R J; Visser, Pieter Jelle

    2017-08-01

    We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia. The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers. Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up. An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Phi, Ji Hoon; Choi, Seung Ah; Lim, Sang-Hee; Lee, Joongyub; Wang, Kyu-Chang; Park, Sung-Hye; Kim, Seung-Ki

    2013-01-01

    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

  19. Proteomic analysis of cerebrospinal fluid for relapsing-remitting multiple sclerosis and clinically isolated syndrome.

    Science.gov (United States)

    Pavelek, Zbyšek; Vyšata, Oldřich; Tambor, Vojtěch; Pimková, Kristýna; Vu, Dai Long; Kuča, Kamil; Šťourač, Pavel; Vališ, Martin

    2016-07-01

    Early diagnosis and treatment of multiple sclerosis (MS) in the initial stages of the disease can significantly retard its progression. The aim of the present study was to identify changes in the cerebrospinal fluid proteome in patients with relapsing-remitting MS and clinically isolated MS syndrome who are at high risk of developing MS (case group) compared to healthy population (control) in order to identify potential new markers, which could ultimately aid in early diagnosis of MS. The protein concentrations of each of the 11 case and 15 control samples were determined using a bicinchoninic acid assay. Nanoscale liquid chromatography coupled with tandem mass spectrometry was used for protein identification. Proteomics data were processed using the Perseus software suite and R. The results were filtered using the Benjamini-Hochberg procedure for the false discovery rate (FDR) correction (FDR<0.05). The results showed that, 26 proteins were significantly dysregulated in case samples compared to the controls. Nine proteins were found to be significantly less abundant in case samples, while the abundance of 17 proteins was significantly increased in case samples compared to controls. Three of the proteins were previously linked to RR MS, including immunoglobulin (Ig) γ-1 chain C region, Ig heavy chain V-III region BRO and Ig κ chain C region. Three proteins that were uniquely expressed in patients with RR MS were identified and these proteins may serve as prognostic biomarkers for identifying patients with a high risk of developing RR MS.

  20. Steady-streaming effects on the motion of the cerebrospinal fluid (CSF) in the spinal canal

    Science.gov (United States)

    Lawrence, Jenna; Coenen, Wilfried; Sanchez, Antonio; Lasheras, Juan

    2017-11-01

    With each heart beat the oscillatory blood supply to the rigid cranial vault produces a time-periodic variation of the intracranial pressure that drives the cerebrospinal fluid (CSF) periodically in and out of the compliant spinal canal. We have recently conducted an analysis of this flow-structure interaction problem taking advantage of the small compliance of the dura membrane bounding externally the CSF and of the disparity of length scales associated with the geometry of the subarachnoid space. We have shown in an idealized geometry that the steady-streaming motion associated with this periodic flow, resulting from the nonlinear cumulative effects of convective acceleration, causes a bulk recirculation of CSF inside the spinal canal, which has been observed in many radiological studies. We extend here our study to investigate the possible contribution arising from the flow around the nerve roots protruding from the spinal cord, an effect that was neglected in our previous work. For this purpose, we consider the oscillatory motion around a cylindrical post confined between two parallel plates. For large values of the relevant Strouhal number we find at leading order a harmonic Stokes flow, whereas steady-streaming effects enter in the first-order corrections, which are computed for realistic values of the Womersley number and of the cylinder height-to-radius ratio.

  1. Effects of age and glucose levels on lactate levels in cerebrospinal fluid examination of neurodegenerative diseases.

    Science.gov (United States)

    Nakano, Fumihito; Sakushima, Ken; Umeki, Reona; Yabe, Ichiro; Endoh, Akira; Sasaki, Hidenao

    2017-07-15

    Despite recent studies examining the association between neurodegenerative diseases and mitochondrial dysfunction, there are not sufficient data on factors that influence cerebrospinal fluid (CSF) lactate levels. Thus, we investigated factors that affect CSF lactate levels in neurodegenerative diseases. We extracted laboratory findings, including CSF lactate, glucose, and protein levels, and demographic and background information, including age and gender, from the electronic medical records of patients with neurodegenerative diseases in order to explore factors that have an impact CSF lactate levels. These patients had been admitted to our department and underwent a CSF examination between April 2007 and March 2015. Data from 83 patients (average age 64.5years; 45 males and 38 females) were analyzed. The patients' diagnoses included amyotrophic lateral sclerosis, multiple system atrophy, spinocerebellar degeneration, corticobasal syndrome, Parkinson's disease, and Huntington's disease. CSF lactate levels were higher in patients with a neurodegenerative disease who were aged 65years and older relative to those who were aged under 65years (pglucose levels showed a moderate positive correlation (r=0.487). Age and CSF glucose levels influenced CSF lactate levels even after adjusting for gender, age, CSF protein levels, and CSF glucose levels. When investigating CSF lactate levels in neurodegenerative diseases, it is necessary to consider patients' age and CSF glucose levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The circulation of the cerebrospinal fluid (CSF) in the spinal canal

    Science.gov (United States)

    Sanchez, Antonio L.; Martinez-Bazan, Carlos; Lasheras, Juan C.

    2016-11-01

    Cerebrospinal Fluid (CSF) is secreted in the choroid plexus in the lateral sinuses of the brain and fills the subarachnoid space bathing the external surfaces of the brain and the spinal canal. Absence of CSF circulation has been shown to impede its physiological function that includes, among others, supplying nutrients to neuronal and glial cells and removing the waste products of cellular metabolism. Radionuclide scanning images published by Di Chiro in 1964 showed upward migration of particle tracers from the lumbar region of the spinal canal, thereby suggesting the presence of an active bulk circulation responsible for bringing fresh CSF into the spinal canal and returning a portion of it to the cranial vault. However, the existence of this slow moving bulk circulation in the spinal canal has been a subject of dispute for the last 50 years. To date, there has been no physical explanation for the mechanism responsible for the establishment of such a bulk motion. We present a perturbation analysis of the flow in an idealized model of the spinal canal and show how steady streaming could be responsible for the establishment of such a circulation. The results of this analysis are compared to flow measurements conducted on in-vitro models of the spinal canal of adult humans.

  3. The effect of whole body position on lumbar cerebrospinal fluid opening pressure

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    Udommongkol Chesda

    2008-07-01

    Full Text Available Abstract We compared cerebrospinal fluid (CSF opening pressure measurements in the lumbar subarachnoid space between the flexed position (F-OP and relaxed position (R-OP in recumbent patients. We devised an equation for using F-OP to determine the existence of raised intracranial pressure (ICP. Patients (n = 83 underwent lumbar puncture while in the flexed lateral decubitus position and then were moved to the relaxed position. F-OP and R-OP were measured with a water manometer. R-OP > 180 mmH2O plus relevant clinical signs were taken as indicators of raised intracranial pressure. Mean pressures for F-OP and R-OP were 178.54 and 160.52 mmH2O respectively, p 180, raised ICP could be significantly over diagnosed. The authors recommend an equation [R-OP(calculated, mmH2O = 0.885 × F-OP(measured, mmH2O] or using 200 mmH2O as the threshold for increased ICP with flexed posture.

  4. Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development.

    Science.gov (United States)

    Alonso, M I; Martín, C; Carnicero, E; Bueno, D; Gato, A

    2011-07-01

    Embryonic-cerebrospinal fluid (E-CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E-CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E-CSF contains all-trans-retinol and retinol-binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic-rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E-CSF helps to control RA synthesis in the IsO by means of the RBP and all-trans-retinol it contains; (2) E-CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E-CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. Copyright © 2011 Wiley-Liss, Inc.

  5. Red blood cells in cerebrospinal fluid as possible inhibitory factor for enterovirus RT-PCR

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    Sérgio Monteiro de Almeida

    Full Text Available ABSTRACT The presence of hemoglobin in samples are considered an important inhibitory factor for polymerase chain reaction (PCR. The aim of this study was to examine the influence of red blood cells (RBCs in cerebrospinal fluid (CSF as an inhibitory factor to reverse transcription polymerase chain reaction (RT-PCR for enteroviruses (EV. Forty-four CSF samples from patients showing characteristics of viral meningitis were assessed for EV by RT-PCR. Viral RNA extracted with guanidine isothyocianate buffer and virus detection was performed by in-house nested PCR. Positivity for EV RT-PCR was higher in CSF samples without RBCs than in samples with RBCs: 13(26% and 36(9.2%, p = 0.001. In the group with positive EV RT-PCR, the mean + SD CSF RBC was 37 ± 183 cell/mm3; the group with negative results had 580 + 2,890 cell/mm3 (p = 0.007. The acceptable upper limit for CSF RBCs that could not influence RT-PCR was 108 cells/mm3. CSF samples with negative results for EV RT-PCR have more erythrocytes.

  6. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

    Directory of Open Access Journals (Sweden)

    Alexandr Krasota

    2016-01-01

    Full Text Available Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1% patients compared with 75 (47.2%, 53 (33.3% and 31 (19.5% achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14, E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71 in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

  7. Higher level of NT-proCNP in cerebrospinal fluid of patients with meningitis.

    Science.gov (United States)

    Tomasiuk, Ryszard; Lipowski, Dariusz; Szlufik, Stanislaw; Peplinska, Krystyna; Mikaszewska-Sokolewicz, Malgorzata

    2016-02-12

    Aminoterminal pro-C type natriuretic peptide (NT-proCNP) as an active form of CNP, has been recently proven to be a potential marker of sepsis and to be linked to inflammatory diseases. So far, there are no studies describing the level of NT-proCNP in meningitis. The purpose of this study was to evaluate the diagnostic value of NT-proCNP in cerebrospinal fluid (CSF) in patients with meningitis and to compare it with the serum level of CRP and procalcitonin (PCT) in this group of patients. The results were compared to serum levels of CRP, PCT and CSF levels of cytosis, protein and lactate. NT-proCNP levels were statistically significant between the control group and the meningitis groups (p=0.02; R=0.3). We also noted a correlation between the level of NT-proCNP in the CSF of all of the study groups (controls and meningitis patients) and the CSF levels of cytosis (p0.05; R=0.11). These results suggest that NT-proCNP could be a potential marker of meningitis, but it cannot be used to distinguish between the types of meningitis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Automatic cerebrospinal fluid segmentation in non-contrast CT images using a 3D convolutional network

    Science.gov (United States)

    Patel, Ajay; van de Leemput, Sil C.; Prokop, Mathias; van Ginneken, Bram; Manniesing, Rashindra

    2017-03-01

    Segmentation of anatomical structures is fundamental in the development of computer aided diagnosis systems for cerebral pathologies. Manual annotations are laborious, time consuming and subject to human error and observer variability. Accurate quantification of cerebrospinal fluid (CSF) can be employed as a morphometric measure for diagnosis and patient outcome prediction. However, segmenting CSF in non-contrast CT images is complicated by low soft tissue contrast and image noise. In this paper we propose a state-of-the-art method using a multi-scale three-dimensional (3D) fully convolutional neural network (CNN) to automatically segment all CSF within the cranial cavity. The method is trained on a small dataset comprised of four manually annotated cerebral CT images. Quantitative evaluation of a separate test dataset of four images shows a mean Dice similarity coefficient of 0.87 +/- 0.01 and mean absolute volume difference of 4.77 +/- 2.70 %. The average prediction time was 68 seconds. Our method allows for fast and fully automated 3D segmentation of cerebral CSF in non-contrast CT, and shows promising results despite a limited amount of training data.

  9. Systemic pharmacokinetics and cerebrospinal fluid uptake of intravenous ceftriaxone in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhao, Yanli; Cudkowicz, Merit E; Shefner, Jeremy M; Krivickas, Lisa; David, William S; Vriesendorp, Francine; Pestronk, Alan; Caress, James B; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Harmatz, Jerold S; Schoenfeld, David; Greenblatt, David J

    2014-10-01

    The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS). The pharmacokinetics (PK) of ceftriaxone in plasma and cerebrospinal fluid (CSF) were investigated in 66 participants in a previously reported clinical trial. Their mean age was 51 years, and 65% were male. Participants were randomly assigned to 1 of 3 treatment groups receiving intravenous infusions (mean duration: 25 minutes) every 12 hours of either: placebo and placebo; 2 g ceftriaxone and placebo; or 2 g ceftriaxone twice. Mean steady-state plasma PK variables were: volume of distribution, 14 L (0.17 L/kg); elimination half-life, 8-9 h; total clearance, 17-21 mL/min (0.22-0.25 mL/min/kg). Values were not different between dosage groups. CSF PK analysis, determined through sparse CSF sampling, indicated apparent entry and elimination half-life values of 1.0 and 34 hours, respectively. With both dosage regimens, CSF concentrations were maintained above the target threshold of 1.0 µM (0.55 µg/mL) as determined from in vitro models. The plasma and CSF PK profiles of ceftriaxone were used as a basis for planning the Phase 3 clinical trial of ceftriaxone in ALS. © 2014, The American College of Clinical Pharmacology.

  10. Cerebrospinal Fluid Cathelicidin Correlates With the Bacterial Load and Outcomes in Childhood Bacterial Meningitis.

    Science.gov (United States)

    Savonius, Okko; Helve, Otto; Roine, Irmeli; Andersson, Sture; Saukkoriipi, Annika; González Mata, Antonio; Peltola, Heikki; Pelkonen, Tuula

    2018-02-01

    Large cerebrospinal fluid (CSF) bacterial load in bacterial meningitis (BM) relates to poor outcome. However, the antimicrobial peptide cathelicidin seems important to host defense. We studied how cathelicidin concentrations and bacterial load in CSF relate in childhood BM and to what extent they may predict the disease outcome. The patient data originated from a large prospective clinical trial in Latin America in 1996-2003 in which the CSF samples were collected on admission (CSF1) and 12-24 hours later (CSF2). The cathelicidin concentrations were measured by enzyme-linked immunosorbent assay and the CSF bacterial load by real-time polymerase chain reaction. This analysis comprised 76 children with meningitis caused by Haemophilus influenzae type b (n = 44), Streptococcus pneumoniae (n = 28) or Neisseria meningitidis (n = 4). The cathelicidin concentration correlated with the bacterial genome count in both samples (CSF1: ρ = 0.531, P < 0.001; CSF2: ρ = 0.553, P < 0.001). A high CSF1 ratio of cathelicidin to the bacterial genome count was associated with fewer audiologic sequelae (odds ratio: 0.11, 95% confidence interval: 0.02-0.61, P = 0.01) and more favorable neurologic outcomes (odds ratio: 3.95, 95% confidence interval: 1.22-12.8, P = 0.02), but not with better survival. In conclusion, CSF cathelicidin and the bacterial load were closely related in childhood BM. A high initial cathelicidin-to-bacterial genome count ratio predicted better outcomes in survivors.

  11. Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children.

    Science.gov (United States)

    Njunge, James M; Oyaro, Ian N; Kibinge, Nelson K; Rono, Martin K; Kariuki, Symon M; Newton, Charles R; Berkley, James A; Gitau, Evelyn N

    2017-01-01

    Background . Few hospitals in high malaria endemic countries in Africa have the diagnostic capacity for clinically distinguishing acute bacterial meningitis (ABM) from cerebral malaria (CM). As a result, empirical use of antibiotics is necessary. A biochemical marker of ABM would facilitate precise clinical diagnosis and management of these infections and enable rational use of antibiotics. Methods. We used label-free protein quantification by mass spectrometry to identify cerebrospinal fluid (CSF) markers that distinguish ABM (n=37) from CM (n=22) in Kenyan children. Fold change (FC) and false discovery rates (FDR) were used to identify differentially expressed proteins. Subsequently, potential biomarkers were assessed for their ability to discriminate between ABM and CM using receiver operating characteristic (ROC) curves. Results. The host CSF proteome response to ABM ( Haemophilus influenza and Streptococcus pneumoniae ) is significantly different to CM. Fifty two proteins were differentially expressed (FDR<0.01, Log FC≥2), of which 83% (43/52) were upregulated in ABM compared to CM. Myeloperoxidase and lactotransferrin were present in 37 (100%) and 36 (97%) of ABM cases, respectively, but absent in CM (n=22). Area under the ROC curve (AUC), sensitivity, and specificity were assessed for myeloperoxidase (1, 1, and 1; 95% CI, 1-1) and lactotransferrin (0.98, 0.97, and 1; 95% CI, 0.96-1). Conclusion. Myeloperoxidase and lactotransferrin have a high potential to distinguish ABM from CM and thereby improve clinical management. Their validation requires a larger cohort of samples that includes other bacterial aetiologies of ABM.

  12. Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants.

    Science.gov (United States)

    Srinivasan, Lakshmi; Kilpatrick, Laurie; Shah, Samir S; Abbasi, Soraya; Harris, Mary C

    2016-10-01

    Bacterial meningitis poses diagnostic challenges in infants. Antibiotic pretreatment and low bacterial density diminish cerebrospinal fluid (CSF) culture yield, while laboratory parameters do not reliably identify bacterial meningitis. Pro and anti-inflammatory cytokines are elevated in bacterial meningitis and may be useful diagnostic adjuncts when CSF cultures are negative. In a prospective cohort study of infants, we used cytometric bead arrays to measure tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), IL-6, IL-8, IL-10, and IL-12 in CSF. Receiver operating characteristic (ROC) analyses and Principal component analysis (PCA) were used to determine cytokine combinations that identified bacterial meningitis. Six hundred and eighty four infants bacterial meningitis. IL-6 and IL-10 were the individual cytokines possessing greatest accuracy in diagnosis of culture proven bacterial meningitis (ROC analyses; area under the concentration-time curve (AUC) 0.91; 0.9103 respectively), and performed as well as, or better than combinations identified using ROC and PCA. CSF cytokines were highly correlated with each other and with CSF white blood cell count (WBC) counts in infants with meningitis. A subset of antibiotic pretreated culture-negative subjects demonstrated cytokine patterns similar to culture positive subjects. CSF cytokine levels may aid diagnosis of bacterial meningitis, and facilitate decision-making regarding treatment for culture negative meningitis.

  13. Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein.

    Science.gov (United States)

    Tan, Jintong; Kan, Juan; Qiu, Gang; Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

    2015-01-01

    Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1-4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis.

  14. Analysis of clinical outcomes in pediatric bacterial meningitis focusing on patients without cerebrospinal fluid pleocytosis.

    Science.gov (United States)

    Lin, Wen-Li; Chi, Hsin; Huang, Fu-Yuan; Huang, Daniel Tsung-Ning; Chiu, Nan-Chang

    2016-10-01

    Cerebrospinal fluid (CSF) cell count and biochemical examinations and cultures form the basis for the diagnosis of bacterial meningitis. However, some patients do not have typical findings and are at a higher risk of being missed or having delayed treatment. To better understand the correlation between CSF results and outcomes, we evaluated CSF data focusing on the patients with atypical findings. This study enrolled CSF culture-proven bacterial meningitis patients aged from 1 month to 18 years in a medical center. The patients were divided into "normal" and "abnormal" groups for each laboratory result and in combination. The correlations between the laboratory results and the outcomes were analyzed. A total of 175 children with confirmed bacterial meningitis were enrolled. In CSF examinations, 16.2% of patients had normal white blood cell counts, 29.5% had normal glucose levels, 24.5% had normal protein levels, 10.2% had normal results in two items, and 8.6% had normal results in all three items. In logistic regression analysis, a normal CSF leukocyte count and increased CSF protein level were related to poor outcomes. Patients with meningitis caused by Streptococcus pneumoniae and hyponatremia were at a higher risk of mortality and the development of sequelae. In children with bacterial meningitis, nontypical CSF findings and, in particular, normal CSF leukocyte count and increased protein level may indicate a worse prognosis. Copyright © 2014. Published by Elsevier B.V.

  15. Elevation of tau protein levels in the cerebrospinal fluid of children with West syndrome.

    Science.gov (United States)

    Inoue, Hirofumi; Matsushige, Takeshi; Hasegawa, Shunji; Abe, Arisa; Iida, Yasunori; Inoue, Teruaki; Ichiyama, Takashi

    2012-11-01

    West syndrome is an epileptic encephalopathy with a poor developmental outcome. Tau protein levels in the cerebrospinal fluid (CSF) are reported to be markers of axonal damage and neurodegeneration. This study aimed to investigate axonal damage and the effects of adrenocorticotropic hormone (ACTH) therapy on axons in West syndrome, as measured by tau protein levels in CSF. Tau protein levels in CSF before and after ACTH therapy were determined by an enzyme-linked immunosorbent assay in 26 children with West syndrome. Of these 26 children, 18 were symptomatic, and 8 had a cryptogenic form of West syndrome. A group of 41 unaffected children was included in the study as a control group. The levels of tau protein in CSF were significantly higher in children with West syndrome than in the control group, and these levels remained high after ACTH therapy. ACTH therapy was effective for 20 of the 26 children with West syndrome, and their CSF tau protein levels were significantly higher after ACTH therapy than before therapy. Our results suggest that axonal damage occurs in West syndrome, as judged by tau protein levels in CSF. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. A Cerebrospinal Fluid Collection Study in Pediatric and Adult Patients With Hunter Syndrome

    Directory of Open Access Journals (Sweden)

    Christian J. Hendriksz MD

    2015-08-01

    Full Text Available Hunter syndrome (mucopolysaccharidosis II [MPS II] is characterized by lysosomal glycosaminoglycan (GAG accumulation. Although a majority of patients with MPS II experience neurocognitive involvement, few data are available on cerebrospinal fluid (CSF GAG levels in these patients. This study measured GAG levels in CSF collected from 9 patients with MPS II, including 4 adults (aged ≥18 years with normal cognition, and 5 children, 3 of them with cognitive impairment. The CSF total GAG levels were generally higher in the 3 patients with cognitive impairment (range 842.9-2360.9 ng/mL versus those with normal cognitive status (range 356.8-1181.1 ng/mL. Heparan sulfate levels, as measured by mass spectrometry, generally followed a similar pattern, with patients with the severe phenotype having the highest values. These data, limited by small sample size, suggest CSF GAG levels and heparan sulfate levels may be higher in patients with cognitive impairment versus patients with cognitively intact MPS II.

  17. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    Science.gov (United States)

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-γ concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-γ may be associated with EV71-induced neuropathology. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  18. Plasma and cerebrospinal fluid pharmacokinetics of the histone deacetylase inhibitor, belinostat (PXD101), in non-human primates

    DEFF Research Database (Denmark)

    Warren, K.E.; McCully, C.; Dvinge, H.

    2008-01-01

    is a novel, potent, pan-HDAC inhibitor with antiproliferative activity on a wide variety of tumor cell lines. We studied the cerebrospinal fluid (CSF) penetration of intravenous (IV) belinostat in a non-human primate model as a surrogate for blood:brain barrier penetration. DESIGN: Five adult rhesus monkeys....... CSF drug exposure was drug exposure and drug exposure. CONCLUSION: IV belinostat is rapidly cleared from plasma and has limited penetration into the CSF Udgivelsesdato: 2008/8...

  19. Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

    Science.gov (United States)

    Zhang, Linda W.; Warrington, Junie P.

    2016-01-01

    Magnesium sulfate (MgSO4) is the most widely used therapy in the clinic to prevent the progression of preeclampsia, a hypertensive disorder of pregnancy, to eclampsia. Eclampsia, manifested as unexplained seizures and/or coma during pregnancy or postpartum, accounts for ~13% of maternal deaths worldwide. While MgSO4 continues to be used in the clinic, the mechanisms by which it exerts its protective actions are not well understood. In this study, we tested the hypothesis that MgSO4 protects against placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines. To test this hypothesis, MgSO4 was administered via mini-osmotic pump (60 mg/day, i.p.) to pregnant and placental ischemic rats, induced by mechanical reduction of uterine perfusion pressure, from gestational day 14–19. This treatment regimen of MgSO4 led to therapeutic level of 2.8 ± 0.6 mmol/L Mg in plasma. MgSO4 had no effect on improving placental ischemia-induced changes in mean arterial pressure, number of live fetuses, or fetal and placental weight. Placental ischemia increased, while MgSO4 prevented the increase in water content in the anterior cerebrum. Cytokine and chemokine levels were measured in the cerebrospinal fluid using a multi-plex assay. Results demonstrate that cerebrospinal fluid, obtained via the cisterna magna, had reduced protein, albumin, interleukin (IL)-17A, IL-18, IL-2, eotaxin, fractalkine, interferon gamma, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-2 following MgSO4 treatment. These data support the hypothesis that MgSO4 offers neuroprotection by preventing placental ischemia-induced cerebral edema and reducing levels of cytokines/chemokines in the cerebrospinal fluid. PMID:28008305

  20. Levels of Matrix Metalloproteinase-9 within Cerebrospinal Fluid in a Rabbit Model of Coccidioidal Meningitis and Vasculitis

    OpenAIRE

    Williams, Paul L.; Leib, Stephen L.; Kamberi, Perparim; Leppert, David; Sobel, Raymond A.; Bifrare, Yoeng-Delphine; Clemons, Karl V.; Stevens, David A.

    2017-01-01

    Matrix metalloproteinase (MMP)-9 is produced by the central nervous system and inflammatory cells in a variety of inflammatory conditions in both animals and humans. MMP-9 promotes inflammation, breakdown of the blood-brain barrier, and vasculitis. Because vasculitis is seen frequently in patients with coccidioidal meningitis (CM), this study evaluated the presence of MMP-9 within the cerebrospinal fluid (CSF) of rabbits infected intracisternally with Coccidioides immitis arthroconidia. Infec...

  1. Cerebrospinal fluid analysis in infectious diseases of the nervous system: when to ask, what to ask, what to expect

    Directory of Open Access Journals (Sweden)

    Luis dos Ramos Machado

    2013-09-01

    Full Text Available Cerebrospinal fluid (CSF analysis very frequently makes the difference to the diagnosis, not only in relation to infections but also in other diseases of the nervous system such as inflammatory, demyelinating, neoplastic and degenerative diseases. The authors review some practical and important features of CSF analysis in infectious diseases of the nervous system, with regard to acute bacterial meningitis, herpetic meningoencephalitis, neurotuberculosis, neurocryptococcosis, neurocysticercosis and neurosyphilis.

  2. Efflux of Iron from the Cerebrospinal Fluid to the Blood at the Blood-CSF Barrier: Effect of Manganese Exposure

    OpenAIRE

    Wang, Xueqian; Li, G. Jane; Zheng, Wei

    2008-01-01

    The blood-cerebrospinal fluid (CSF) barrier (BCB) resides within the choroid plexus, with the apical side facing the CSF and the basolateral side towards the blood. Previous studies demonstrate that manganese (Mn) exposure in rats disrupts iron (Fe) homeostasis in the blood and CSF. The present study used a primary culture of rat choroidal epithelial cells grown in the two-chamber Transwell system to investigate the transepithelial transport of Fe across the BCB. Free, unbound Fe as [59Fe] wa...

  3. Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport.

    Science.gov (United States)

    Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

    2017-05-15

    The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. Copyright © 2017. Published by Elsevier Inc.

  4. Osmolality of Cerebrospinal Fluid from Patients with Idiopathic Intracranial Hypertension (IIH.

    Directory of Open Access Journals (Sweden)

    Elisabeth A Wibroe

    Full Text Available Idiopathic intracranial hypertension (IIH is a disorder of increased intracranial fluid pressure (ICP of unknown etiology. This study aims to investigate osmolality of cerebrospinal fluid (CSF from patients with IIH.We prospectively collected CSF from individuals referred on suspicion of IIH from 2011-2013. Subjects included as patients fulfilled Friedman and Jacobson's diagnostic criteria for IIH. Individuals in whom intracranial hypertension was refuted were included as controls. Lumbar puncture with ICP measurement was performed at inclusion and repeated for patients after three months of treatment. Osmolality was measured with a Vapor Pressure Osmometer.We collected 90 CSF samples from 38 newly diagnosed patients and 28 controls. At baseline 27 IIH-samples and at 3 months follow-up 35 IIH-samples were collected from patients. We found no significant differences in osmolality between 1 patients at baseline and controls (p = 0. 86, 2 patients at baseline and after 3 months treatment (p = 0.97, and 3 patients with normalized pressure after 3 months and their baseline values (p = 0.79. Osmolality in individuals with normal ICP from 6-25 cmH2O (n = 41 did not differ significantly from patients with moderately elevated ICP from 26-45 cmH2O (n = 21 (p = 0.86 and patients with high ICP from 46-70 cmH2O (n = 4 (p = 0.32, respectively. There was no correlation between osmolality and ICP, BMI, age and body height, respectively. Mean CSF osmolality was 270 mmol/kg (± 1 SE, 95% confidence interval 267-272 for both patients and controls.CSF osmolality was normal in patients with IIH, and there was no relation to treatment, ICP, BMI, age and body height. Mean CSF osmolality was 270 mmol/kg and constitutes a reference for future studies. Changes in CSF osmolality are not responsible for development of IIH. Other underlying pathophysiological mechanisms must be searched.

  5. Lead poisoning due to gunshot bullet in contact with cerebrospinal fluid: case report

    Directory of Open Access Journals (Sweden)

    Paulo Roberto de Madureira

    Full Text Available CONTEXT: Lead poisoning due to retained gunshot bullets is a well-known clinical problem that is fairly frequently described in the literature. The risk factors for this occurrence relate mainly to whether the lead bullet is in contact with the joint fluid or cerebrospinal fluid (CSF. The treatment for these cases entails chelation therapy while symptoms are shown and definitive surgical removal of the bullet as a potential source of lead. The aim of this paper is to describe a clinical case of lead poisoning due to a retained gunshot bullet in contact with CSF. CASE REPORT: A 42-year-old male was hit by gunshot bullets during a holdup, and one of them was retained in the spinal cord. Six years later, he developed intense low back pain and underwent laminectomy. Nine years later, he then underwent arthrodesis on L5-S1, but he developed intense abdominal pain after the surgical procedure. For five years, he was treated with calcium versenate in five-day cycles, with a good response. The chelation therapy cycles showed great efficacy during symptomatic periods, thus reducing the symptoms and signs of poisoning and promoting great amounts of lead excretion, thereby reducing the total lead burden responsible for the symptoms. Fortunately, over the last four years, the symptoms have improved and the urine levels of aminolevulinic acid (ALA have declined, to reach complete normalization. This shows that a healing process is probably taking place on the spinal wound, thereby isolating the bullet fragments from CSF contact.

  6. MicroRNAs in Cerebrospinal Fluid as Potential Biomarkers for Parkinson's Disease and Multiple System Atrophy.

    Science.gov (United States)

    Marques, Tainá M; Kuiperij, H Bea; Bruinsma, Ilona B; van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Bloem, Bas R; Verbeek, Marcel M

    2017-12-01

    Parkinson's disease (PD) and multiple system atrophy (MSA) are both part of the spectrum of neurodegenerative movement disorders and α-synucleinopathies with overlap of symptoms especially at early stages of the disease but with distinct disease progression and responses to dopaminergic treatment. Therefore, having biomarkers that specifically classify patients, which could discriminate PD from MSA, would be very useful. MicroRNAs (miRNAs) regulate protein translation and are observed in biological fluids, including cerebrospinal fluid (CSF), and may therefore have potential as biomarkers of disease. The aim of our study was to determine if miRNAs in CSF could be used as biomarkers for either PD or MSA. Using quantitative PCR (qPCR), we evaluated expression levels of 10 miRNAs in CSF patient samples from PD (n = 28), MSA (n = 17), and non-neurological controls (n = 28). We identified two miRNAs (miR-24 and miR-205) that distinguished PD from controls and four miRNAs that differentiated MSA from controls (miR-19a, miR-19b, miR-24, and miR-34c). Combinations of miRNAs accurately discriminated either PD (area under the curve (AUC) = 0.96) or MSA (AUC = 0.86) from controls. In MSA, we also observed that miR-24 and miR-148b correlated with cerebellar ataxia symptoms, suggesting that these miRNAs are involved in cerebellar degeneration in MSA. Our findings support the potential of miRNA panels as biomarkers for movement disorders and may provide more insights into the pathological mechanisms related to these disorders.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Specific Anti Mumps Antibodies (IgG & IgM in Cerebrospinal Fluid of Mumps Meningoencephalitic Children

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    Noorbakhsh Samileh

    2009-10-01

    Full Text Available Mumps infection is endemic in Iran. Our objective was to evaluate the presence of anti mumps antibodies ( IgM & IgG in cerebrospinal fluid in mumps meningoencephalitic children. A prospective/cross-sectional study was performed in Tehran, Iran (2003 to 2004 and serum anti mumps antibodies (IgM were detected (quantitive; ELISA in meningoencephaltis patients. Specific anti mumps antibodies (IgM & IgG were detected in cerebrospinal fluids of mumps meningoencephalitis cases. 43 meningoencephalitic patients were tested (59.2% male and 40.8% female. The age of patients was 79.96 ± 4.7 month. 23 (78.7% cases had specific mumps IgM in serum. None of cases had IgM antibodies in CSF. Anti mumps IgG antibody was detected in CSF of 7.5% (2/23 cases. We detected lower than expected frequency of local immunity to mumps virus in CSF of our cases. For better serologic diagnosis we recommend more sensitive methods like virus detection (PCR or short-term culture of lymphocytes from cerebrospinal fluid in future studies.

  9. Concentration of Donepezil in the Cerebrospinal Fluid of AD Patients: Evaluation of Dosage Sufficiency in Standard Treatment Strategy.

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    Valis, Martin; Masopust, Jiri; Vysata, Oldrich; Hort, Jakub; Dolezal, Rafael; Tomek, Jiri; Misik, Jan; Kuca, Kamil; Karasova, Jana Zdarova

    2017-01-01

    Although some studies have described the pharmacokinetics and pharmacodynamics of donepezil in the peripheral compartment, studies focused on drug transport across the blood-brain barrier are still very rare. To our knowledge, the fluctuation in the cerebrospinal fluid concentration of donepezil after administration of the drug has not been described in the literature so far. We recruited 16 patients regularly taking a standard therapeutic dose of donepezil (10 mg per day). All patients (Caucasian race) were treated for at least three months with a stable dose of 10 mg per day prior to sample collection. Patients were divided into two groups depending on the time of plasma and cerebrospinal fluid sampling: 12 h (n = 9; 4 M/5F aged 78.68 ± 7.35 years) and 24 h (n = 7; 3 M/4F aged 77.14 ± 5.87 years) after donepezil administration. The cerebrospinal fluid sample was collected by standard lumbar puncture technique using a single-use traumatic needle. The samples were analysed on an Agilent 1260 Series liquid chromatograph comprising a degasser, a quaternary pump, a light-tight autosampler unit set, a thermostated column compartment, and a UV/VIS detector. Agilent ChemStation software, the statistical software Prism4, version 5.0 (GraphPad Software, USA), and IBM ® SPSS ® Statistics were used for the analysis of the results. The difference in plasma concentration of donepezil after 12 h (mean ± SEM; 39.99 ± 5.90 ng/ml) and after 24 h (29.38 ± 1.71 ng/ml) was nonsignificant. In contrast, the donepezil concentration in the cerebrospinal fluid was significantly higher in the 24-h interval (7.54 ± 0.55 ng/ml) compared with the 12-h interval (5.19 ± 0.83 ng/ml, which is ~70 % based on mean cerebrospinal fluid values). Based on these data, it is plausible to predict that donepezil might produce a stronger AChE inhibition in the brain at 24 h compared with 12 h following the administration. This information may help physicians

  10. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

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    Stopa Edward G

    2008-05-01

    Full Text Available Abstract This review integrates eight aspects of cerebrospinal fluid (CSF circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5, ion transporters (NaHCO3 cotransport, transport enzymes (isoforms of carbonic anhydrase, aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility, hydrodynamics (choroidal hypo- and hypersecretion and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor. In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF convection with both trophic

  11. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease.

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    Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

    2008-05-14

    This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory

  12. Líquido cefalorraqueano em 50 pacientes com AIDS Cerebrospinal fluid in 50 AIDS patients

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    S. L. Hinrichsen

    1996-06-01

    Full Text Available Foram estudados 50 pacientes com AIDS. Todos estes pacientes apresentavam anticorpos anti-HIV1 (ELISA e preenchiam os critérios de pontuação OPAS/Caracas de definição de casos de AIDS em adultos. A análise do liquido cefalorraqueano (LCR incluiu: pressão; citologia (número de células e aspectos citomorfológicos; proteína total e eletroforese; concentrações de glicose, cloretos e testes imunológicos para sífilis, toxoplasmose e infecções virais (citomegalovírus, varicela-zoster, Herpes simplex, e HI VI. Investigações bacteriológicas e micológicas (pesquisa direta e cultura, além de teste de aglutinação (látex para Cryptococcus foram também realizados. Os testes imunológicos usados foram fixação do complemento, imunofluorescência indireta, hemaglutinação passiva e/ou ELISA. Todos os LCR foram analisados no mesmo laboratório seguindo sempre a mesma metodologia. O LCR esteve alterado em 45 pacientes (90,0% dos 50 pacientes estudados. As principais alterações encontradas no LCR foram: aumento de gamaglobulina em 25 casos (55,5%; aumento da proteína total em 23 (51,1%; hipercitose em 22 (48,9% e diminuição dos cloretos em 18(40,0%. A detecção de anticorpos anti- HIV1 estiveram presentes em 42 pacientes (93,3%. Toxoplasmose isolada ou associada a outros agentes foi a infecção oportunista mais freqüente, detectada em 26 casos (57,7%. O LCR deverá ser sempre analisado em todos os pacientes com AIDS, com ou sem sintomas neurológicos.Fifty AIDS patients were studied. AH patients had anti-HIV antibodies (ELISA present and met OPAS/ Caracas punctuation criteria for AIDS cases in adults. Cerebrospinal fluid (CSF analysis included pressure, cytology (number and cytomorphological aspects, total protein and electrophoresis, glucose and chloride concentration. Bacteriological and mycological investigations were performed as well as agglutination tests for Cryptococcus. Complement fixation, indirect immunoflorescence

  13. Cerebrospinal fluid levels of Alzheimer's disease biomarkers in middle-aged patients with type 1 diabetes.

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    Ouwens, D Margriet; van Duinkerken, Eelco; Schoonenboom, S Niki M; Herzfeld de Wiza, Daniella; Klein, Martin; van Golen, Larissa; Pouwels, Petra J W; Barkhof, Frederik; Moll, Annette C; Snoek, Frank J; Teunissen, Charlotte E; Scheltens, Philip; Diamant, Michaela

    2014-10-01

    Type 1 diabetes is associated with moderate cognitive decline and cerebral alterations and may lead to an increased risk of dementia, including Alzheimer's disease. This study aimed to investigate the levels of risk markers for Alzheimer's disease in middle-aged patients with type 1 diabetes and controls, and their potential associations with cognitive and cerebral measures. Levels of β-amyloid (Aβ) 42, Tau, phosphorylated Tau (pTau), the soluble form of low-density lipoprotein receptor-related protein 1 (sLRP1) and macrophage colony-stimulating factor (MCSF) were quantified by ELISA in serum and cerebrospinal fluid (CSF) collected from 37 patients with type 1 diabetes and 15 controls. Associations between biomarkers and determinants of cognitive function and white matter integrity were assessed using hierarchical regression analysis controlling for age, HbA1c and estimated intelligence quotient (IQ). CSF levels of pTau, Aβ42 and LRP1 were higher in patients with type 1 diabetes than in controls (all p < 0.05). There was a trend towards increased Tau levels in patients with type 1 diabetes (p = 0.056), while CSF levels of MCSF were similar between patients with type 1 diabetes and controls. Regression analysis showed that elevated CSF sLRP1 levels were associated with better attention (β = 0.518; p = 0.002) and a better speed of information-processing (β = 0.368; p = 0.034), as well as increased integrity of the white matter of the right inferior fronto-occipital tract (β = 0.395; p = 0.022). Furthermore, elevated Tau levels were associated with decreased integrity of the white matter of right inferior fronto-occipital tract (β = -0.584; p = 0.002). CSF levels of biomarkers for Alzheimer's disease are altered in patients with type 1 diabetes compared with controls, but the observed profile does not match the profile characterising pre-Alzheimer's disease patients.

  14. Pulsatile flow of cerebrospinal fluid on magnetic resonance images and its relation to intracranial pressure

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    Ohara, Shigeki

    1988-01-01

    In a retrospective study of the magnetic resonance (MR) images of 289 neurosurgical patients, loss of signal intensity (the signal void phenomenon) of cerebrospinal fluid (CSF) in the mesencephalic aqueduct was observed in 77 patients. This signal void phenomenon (SVP) was seen most frequently in patients suffering from communicating hydrocephalus (12 of 14), less frequently in patients with supratentorial tumors (7 of 50), and not at all in patients with noncommunicating hydrocephalus (none of 9). Eight of 19 patients with infratentorial lesions who did not demonstrate the SVP preoperatively, developed it after suboccipital craniectomy. It is known that CSF in the cranial cavity flows toward the spinal CSF space in a to and fro manner in response to the pulsations of the brain. The velocity of this flow is faster in the narrower parts in the ventricular system such as the aqueduct, Monro's foramen and the fourth ventricle. The SVP reflects CSF pulsatile flow forced out of the intracranial space into the intraspinal space by the brain's pulsations. The SVP was observed frequently in the MR images of patients with communicating hydrocephalus who showed normal intracranial mean pressure (mICP) and normal pulse pressure (PP), whereas the SVP was observed rarely in patients with high mICP and high PP, such as those with a supratentorial tumor. The SVP may reflect the capacity of the craniospinal cavity to buffer pressure within it. It may be possible to differentiate normal from increased intracranial pressure by detection of the SVP in CSF in the ventricular system. (author)

  15. Cerebrospinal fluid adenosine deaminase activity: A complimentary tool in the early diagnosis of tuberculous meningitis

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    Taori Girdhar M

    2006-03-01

    Full Text Available Abstract Background Tuberculous meningitis (TBM is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB. The diagnosis of TBM is often difficult. A reliable, cost-effective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA activity in cerebrospinal fluid (CSF of TBM and non-TBM patients. Method ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. Results The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 ± 3.87 (2.99–26.94, mean ± SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 ± 2.14 (4.99–13.96 and from the non-infectious neurological disorders group, 2.71 ± 1.96 (0.00–7.68, P Conclusion This study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.

  16. Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid

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    Seow Hoon Saw

    2016-09-01

    Full Text Available Background Meningitis is a major cause of mortality in tuberculosis (TB. It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb might have genetic traits associated with neurotropism. Methods In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF of patients presenting with tuberculous meningitis (TBM in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. Results Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate/PPE (proline-proline-glutamate, transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. Discussion The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB

  17. Cerebrospinal fluid adenosine deaminase levels as a diagnostic marker in tuberculous meningitis in adult Nepalese patients

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    Anil Chander

    2013-02-01

    Full Text Available Objective: To study the cerebrospinal fluid (CSF adenosine deaminase (ADA levels in tuberculous meningitis (TBM and non-TBM -viral meningitis cases and to determine its diagnostic significance as a biochemical marker of TBM infection.Methods: The study population comprised two different patient groups. TBM - group I - 28 cases and non-TBM-viral meningitis - 22 cases. These were enrolled consecutively in the study and CSF specimens were collected from them. ADA estimation was carried out by spectrophotometry.Results: ADA levels (mean依 SD in the TBM and non-TBM groups were 16.46依6.24 U/L and 5.13依2.96 U/L, respectively (highly significant P10 IU/L, the test showed a good sensitivity of 82.14% (95% CI 64.41-92.12 and a high specificity of 90.91% (95% CI 72.19-97.47. Positive and negative predictive value and positive and negative likelihood ratios and accuracy of the test in TBM cases were 92% (95% CI 75.03-97.77, 80% (95% CI 60.86-91.13, 9.03 (95% CI 2.38- 34.25, 0.19 (95% CI 0.09-0.44 and 86%, respectively.Conclusion: CSF ADA levels are elevated in the TBM cases as compared to the non-TBM - viral meningitis cases with a good sensitivity and a high specificity. It is a simple and inexpensive diagnostic adjunctive test in the rapid and early diagnosis of TBM.

  18. Sodium Bicarbonate Facilitates Hemostasis in the Presence of Cerebrospinal Fluid Through Amplification of Platelet Aggregation.

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    Kozuma, Yukinori; Yamamoto, Tetsuya; Ishikawa, Eiichi; Yoshida, Fumiyo; Akutsu, Hiroyoshi; Matsuda, Masahide; Nakai, Kei; Tsuruta, Wataro; Takano, Shingo; Matsumura, Akira; Ninomiya, Haruhiko

    2016-02-01

    Appropriate hemostasis is essential for clear visualization of the neural structures and cleavage planes. It is also essential for avoiding heat-induced injury, minimizing blood loss, and reducing operative time. To determine the role of cerebrospinal fluid (CSF) in platelet-dependent hemostasis during neurosurgery. The amplification of aggregation, activation of integrin αIIbβ3, intrinsic and extrinsic coagulation pathways, and activation of signaling cascades in platelets were evaluated. For comparison, various concentrations of a commercially available artificial CSF solution (aCSF), an artificial CSF solution prepared by the authors, and normal saline (NS) were used. Differences between aCSF and NS in obtaining in vivo hemostasis were assessed by measuring the tail vein bleeding time in C57BL/6N mice. Platelet aggregation was directly amplified by the addition of aCSF through increased activation of integrin αIIbβ3, phosphatidylserine exposure, and P-selectin expression. However, the prothrombin time and activated partial thromboplastin time were not primarily related to coagulation activity with the addition of aCSF. Activation of Src kinase was related to platelet activation by aCSF. The elimination of sodium bicarbonate from aCSF and the addition of the selective inhibitor of the HCO3/Cl exchanger, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt, significantly inhibited platelet aggregation. The bleeding time in aCSF-treated mice was significantly shorter than that in NS-treated mice. Sodium bicarbonate facilitates hemostasis through the amplification of platelet aggregation function. The existence of CSF and irrigation with aCSF provide better conditions for physiological hemostasis and they have the potential of improving hemostasis by bipolar coagulation or with irrigation during neuroendoscopic procedures.

  19. Clinical manifestations and cerebrospinal fluid status in ocular syphilis in HIV-Negative patients.

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    Dai, Ting; Wu, Xinjun; Zhou, Shaona; Wang, Qianqiu; Li, Daning

    2016-06-06

    Syphilis with ocular involvement has reemerged as a critical health problem. The aim of the present study was to explore the clinical manifestations and cerebrospinal fluid (CSF) status in ocular syphilis in human immunodeficiency virus (HIV)-negative patients. The clinical records of patients with ocular syphilis presenting to the Shanghai Xuhui Central Hospital in the period from January 2011 to December 2012 were retrospectively reviewed. The median age of 25 HIV-negative patients with ocular syphilis was 53 years, 18 patients (72.0 %) were males and 7 (28.0 %) were females. None of them self-identified themselves as men who had sex with men (MSM). The ocular lesions included: uveitis (13 cases), optic neuropathy (6 cases), retinal vasculitis (5 cases), retinal detachment (3 cases), and neuroretinitis (4 cases). Serum toluidine red unheated serum test (TRUST) titer ranged from 1 to 512, with a median of 64. Overall, 18 (72.0 %) of the 25 patients had abnormal CSF results, 15 (60.0 %) CSF samples had elevated white blood cell counts, 13 (52.0 %) had elevated protein levels, and 9 (36.0 %) had reactive CSF Venereal Disease Research Laboratory (VDRL) test, respectively. Mann-Whitney U tests showed higher serum TRUST titer (>32) correlated with the abnormal CSF results. The demographic characteristics of patients with ocular syphilis in this study were different from previous reports. The study showed a high CSF abnormal rate in HIV-negative patients. The recommendation for CSF examination from all patients with ocular syphilis, including HIV-negative cases, is strongly supported by the present data.

  20. Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid.

    Science.gov (United States)

    Bloniecki, Victor; Aarsland, Dag; Blennow, Kaj; Cummings, Jeffrey; Falahati, Farshad; Winblad, Bengt; Freund-Levi, Yvonne

    2017-01-01

    Treatment for neuropsychiatric symptoms (NPS) in dementia is insufficient. Antipsychotics and acetylcholinesterase inhibitors are used generating symptomatic improvements in behavior and cognition, but few studies have investigated their effect on Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). This is a secondary analysis based on an earlier clinical trial comparing the treatment effects on NPS. The aim of this study was to examine whether treatment with risperidone and galantamine affect levels of the biomarkers T-Tau, P-Tau, Aβ1-42, and Aβ42/40-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS. 83 patients (mean + SD 77.9.6±7.7 years) with dementia and NPS were randomized to galantamine (n = 44) or risperidone (n = 39) treatment. CSF samples were collected at baseline and after 12 weeks. Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of Aβ1 - 42 was significantly associated with reduction of irritability at follow up. Low baseline levels of Aβ1-42, Aβ42/40, and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF Aβ1-42 levels in patients treated with risperidone were significantly decreased at follow up, showing an 8% (40 pg/mL) reduction as compared with baseline (p = 0.03). Our results suggest that risperidone may affect the CSF profile of AD biomarkers indicating more amyloid pathology. Treatment with galantamine did not affect the CSF biomarkers in any direction. The AD CSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.

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

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    M.A. Moreira

    2006-04-01

    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.

  2. Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein.

    Science.gov (United States)

    Grangeon, Lou; Paquet, Claire; Bombois, Stephanie; Quillard-Muraine, Muriel; Martinaud, Olivier; Bourre, Bertrand; Lefaucheur, Romain; Nicolas, Gaël; Dumurgier, Julien; Gerardin, Emmanuel; Jan, Mary; Laplanche, Jean-Louis; Peoc'h, Katell; Hugon, Jacques; Pasquier, Florence; Maltête, David; Hannequin, Didier; Wallon, David

    2016-01-01

    Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD. Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001). Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

  3. Frequency of Treponema pallidum invasion into cerebrospinal fluid in primary or secondary early-stage syphilis.

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    Hagihara, Mao; Yamagishi, Yuka; Kato, Hideo; Shibata, Yuichi; Shiota, Arufumi; Sakanashi, Daisuke; Suematsu, Hiroyuki; Watanabe, Hiroki; Asai, Nobuhiro; Koizumi, Yusuke; Furui, Tatsuro; Takahashi, Seiichiro; Izumi, Koji; Mikamo, Hiroshige

    2017-12-08

    Frequency of Treponema pallidum invasion into cerebrospinal fluid (CSF) has not been clear at this present. Since it is impossible to culture T. pallidum in vitro at this present, we need molecular based-approach to detect it in CSF. Additionally, neurosyphilis is usually a late sequela, however it might result in asymptomatic neurosyphilis even at primary or secondary syphilis. This study was to reveal the frequency of T. pallidum invasion into CSF especially at primary or secondary syphilis with polymerase chain reaction (PCR) test. All patients were visited the Aichi Medical University Hospital or Izumi ladies' clinic between 2016 and 2017. Clinical CSF samples were collected from patients with early and late stages of syphilis. The PCR was done using primers targeting the tpN47gene. CSF samples were collected from 9 patients (4 patients with primary syphilis, 3 with secondary syphilis, and 1 early latent syphilis and 1 with late latent syphilis). PCR showed positive reaction in 2 of 7 (28.6%) primary and secondary syphilis patients, in 1 of 1 (100%) early latent syphilis patients, and in 1 of 1 (100%) late latent syphilis patients. Despite its lack of sensitivity for use alone as a diagnostic test, this PCR test should be preferred for the diagnosis of neurosyphilis. Because, T. pallidum was detected in the 28.6% CSF of patients at primary and secondary syphilis, which indicated that they invade the central nervous system from the early stages of infection. However, studies in a larger population are required to confirm these preliminary results. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Detection of Treponema pallidum Sp. Pallidum DNA in Cerebrospinal Fluid (CSF) by Two PCR Techniques.

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    Castro, Rita; Águas, Maria João; Batista, Teresa; Araújo, Carlos; Mansinho, Kamal; Pereira, Filomena da Luz Martins

    2016-09-01

    Laboratory diagnosis of neurosyphilis is complicated especially when it is asymptomatic, no single laboratory test result being appropriate to diagnose central nervous system infectivity caused by Treponema pallidum. Our objective was to evaluate two polymerase chain reaction (PCR) techniques for the detection of T. pallidum DNA in the cerebrospinal fluid (CSF) of patients with syphilis. One hundred twenty-four CSF samples from patients with reactive blood tests for syphilis were obtained. Two PCR techniques (47-PCR, polA-PCR) were used to detect T. pallidum DNA. The laboratory criteria used for the diagnosis of neurosyphilis to which the PCR techniques were compared were those recommended by the IUSTI: 2008 European guidelines on the management of syphilis. Treponema pallidum DNA was detected amplified in 37 of 124 (29.8%) and 30 of 124 (24.2%) samples with the 47-PCR and polA-PCR, respectively. Sensitivities were 75.8% and 69.7% and specificities 86.8% and 92.3%, respectively, for 47-PCR and polA-PCR techniques, respectively. The three CSF samples of patients with primary syphilis did not fulfill the criteria of neurosyphilis and DNA was only detected in one by the 47-PCR. In samples from secondary syphilis and neurosyphilis, three of nine and nine of nine respectively, results were coincident for the two PCR techniques and neurosyphilis criteria. Major discrepancies between the two PCR techniques and neurosyphilis diagnostic criteria were observed in latent syphilis. Beyond some limitations of the study, which are discussed here, both PCR techniques seem to be useful for the diagnosis of neurosyphilis, although 47-PCR presents a higher sensitivity and polA-PCR a higher specificity. © 2016 Wiley Periodicals, Inc.

  5. In vitro study of cerebrospinal fluid dynamics in a shaken basal cistern after experimental subarachnoid hemorrhage.

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    Ulrich Kertzscher

    Full Text Available Cerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters.A model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force.From this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space.

  6. Quantitative measurement of normal and hydrocephalic cerebrospinal fluid flow using phase contrast cine MR imaging

    International Nuclear Information System (INIS)

    Katayama, Shinji; Asari, Shoji; Ohmoto, Takashi

    1993-01-01

    Measurements of the cerebrospinal fluid (CSF) flow using phase contrast cine magnetic resonance (MR) imaging were performed on a phantom, 12 normal subjects and 20 patients with normal pressure hydrocephalus (NPH). The phantom study demonstrated the applicability of phase contrast in quantitative measurement of the slow flow. The CSF flows of the normal subjects showed a consistent pattern with a to-and-fro movement of the flow in the anterior subarachnoid space at the C2/3 level, and they were dependent on the cardiac cycle in all subjects. However, the patients with NPH showed variable patterns of the CSF pulsatile flow and these patterns could be divided into four types according to velocity and amplitude. The amplitudes of each type were as follows: type 0 (n=1), 87.6 mm; type I (n=2), 58.2 mm (mean); type II (n=6), 48.0±5.0 mm (mean±SEM); and type III (n=11), 19.9±1.8 mm (mean±SEM). The decrease of the amplitudes correlated to a worsening of the clinical symptoms. After the shunting operation, the amplitude of to-and-fro movement of the CSF increased again in the patients with NPH who improved clinically. Some of the type III cases were reclassified type II, I and 0 and also one of the type II cases changed type I after the shunting operation. We conclude that the phase contrast cine MR imaging is a practically and clinically applicable technique for the quantitative measurement of the CSF flow. (author)

  7. Time-course of cerebrospinal fluid histamine in the wake-consolidated squirrel monkey.

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    Zeitzer, Jamie M; Kodama, Tohru; Buckmaster, Christine L; Honda, Yoshiko; Lyons, David M; Nishino, Seiji; Mignot, Emmanuel

    2012-04-01

    Central nervous system (CNS) histamine is low in individuals with narcolepsy, a disease characterized by severe fragmentation of both sleep and wake. We have developed a primate model, the squirrel monkey, with which we can examine the role of the CNS in the wake-consolidation process, as these primates are day-active, have consolidated wake and sleep and have cerebrospinal fluid (CSF) that is readily accessible. Using this model and three distinct protocols, we report herein on the role of CNS histamine in the wake consolidation process. CSF histamine has a robust daily rhythm, with a mean of 24.9 ± 3.29 pg mL(-1) , amplitude of 31.7 ± 6.46 pg mL(-1) and a peak at 17:49 ± 70.3 min (lights on 07:00-19:00 hours). These levels are not significantly affected by increases (up to 161 ± 40.4% of baseline) or decreases (up to 17.2 ± 2.50% of baseline) in locomotion. In direct contrast to the effects of sleep deprivation in non-wake-consolidating mammals, in whom CSF histamine increases, pharmacologically induced sleep (γ-hydroxybutyrate) and wake (modafinil) have no direct effects on CSF histamine concentrations. These data indicate that the time-course of histamine in CSF in the wake-consolidated squirrel monkey is robust against variation in activity and sleep and wake-promoting pharmacological compounds, and may indicate that histamine physiology plays a role in wake-consolidation such as is present in the squirrel monkey and humans. © 2011 European Sleep Research Society.

  8. Receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid

    International Nuclear Information System (INIS)

    Walsh, R.J.; Slaby, F.J.; Posner, B.I.

    1987-01-01

    Prolactin (PRL) interacts with areas of the central nervous system which reside behind the blood-brain barrier. While vascular PRL does not cross this barrier, it is readily accessible to the cerebrospinal fluid (CSF) from which it may gain access to the PRL-responsive areas of the brain. Studies were undertaken to characterize the mechanism responsible for the translocation of PRL from blood to CSF. Rats were given external jugular vein injections of [ 125 -I]iodo-PRL in the presence or absence of an excess of unlabeled ovine PRL (oPRL), human GH, bovine GH, or porcine insulin. CSF and choroid plexus were removed 60 min later. CSF samples were electrophoresed on sodium dodecyl sulfate-polyacrylamide slab gels and resultant autoradiographs were analyzed with quantitative microdensitometry. The data revealed that unlabeled lactogenic hormones, viz. oPRL and human GH, caused a statistically significant inhibition of [ 125 I]iodo-PRL transport from blood to CSF. In contrast, nonlactogenic hormones, viz bovine GH and insulin, had no effect on [ 125 I]iodo-PRL transport into the CSF. An identical pattern of competition was observed in the binding of hormone to the choroid plexus. Furthermore, vascular injections of [ 125 I]iodo-PRL administered with a range of concentrations of unlabeled oPRL revealed a dose-response inhibition in the transport of [ 125 I]iodo-PRL from blood to CSF. The study demonstrates that PRL enters the CSF by a specific, PRL receptor-mediated transport mechanism. The data is consistent with the hypothesis that the transport mechanism resides at the choroid plexus. The existence of this transport mechanism reflects the importance of the cerebroventricular system in PRL-brain interactions

  9. Fructose levels are markedly elevated in cerebrospinal fluid compared to plasma in pregnant women.

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    Janice J Hwang

    Full Text Available Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000 th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS fructose production from glucose via the polyol pathway (glucose → sorbitol → fructose contributes to brain exposure to fructose.In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF, maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM undergoing spinal anesthesia and elective cesarean section.As expected, CSF glucose was ~ 60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001, and CSF sorbitol was ~ 9-times higher than plasma levels (p < 0.001. Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02 and sorbitol levels (ρ 0.75, p < 0.001. Cord blood sorbitol was also ~ 7-fold higher than maternal plasma sorbitol levels (p = 0.001. There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.

  10. Cerebrospinal fluid hypovolemia in childhood and adolescence. Clinical features and outcomes

    International Nuclear Information System (INIS)

    Takahashi, Koichi; Mima, Tatsuo

    2011-01-01

    Cerebrospinal fluid (CSF) hypovolemia has increasingly been recognized, but few investigations have examined younger patients. This study investigated 50 cases of CSF hypovolemia onset in childhood and adolescence. We analyzed causes, outcomes, and clinical features of these child and adolescent CSF hypovolemia cases. The 50 patients (25 boys, 25 girls) had shown the onset earlier than age 15. Diagnosis of probable CSF hypovolemia was made basically on clinical symptoms and findings of magnetic resonance imaging (MRI) and Radioisotope (RI) cisternography. For treatment, we defined epidural blood patch (EBP) indication as the early bladder filling (early BF) and all of the 50 cases received EBP. All patients suffered from one or more symptoms such as intractable headache, neck pain, vertigo, fatigue, tinnitus and visual disturbance. These symptoms did not recover with any conventional treatments. Twenty eight cases (56.0%) showed normal results on MRI. In RI cisternography, 16 cases (32.0%) showed CSF leaks (CL), 34 cases (68.0%) showed early BF. About 90% of the patients were improved by EBP. In particular, 96.0% of cases showed good or moderate recovery when onset of CSF hypovolemia and the first treatment was less than 1 year. CSF hypovolemia is not yet well recognized particularly in child and adolescent cases. Some children were misdiagnosed as autonomic nervous system dysfunction, orthostatic dysregulation, Barre-Lieou syndrome or depression. This study indicated that EBP is also effective for younger patients. If patients suffer from various intractable symptoms including orthostatic headache, CSF hypovolemia should be considered for the differential diagnosis. (author)

  11. Cerebrospinal fluid markers in dementia with lewy bodies compared with Alzheimer disease.

    Science.gov (United States)

    Gómez-Tortosa, Estrella; Gonzalo, Isabel; Fanjul, Samira; Sainz, Maria José; Cantarero, Susana; Cemillán, Carlos; Yébenes, Justo García; del Ser, Teodoro

    2003-09-01

    Most patients with dementia with Lewy bodies (DLB) exhibit diffuse plaque-only pathology with rare neocortical neurofibrillary tangles (NFTs), as opposed to the widespread cortical neurofibrillary-tau involvement in Alzheimer disease (AD). Another pathological difference is the astrocytic and microglial inflammatory responses, including release of interleukins (ILs), around the neuritic plaques and NFTs in AD brains that are absent or much lower in DLB. We analyzed cerebrospinal fluid (CSF) markers that reflect the pathological differences between AD and DLB. To determine CSF concentrations of tau, beta-amyloid, IL-1beta, and IL-6 as potential diagnostic clues to distinguish between AD and DLB. We measured total tau, beta-amyloid1-42, IL-1beta, and IL-6 levels in CSF samples of 33 patients with probable AD without parkinsonism, 25 patients with all the core features of DLB, and 46 age-matched controls. Patients with AD had significantly higher levels of tau protein than patients with DLB and controls (P<.001). The most efficient cutoff value provided 76% specificity to distinguish AD and DLB cases. Patients with AD and DLB had lower, but not significantly so, beta-amyloid levels than controls. The combination of tau and beta-amyloid levels provided the best sensitivity (84%) and specificity (79%) to differentiate AD vs controls but was worse than tau values alone in discriminating between AD and DLB. Beta-amyloid levels had the best correlation with disease progression in both AD and DLB (P =.01). There were no significant differences in IL-1beta levels among patients with AD, patients with DLB, and controls. Patients with AD and DLB showed slightly, but not significantly, higher IL-6 levels than controls. The tau levels in CSF may contribute to the clinical distinction between AD and DLB. Beta-amyloid CSF levels are similar in both dementia disorders and reflect disease progression better than tau levels. Interleukin CSF concentrations do not distinguish between

  12. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

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    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  13. Effect of the drainage of cerebrospinal fluid in patients with aneurismal subarachnoid hemorrhage

    Science.gov (United States)

    Qian, Cong; Yu, Xiaobo; Chen, Jingyin; Gu, Chi; Wang, Lin; Chen, Gao; Dai, Yuying

    2016-01-01

    Abstract Background and objectives: Vasospasm-related injury such as delayed ischemic neurological defect (DIND) or cerebral infarction is an important prognostic factor for aneurismal subarachnoid hemorrhage (SAH). Whether cerebrospinal fluid (CSF) drainage can achieve a better outcome in aneurismal SAH patients after coiling or clipping remains the subject of debate. Here, we report a meta-analysis of the related available literature to assess the effect of continuous CSF drainage on clinical outcomes in patients with aneurismal SAH. Methods: Case-control studies regarding the association between aneurismal SAH and CSF drainage were systematically identified through online databases (PubMed, Web of Science, Elsevier Science Direct, and Springer Link). Inclusion and exclusion criteria were defined for the eligible studies. The fixed-effects model was performed when homogeneity was indicated. Alternatively, the random-effects model was utilized. Results: This meta-analysis included 11 studies. Continuous CSF drainage obviously improved patients’ long-term outcome (odds ratio [OR] of 2.86, 95% confidence interval [CI], 1.37–5.98, P drainage also reduced angiographic vasospasm (OR of 0.35, 95% CI, 0.23–0.51, P drainage group and the no CSF drainage group on shunt-dependent hydrocephalus (SDHC) prevention (OR of 1.04, 95% CI, 0.52–2.07, P = 0.91). Further analysis on lumbar drainage (LD) and external ventricular drainage (EVD) indicated that LD had a better outcome (OR of 3.11, 95% CI, 1.18–8.23, P = 0.02), whereas no significant difference in vasospasm-related injury was detected between the groups (OR of 1.13, 95% CI, 0.54–2.37, P = 0.75). Conclusion: Continuous CSF drainage is an effective treatment for aneurismal SAH patients; lumbar drainage showed lower complications, but more well-designed studies are required to verify and consolidate this conclusion. PMID:27741143

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

    Science.gov (United States)

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês; Tsolaki, Magda; Gkatzima, Olymbia; Sermin, Genc; Yener, Görsev G; Simonsen, Anja; Hasselbalch, Steen G; Kapaki, Elisabeth; Mara, Bourbouli; Cunha, Rodrigo A; Agostinho, Paula; Blennow, Kaj; Zetterberg, Henrik; Mendes, Vera M; Manadas, Bruno; de Mendon, Alexandreça

    2015-01-01

    Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau 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 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.

  15. Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria.

    Science.gov (United States)

    Thakur, Kiran T; Vareta, Jimmy; Carson, Kathryn A; Kampondeni, Samuel; Potchen, Michael J; Birbeck, Gretchen L; MacCormick, Ian; Taylor, Terrie; Sullivan, David J; Seydel, Karl B

    2018-03-23

    Cerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM. Patients included in the study were admitted (2009-2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization. In this cohort of 94 patients, median age was 44 (interquartile range 29-62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44-56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45-9.35). Elevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.

  16. Risk factors for postoperative cerebrospinal fluid leak and meningitis after expanded endoscopic endonasal surgery.

    Science.gov (United States)

    Ivan, Michael E; Iorgulescu, J Bryan; El-Sayed, Ivan; McDermott, Michael W; Parsa, Andrew T; Pletcher, Steven D; Jahangiri, Arman; Wagner, Jeffrey; Aghi, Manish K

    2015-01-01

    Postoperative cerebrospinal fluid (CSF) leak is a serious complication of transsphenoidal surgery, which can lead to meningitis and often requires reparative surgery. We sought to identify preoperative risk factors for CSF leaks and meningitis. We reviewed 98 consecutive expanded endoscopic endonasal surgeries performed from 2008-2012 and analyzed preoperative comorbidities, intraoperative techniques, and postoperative care. Univariate and multivariate analyses were performed. The most common pathologies addressed included pituitary adenoma, Rathke cyst, chordoma, esthesioneuroblastoma, meningioma, nasopharyngeal carcinoma, and squamous cell carcinoma. There were 11 CSF leaks (11%) and 10 central nervous system (CNS) infections (10%). Univariate and multivariate analysis of preoperative risk factors showed that patients with non-ideal body mass index (BMI) were associated with higher rate of postoperative CSF leak and meningitis (both p<0.01). Also, patients with increasing age were associated with increased CSF leak (p = 0.03) and the length of time a lumbar drain was used postoperatively was associated with infection in a univariate analysis. In addition, three of three endoscopic transsphenoidal surgeries combined with open cranial surgery had a postoperative CSF leak and CNS infection rate which was a considerably higher rate than for transsphenoidal surgeries alone or surgeries staged with open cases (p<0.01 and p=0.04, respectively) In this series of expanded endoscopic transsphenoidal surgeries, preoperative BMI remains the most important preoperative predictor for CSF leak and infection. Other risk factors include age, intraoperative CSF leak, lumbar drain duration, and cranial combined cases. Risks associated with complex surgical resections when combining open and endoscopic approaches could be minimized by staging these procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Performance of Aspergillus PCR in cerebrospinal fluid for the diagnosis of cerebral aspergillosis.

    Science.gov (United States)

    Imbert, S; Brossas, J-Y; Palous, M; Joly, I; Meyer, I; Fekkar, A

    2017-11-01

    Cerebral aspergillosis is a rare but often fatal form of invasive aspergillosis that remains difficult to diagnose. The literature has shown the value of Aspergillus PCR in blood-derived samples for the diagnosis of invasive aspergillosis but provides far less information for cerebrospinal fluid (CSF) in cerebral aspergillosis. Here, we evaluated the usefulness of an Aspergillus PCR assay performed on CSF for the diagnosis of cerebral aspergillosis. This retrospective study involved 72 patients with suspected cerebral aspergillosis for a total of 88 CSF samples in whom CSF Aspergillus PCR was performed. Seventeen patients had proven/probable invasive aspergillosis according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, including 12 cases of proven/probable cerebral aspergillosis. Aspergillus PCR in CSF was positive in nine of the twelve patients with cerebral aspergillosis, i.e. 75% sensitivity. In contrast, CSF culture was positive for Aspergillus in only two patients. In the non-cerebral aspergillosis group (60 patients), PCR was positive in one patient, i.e. 98.3% specificity. In this particular population of high-risk patients with suspicion of cerebral aspergillosis, the disease incidence was 16.7%. Therefore, the positive and negative predictive values of PCR were 90% and 95.2%, respectively. The results of this study indicate that Aspergillus PCR in CSF is an interesting tool that may eliminate the need for cerebral biopsy in patients with suspected cerebral aspergillosis. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Cerebrospinal Fluid and Microdialysis Cytokines in Aneurysmal Subarachnoid Hemorrhage: A Scoping Systematic Review

    Directory of Open Access Journals (Sweden)

    Frederick A. Zeiler

    2017-08-01

    Full Text Available ObjectiveTo perform two scoping systematic reviews of the literature on cytokine measurement in cerebral microdialysis (CMD and cerebrospinal fluid (CSF in aneurysmal subarachnoid hemorrhage (SAH patients, aiming to summarize the evidence relating cytokine levels to pathophysiology, disease progression, and outcome.MethodsTwo separate systematic reviews were conducted: one for CMD cytokines and the second for CSF cytokines.Data sourcesArticles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016, reference lists of relevant articles, and gray literature were searched.Study selectionTwo reviewers independently identified all manuscripts utilizing predefined inclusion/exclusion criteria. A two-tier filter of references was conducted.Data extractionPatient demographic and study data were extracted to tables.ResultsThere were 9 studies identified describing the analysis of cytokines via CMD in 246 aneurysmal SAH patients. Similarly, 20 studies were identified describing the analysis of CSF cytokines in 630 patients. The two scoping systematic reviews demonstrated the following: (1 limited literature available on CMD cytokine measurement in aneurysmal SAH with some preliminary data supporting feasibility of measurement and potential association between interleukin (IL-6 and patient outcome. (2 Various CSF measured cytokines may be associated with patient outcome at 3–6 months, including IL-1ra, IL-6, IL-8, and tumor necrosis factor-alpha. (3 There is a small literature body supporting an association between acute/subacute CSF transforming growth factor levels and the development of chronic hydrocephalus at 2–3 months.ConclusionThe evaluation of CMD and CSF cytokines is an emerging area of the literature in aneurysmal SAH. Further large prospective multicenter studies on cytokines in CMD and CSF need to be conducted.

  19. A tomographic study of the skull base in primary spontaneous cerebrospinal fluid leaks

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    Giannetti, Alexandre Varella [Hospital das Clinicas, Service of Neurosurgery, Belo Horizonte (Brazil); Federal University of Minas Gerais, Department of Surgery, School of Medicine, Belo Horizonte (Brazil); Guimaraes, Roberto Eustaquio S. [Hospital das Clinicas, Services Otorhinolaryngology, Belo Horizonte (Brazil); Federal University of Minas Gerais, Department of Ophthalmology and Otorhinolaryngology, School of Medicine, Belo Horizonte (Brazil); Santiago, Ana Paula M.S. [Hospital das Clinicas, Services Radiology, Belo Horizonte (Brazil); Perpetuo, Francisco Otaviano L.; Machado, Marco Antonio O. [Computed Tomography Center of Minas Gerais, Belo Horizonte (Brazil)

    2012-05-15

    This study aims to evaluate the existence of anatomic abnormalities in the skull base that could contribute to the origin of primary spontaneous cerebrospinal fluid leaks (PSL). Twenty PSL patients were compared with 20 healthy individuals. The following features were measured through an analysis of computed tomography scans: the angles of the petrosal bones and skull base in both the sagittal and coronal planes; the anteroposterior and mediolateral diameters of the anterior skull base, sella, and sphenoid sinus; the depth of the olfactory fossa; the pneumatization of the sphenoid sinus; the position of the crista galli; and the state of the dorsum sellae. Body mass index (BMI) was compared. There were no differences between the two groups with respect to the angles and diameters of the anterior cranial fossa and the sphenoid sinus or the depth of the olfactory fossa. Pneumatization of the lateral recess of the sphenoid sinus was more frequent in the PSL group (55%) than in the control group (25%, p = 0.053). The dorsum sellae were eroded in 30% of the PSL patients but intact in all healthy subjects. PSL subjects showed higher sellae (1.0 versus 0.8 cm, p = 0.002). The average BMI of PSL patients was higher than that of the control group. Global alterations in the skull base of PSL patients were not found. The increase in the height of sellae and the erosion of its dorsum suggest intracranial hypertension. The higher BMI in the case group confirms the relation between obesity and PSL. (orig.)

  20. Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus.

    Science.gov (United States)

    Khalili-Fomeshi, Mohsen; Azizi, Mohammad Golparvar; Esmaeili, Mohammad Reza; Gol, Mohammad; Kazemi, Sohrab; Ashrafpour, Manouchehr; Moghadamnia, Ali Akbar; Hosseinzadeh, Soheila

    2018-01-30

    Piperine has been shown to have antioxidant activity and a cognitive-enhancing effect following long-term oral administration. In a comparative study of memantine, the current investigation threw light on the cognitive benefits of piperine. Lipid peroxidation and the ferric reducing antioxidant power (FRAP) of cerebrospinal fluid (CSF) and hippocampus in streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type was measured. After reaching a criterion in a memory test, STZ-induced rats received piperine [2.5, 5, and 10mg/kg, intraperitoneally (i.p.)], vehicle, and memantine (10mg/kg, i.p.) for two weeks after the first STZ administration, or two weeks before and one week after, as a preventive approach. After the behavioral studies, samples were taken for biochemical and histological assays. An appropriate concentration of piperine (2.5mg/kg), on a daily basis, effectively increased the number of correct (non-repeated) arm entries and repressed reentry to a previously visited arm, in terms of reference errors as well as memantine (10mg/kg, i.p.), irrespective of the dose administered. The cognitive-enhancing effect induced by piperine at a relevant dose was simultaneous with CSF and hippocampal malonaldehyde decrement, and the redox balance was established to some extent by maintaining the FRAP levels of CSF near to those of the control. Similarly, the neuroprotective properties of piperine are in accordance with histopathological outcomes, which have shown an increased number of live cresyl violet (CV)-positive neurons in a dentate gyrus (DG) subregion. Therefore, the effects of piperine on the redox balance of CSF and hippocampal neurons may certainly contribute to the cognitive-enhancing activity of the drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Association of benign intracranial hypertension and spontaneous encephalocele with cerebrospinal fluid leak.

    Science.gov (United States)

    Brainard, Laura; Chen, Douglas A; Aziz, Khaled M; Hillman, Todd A

    2012-12-01

    To determine the incidence of intracranial hypertension in patients with spontaneous encephalocele with cerebrospinal fluid (CSF) leak. Retrospective case review. Tertiary care neurotology practice. Patients presenting between 2008 and 2011 with spontaneous encephalocele and CSF leak in the temporal bone. Lumbar puncture with opening pressure measurement after encephalocele repair. Patient age, sex, postoperative course, body mass index, and postoperative intracranial pressure. Of the 26 patients identified with spontaneous encephalocele with CSF leak, 9 patients had postoperative lumbar puncture data. Of those 9, 89% were female subjects, and 11% were male, with a mean age of 57 and a mean BMI of 41 kg/m (morbidly obese). The mean opening pressure was 24.5 cm H(2)O. Approximately 33% had normal intracranial pressure (mean, 15 cm H(2)O; range, 10-17 cm H(2)O); 67% had elevated intracranial pressure (mean, 29 cm H(2)O; range, 23.5-40 cm H(2)O). The incidence of BIH in the general population is 0.001%. Of the 6 with intracranial hypertension, 3 (50%) were placed on acetazolamide for fundoscopic findings, postoperative headache, and/or visual changes. Mean time to LP after repair of encephalocele was 13 months (range, 4 days to 75 months). This study shows that benign intracranial hypertension is prevalent in a significant number of patients presenting with spontaneous encephalocele with CSF otorrhea at a rate much higher than is found in the general population. This finding has direct clinical implications and suggests that all patients with spontaneous encephalocele/CSF leak warrant evaluation for benign intracranial hypertension.

  2. Cerebrospinal Fluid Total Protein Reference Intervals Derived from 20 Years of Patient Data.

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    McCudden, Christopher R; Brooks, John; Figurado, Priya; Bourque, Pierre R

    2017-12-01

    Reference intervals are vital for interpretation of laboratory results. Many existing reference intervals for cerebrospinal fluid total protein (CSF-TP) are derived from old literature because of the invasive nature of sampling. The objective of this study was to determine reference intervals for CSF-TP using available patient data. Twenty years of hospital database information was mined for previously reported CSF-TP results. Associated demographic, laboratory, and clinical diagnosis (International Classification of Diseases 9/10 codes) details were extracted. CSF-TP results included 3 different analytical platforms: the Siemens Vista 1500, Beckman Lx20, and Roche Hitachi 917. From an initial data set of 19591 samples, the following exclusion criteria were applied: incomplete data, white blood cells (WBCs) >5 × 10 6 /L, red blood cells (RBCs) >50 × 10 6 /L, and glucose reference intervals were determined using quantile regression. Age- and sex-partitioned intervals were established using the quantile regression equation and splitting age-groups into 5-year bins. CSF-TP showed a marked age dependence, and males had significantly higher CSF-TP than females across all ages. CSF-TP results from the 3 different instruments and manufacturers showed small (approximately 0.04 g/L), but statistically significant, differences. CSF-TP showed weak, but again statistically significant, correlation with WBC and RBC but was independent of serum total protein and creatinine. The age dependence of CSF-TP supports that age-partitioned reference intervals will be more accurate than a single cutoff, particularly in patients with advancing age. © 2017 American Association for Clinical Chemistry.

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

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    Ronald C Hendrickson

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

  4. An improved specimens handling procedure for pathogen detection of the cerebrospinal fluid by microscope

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    WANG Hua-cheng

    2013-02-01

    Full Text Available Background The diagnosis of encephalitis depends on the finding of pathogens in the brain parenchyma or cerebrospinal fluid (CSF. But the success rates of finding pathogens by microscope are low by the traditional specimens handling procedure in which pathogens are detected by direct centrifugation of CSF getting from lumbar puncture. The process of pathogen collection from the CSF such as centrifugation and washing would cause the destruction and loss of pathogens, resulting in a lower rate of pathogen discovery. Therefore, in order to increase the detection rate of pathogenic microorganisms in CSF, these traditional steps need to be improved. Methods CSF samples of 23 patients with suspected viral encephalitis and 10 control patients with fracture were prepared by two methods: traditional specimens handling procedure (TSHP and improved specimens handling procedure (ISHP. In the ISHP, a final concentration of 2.5% glutaraldehyde was added to CSF in a glass tube, mixed and kept not moving in 4 ℃ for 2 to 4 h or in 37 ℃for 1 h. Then a smear was made from the sediment formed in the tube to check pathogens by microscope. As for the TSHP, pathogens were collected by direct centrifugation of CSF which had not been treated after lumbar puncture, and checked through Gimenze staining. Results There was no statistically significant difference between the two dealing procedures in the control group ( P = 1.000. As for the case group, there were 10 cases showing positive in Pandy test after TSHP, and visible sediments were seen in all the 23 cases after ISHP. There was statistically significant difference between two kinds of CSF treatment for the finding of pathogens (P = 0.000. Seven cases presented pathogen growth in CSF and were diagosed as rickettsial infections by Gimenze staining, immunofluorescence assay (IFA and polymerase chain reaction (PCR. Conclusion Improved specimens handling procedures of CSF contribute to the seperation of cells

  5. Usefulness of blood and cerebrospinal fluid laboratory testing to predict bacterial meningitis in the emergency department.

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    Julián-Jiménez, A; Morales-Casado, M I

    2016-07-25

    The classic clinical presentation of bacterial meningitis (BM) is observed in less than half of the cases in adults, and symptoms are less specific in children, the elderly or immunocompromised, and other chronic patients. The usual signs and symptoms do not provide optimal sensitivity and specificity for distinguishing possible BM from viral meningitis (VM), which may lead to a delay in the appropriate antimicrobial therapy. Society therefore stands to benefit from the development of effective, objective, and rapid tools able to predict and identify patients with BM. These tools include laboratory tests for blood and cerebrospinal fluid (CSF). The aim of this review is to summarise recently published scientific evidence in order to clarify existing controversies and compare the usefulness and diagnostic ability of the different parameters used to predict BM. Systematic search of the main bibliographic databases and platforms to identify articles published between January 2000 and January 2016. We selected 59 articles that meet the objectives of this review. CSF lactate, proportion of polymorphonuclear leukocytes, and CSF glucose, as well as serum procalcitonin (PCT), are the independent factors most predictive of bacterial aetiology. The model that combines serum PCT and CSF lactate achieves the highest predictive power for BM, with a sensitivity and specificity exceeding 99%. We should consider BM when CSF lactate >33 md/dL and/or PCT>0.25ng/mL. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

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    Petropoulos Christos J

    2005-11-01

    Full Text Available Abstract Background Central nervous system (CNS exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1 progression of systemic infection, 2 CSF white blood cell (WBC count, 3 antiretroviral therapy (ART, and 4 neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL. CSF HIV viral loads (VLs correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

  7. Endostatin/Collagen XVIII Is Increased in Cerebrospinal Fluid after Severe Traumatic Brain Injury

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    Hao Chen

    2013-01-01

    Full Text Available Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI. In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF of 30 patients with TBI and a Glasgow Coma Scale (GCS score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3–5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6–8 (P<0.05 and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P=0.043 and day 7 (P=0.005 after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546.

  8. Concordance between cerebrospinal fluid biomarkers and [11C]PIB PET in a memory clinic cohort.

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    Zwan, Marissa; van Harten, Argonde; Ossenkoppele, Rik; Bouwman, Femke; Teunissen, Charlotte; Adriaanse, Sofie; Lammertsma, Adriaan; Scheltens, Philip; van Berckel, Bart; van der Flier, Wiesje

    2014-01-01

    Two approaches are available for measuring Alzheimer's disease (AD) pathology in vivo. Biomarkers in cerebrospinal fluid (CSF) include amyloid-β1-42 (Aβ42) and tau. Furthermore, amyloid deposition can be visualized using positron emission tomography (PET) and [11C]Pittsburgh compound-B ([11C]PIB). We investigated concordance between CSF biomarkers and [11C]PIB PET as markers for AD pathology in a memory clinic cohort. We included 64 AD patients, 34 non-AD dementia patients, 22 patients with mild cognitive impairment (MCI), and 16 controls. [11C]PIB scans were visually rated as positive or negative. CSF biomarkers were considered abnormal based on Aβ42 alone ( 1). Concordance between CSF biomarkers and [11C]PIB PET was determined. Overall, concordance between [11C]PIB PET and CSF Aβ42 (PIB PET was more often AD-positive than Aβ42. When a more lenient Aβ42 cut-point (PIB PET appeared to be even higher (90% and 89%). This difference is explained by a subgroup of mostly MCI and AD patients with Aβ42 levels just above cut-off. Now, in discordant cases, CSF was more often AD-positive than [11C]PIB PET. Concordance between CSF Aβ42 and [11C]PIB PET was good in all diagnostic groups. Discordance was mostly seen in MCI and AD patients close to the cut-point. These results provide convergent validity for the use of both types of biomarkers as measures of AD pathology.

  9. Neurotransmitter measures in the cerebrospinal fluid of patients with Alzheimer's disease: a review.

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    Strac, Dubravka Svob; Muck-Seler, Dorotea; Pivac, Nela

    2015-03-01

    Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by progressive cognitive and functional decline, as well as by a variety of neuropsychiatric and psychological symptoms and behavioral dysfunctions. Various studies proposed the role of different neurotransmitter systems not only in AD-related cognitive, but also psychotic symptoms and behavioral and emotional deficits. Due to the close proximity, pathological neurochemical changes in brain occurring in AD are likely to be reflected in the cerebrospinal fluid (CSF). The purpose of this review is to provide a summary of the CSF neurotransmitter correlates of AD in order to get further insights into the potential role of altered neurotransmitters in the pathophysiology of AD and to offer novel AD biomarkers. PubMed and MEDLINE data bases were searched for English-language articles by using "Alzheimer's disease", "CSF" and "neurotransmitter" as primary terms. No time or article type constraints were applied. Moreover, the lists of references were searched manually for additional articles. Changes in various correlates of cholinergic, monoaminergic and amino acid neurotransmitter systems, as well as neuropeptides, have been observed in CSF of AD patients. However, as the results of these studies have been controversial, the importance of CSF neurotransmitter parameters as potential biomarkers in AD remains quite unclear. The observed discrepancies could be bypassed by implementation of new sensitive methods, such as novel proteomics approaches that include protein separation techniques, mass spectroscopy and targeted multiplex panels of specific analytes. Although no individual CSF neurotransmitter correlate was demonstrated as suitable biomarker of AD, a combined profile of several CSF neurochemical parameters might show enhanced sensitivity and specificity and thus contribute to earlier and more accurate diagnosis of AD, crucial for application of effective treatments.

  10. Low cerebrospinal fluid hypocretin levels during sudden infant death syndrome (SIDS) risk period.

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    Lancien, Marion; Inocente, Clara Odilia; Dauvilliers, Yves; Kugener, Beatrice; Scholz, Sabine; Raverot, Veronique; Lin, Jian-Sheng; Guyon, Aurore; Gustin, Marie-Paule; Franco, Patricia

    2017-05-01

    The temporal association between sudden infant death syndrome (SIDS) and sleep suggests that the arousability from sleep provides a protective mechanism for survival. Recently, the hypocretin system, which promotes wakefulness, has been implicated in SIDS, since it has been reported that SIDS victims have fewer hypocretin neurons than infants who have died from other causes. To understand the role of hypocretin in SIDS, it is essential to better understand how this system matures. The present study compared cerebrospinal fluid (CSF) hypocretin in children aged 2-6 months, which is the age of peak incidence for SIDS, to both younger and older children. Hypocretin levels were measured in CSF samples from 101 children who underwent a clinically relevant lumbar puncture. Children were separated into five age groups: 0-2 months, 2-6 months, 1-5 years, 5-10 years, and 10-18 years. Hypocretin levels were not significantly different between 1-5 years, 5-10 years, and 10-18 years. Therefore, these three groups were pooled into a single one (1-18 years) for further analysis. Between the 0-2 month, 2-6 month, and 1-18 year groups, a significant difference in CSF hypocretin levels existed (p = 0.001). Simple comparisons showed that CSF hypocretin levels in the 2-6 month age group were significantly lower than hypocretin levels in both the 0-2 month and 1-18 year group (p hypocretin levels were lower at the age of peak incidence for SIDS. This could underlie an increased vulnerability to SIDS at this specific age. Copyright © 2017. Published by Elsevier B.V.

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

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    Kim Boddum

    Full Text Available The hypocretin/orexin neuropeptides (hcrt are key players in the control of sleep and wakefulness evidenced by the fact that lack of hcrt leads to the sleep disorder Narcolepsy Type 1. Sleep disturbances are common in mood disorders, and hcrt has been suggested to be poorly regulated in depressed subjects. To study seasonal variation in hcrt levels, we obtained data on hcrt-1 levels in the cerebrospinal fluid (CSF from 227 human individuals evaluated for central hypersomnias at a Danish sleep center. The samples were taken over a 4 year timespan, and obtained in the morning hours, thus avoiding impact of the diurnal hcrt variation. Hcrt-1 concentration was determined in a standardized radioimmunoassay. Using biometric data and sleep parameters, a multivariate regression analysis was performed. We found that the average monthly CSF hcrt-1 levels varied significantly across the seasons following a sine wave with its peak in the summer (June-July. The amplitude was 19.9 pg hcrt/mL [12.8-26.9] corresponding to a 10.6% increase in midsummer compared to winter. Factors found to significantly predict the hcrt-1 values were day length, presence of snow, and proximity to the Christmas holiday season. The hcrt-1 values from January were much higher than predicted from the model, suggestive of additional factors influencing the CSF hcrt-1 levels such as social interaction. This study provides evidence that human CSF hcrt-1 levels vary with season, correlating with day length. This finding could have implications for the understanding of winter tiredness, fatigue, and seasonal affective disorder. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation.

  12. Biochemical alterations in cerebrospinal fluid during thoracoabdominal aortic cross-clamping in dogs.

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    Nagy, G; Dzsinich, Cs; Selmeci, L; Sepa, G; Dzsinich, M; Kékesi, V; Juhász-Nagy, A

    2002-07-01

    Spinal cord damage during and after thoracoabdominal aortic cross-clamping continues to be a major problem. Somatosensory and motor evoked potentials have been used to monitor spinal cord function but their value for predicting paraplegia has been controversial. The aim of this study was to measure biochemical markers in the cerebrospinal fluid (CSF) and correlate changes with spinal cord ischemia. Since neural tissue utilizes only glucose as substrate for its metabolism and energy supply, we measured changes of metabolites of anaerobe glycolysis. In a canine model in which general anesthesia was used, the thoracoabdominal aorta was cross-clamped proximally and distally for 60 min. Hemodynamic parameters, blood gases, and glucose level were monitored continuously. Blood and CSF sampling were performed at baseline, at 15, 30, and 55 min during cross-clamping, and at 5 and 15 min after aortic declamping. Levels of lactate (1.7 +/- 0.1 to 3.2 +/- 0.3 mmol/L), pCO2 (43 +/- 2 to 35 +/- 1.6 mmHg), and neuron-specific enolase (NSE) (5.17 +/- 0.5 to 13.0 +/- 3.5 mg/L) in CSF showed significant changes (p < 0.05) during clamping and reperfusion. Changes in CSF lactate and NSE levels correlate with the duration of spinal cord ischemia. These markers of ischemic metabolism appear suitable to monitor the degree of spinal cord ischemia during thoracoabdominal cross-clamping and may be useful to predict the efficacy of preventive methods.

  13. Concordance between brain 18F-FDG PET and cerebrospinal fluid biomarkers in diagnosing Alzheimer's disease.

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    Rubí, S; Noguera, A; Tarongí, S; Oporto, M; García, A; Vico, H; Espino, A; Picado, M J; Mas, A; Peña, C; Amer, G

    Cortical posterior hypometabolism on PET imaging with 18 F-FDG (FDG-PET), and altered levels of Aß 1-42 peptide, total Tau (tTau) and phosphorylated Tau (pTau) proteins in cerebrospinal fluid (CSF) are established diagnostic biomarkers in Alzheimer's disease (AD). An evaluation has been made of the concordance and relationship between the results of FDG-PET and CSF biomarkers in symptomatic patients with suspected AD. A retrospective review was carried out on 120 patients with cognitive impairment referred to our Cognitive Neurology Unit, and who were evaluated by brain FDG-PET and a lumbar puncture for CSF biomarkers. In order to calculate their Kappa coefficient of concordance, the result of the FDG-PET and the set of the three CSF biomarkers in each patient was classified as normal, inconclusive, or AD-compatible. The relationship between the results of both methods was further assessed using logistic regression analysis, including the Aß 1-42 , tTau and pTau levels as quantitative predictors, and the FDG-PET result as the dependent variable. The weighted Kappa coefficient between FDG-PET and CSF biomarkers was 0.46 (95% CI: 0.35-0.57). Logistic regression analysis showed that the Aß 1-42 and tTau values together were capable of discriminating an FDG-PET result metabolically suggestive of AD from one non-suggestive of AD, with a 91% sensitivity and 93% specificity at the cut-off line Aß 1-42 =44+1.3×tTau. The level of concordance between FDG-PET and CSF biomarkers was moderate, indicating their complementary value in diagnosing AD. The Aß 1-42 and tTau levels in CSF help to predict the patient FDG-PET cortical metabolic status. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  14. Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta.

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    Oikonomidi, Aikaterini; Lewczuk, Piotr; Kornhuber, Johannes; Smulders, Yvo; Linnebank, Michael; Semmler, Alexander; Popp, Julius

    2016-10-01

    Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. The objective of this study was to investigate the relationships between cerebral amyloid production and both blood and cerebrospinal fluid (CSF) markers of the homocysteine metabolism. We assessed CSF concentrations of soluble APPα, soluble APPβ, and amyloid β1-42 (Aβ1-42), as well as plasma levels of homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of homocysteine (Hcys-CSF), 5-methyltetrahydrofolate (5-MTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) in 59 subjects with normal cognition. Linear regression analyses were performed to assess associations between homocysteine metabolism parameters and amyloid production. The study was approved by the Ethical Committee of the University of Bonn. After controlling for age, gender, APOEe4 status, and albumin ratio (Qalb), higher Aβ1-42 CSF levels were associated with high Hcys and low vitamin B12 plasma levels as well as with high Hcys, high SAH, and low 5-MTHF CSF levels. Higher CSF concentrations of sAPPα and sAPPβ were associated with high SAH levels. The results suggest that disturbed homocysteine metabolism is related to increased CSF levels of sAPP forms and Aβ1-42, and may contribute to the accumulation of amyloid pathology in the brain. Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. We found associations between CSF levels of soluble APP forms and Aβ1-42, and markers of the homocysteine metabolism in both plasma and CSF in adults with normal cognition. Disturbed homocysteine metabolism may represent a target for preventive and early disease-modifying interventions in Alzheimer's disease. © 2016 International Society for Neurochemistry.

  15. Increased Concentrations of Interleukin-33 in the Serum and Cerebrospinal Fluid of Patients with Multiple Sclerosis

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    Abdollah Jafarzadeh

    2016-01-01

    Full Text Available Objectives: Interleukin (IL-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF IL-33 concentrations in patients with multiple sclerosis (MS. Methods: Blood specimens were obtained from 140 patients with MS (46 males and 94 females with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females, who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. Results: The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p<0.001 and p<0.050, respectively. The serum IL-33 concentrations were also significantly higher in newly diagnosed (untreated patients and patients treated with methylprednisolone or with interferon-β and methylprednisolone compared to the healthy patient group (p<0.007, p<0.002, and p<0.010, respectively. Moreover, the serum IL-33 concentrations in patients with relapsing-remitting (RRMS, primary progressive (PPMS, and secondary progressive (SPMS forms of the disease were significantly higher than in the healthy control group (p<0.006, p<0.001, and p<0.020, respectively. Conclusions: Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-β plus methylprednisolone has no influence on IL-33 concentrations.

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

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    Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan; Arai, Hiroyuki; Batish, Sat Dev; Bernardini, Sergio; Bocchio-Chiavetto, Luisella; Blankenstein, Marinus A.; Carrillo, Maria C.; Chalbot, Sonia; Coart, Els; Chiasserini, Davide; Cutler, Neal; Dahlfors, Gunilla; Duller, Stefan; Fagan, Anne M.; Forlenza, Orestes; Frisoni, Giovanni B.; Galasko, Douglas; Galimberti, Daniela; Hampel, Harald; Handberg, Aase; Heneka, Michael T.; Herskovits, Adrianna Z.; Herukka, Sanna-Kaisa; Holtzman, David M.; Humpel, Christian; Hyman, Bradley T.; Iqbal, Khalid; Jucker, Mathias; Kaeser, Stephan A.; Kaiser, Elmar; Kapaki, Elisabeth; Kidd, Daniel; Klivenyi, Peter; Knudsen, Cindy S.; Kummer, Markus P.; Lui, James; Lladó, Albert; Lewczuk, Piotr; Li, Qiao-Xin; Martins, Ralph; Masters, Colin; McAuliffe, John; Mercken, Marc; Moghekar, Abhay; Molinuevo, José Luis; Montine, Thomas J.; Nowatzke, William; O’Brien, Richard; Otto, Markus; Paraskevas, George P.; Parnetti, Lucilla; Petersen, Ronald C.; Prvulovic, David; de Reus, Herman P. M.; Rissman, Robert A.; Scarpini, Elio; Stefani, Alessandro; Soininen, Hilkka; Schröder, Johannes; Shaw, Leslie M.; Skinningsrud, Anders; Skrogstad, Brith; Spreer, Annette; Talib, Leda; Teunissen, Charlotte; Trojanowski, John Q.; Tumani, Hayrettin; Umek, Robert M.; Van Broeck, Bianca; Vanderstichele, Hugo; Vecsei, Laszlo; Verbeek, Marcel M.; Windisch, Manfred; Zhang, Jing; Zetterberg, Henrik; Blennow, Kaj

    2013-01-01

    Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer’s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer’s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTESTenzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers. PMID:21784349

  17. Incorporating and Compensating Cerebrospinal Fluid in Surface-Based Forward Models of Magneto- and Electroencephalography.

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    Matti Stenroos

    Full Text Available MEG/EEG source imaging is usually done using a three-shell (3-S or a simpler head model. Such models omit cerebrospinal fluid (CSF that strongly affects the volume currents. We present a four-compartment (4-C boundary-element (BEM model that incorporates the CSF and is computationally efficient and straightforward to build using freely available software. We propose a way for compensating the omission of CSF by decreasing the skull conductivity of the 3-S model, and study the robustness of the 4-C and 3-S models to errors in skull conductivity. We generated dense boundary meshes using MRI datasets and automated SimNIBS pipeline. Then, we built a dense 4-C reference model using Galerkin BEM, and 4-C and 3-S test models using coarser meshes and both Galerkin and collocation BEMs. We compared field topographies of cortical sources, applying various skull conductivities and fitting conductivities that minimized the relative error in 4-C and 3-S models. When the CSF was left out from the EEG model, our compensated, unbiased approach improved the accuracy of the 3-S model considerably compared to the conventional approach, where CSF is neglected without any compensation (mean relative error 40%. The error due to the omission of CSF was of the same order in MEG and compensated EEG. EEG has, however, large overall error due to uncertain skull conductivity. Our results show that a realistic 4-C MEG/EEG model can be implemented using standard tools and basic BEM, without excessive workload or computational burden. If the CSF is omitted, compensated skull conductivity should be used in EEG.

  18. Analysis of clinical features, serologic and cerebrospinal fluid tests in patients with neurosyphilis at different stages

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    Bao-jie WANG

    2016-08-01

    Full Text Available Objective To summarize the clinical features, serologic, cerebrospinal fluid (CSF tests in patients with neurosyphilis at different stages.  Methods A retrospective analysis was made on the clinical features, imaging, serologic and CSF tests, treatment and prognosis of 12 cases diagnosed as neurosyphilis. In those cases, 5 cases were early-stage neurosyphilis, including 4 syphilitic meningitis (meningomyelitis and one meningovascular syphilis; 7 cases were late-stage neurosyphilis, all of whom were general paresis.  Results The serum Treponema pallidum antibody (TP-Ab and rapid plasma regain (RPR tests were positive in all 12 cases. The CSF TP-Ab tests of 12 cases were all positive and CSF RPR tests were positive in 9 cases. In 5 cases of early-stage neurosyphilis, one case had elevated intracranial pressure (ICP, 3 cases presented with elevated white blood cell (WBC, 4 cases had elevated protein concentration. In 7 cases of late-stage neurosyphilis, one case had elevated ICP, 7 cases presented with elevated WBC and protein concentration. CSF cytology showed lymphocyte reaction, mainly small lymphocytes. All cases were treated with different doses of intravenous penicillin or ceftriaxone sodium by intramuscular injection, among whom 8 cases presented improved neuropsychiatric symptoms, while 4 cases had no significant improvement.  Conclusions Neurosyphilis is easy to be misdiagnosed because of various styles of onset and nontypical clinical manifestations. A definite diagnosis depends on clinical manifestations and serologic and CSF examinations. Early diagnosis and standard treatment is essential for improving prognosis and reducing complications. DOI: 10.3969/j.issn.1672-6731.2016.07.005

  19. Clinic-Based Validation of Cerebrospinal Fluid Biomarkers with Florbetapir PET for Diagnosis of Dementia.

    Science.gov (United States)

    Álvarez, Ignacio; Aguilar, Miquel; González, Jose Manuel; Ysamat, Montse; Lorenzo-Bosquet, Carles; Alonso, Alvaro; Tartari, Juan Pablo; Romero, Silvia; Diez-Fairen, Monica; Carcel, Maria; Pujalte, Francisco; Pastor, Pau

    2018-01-01

    Cerebrospinal fluid (CSF) biomarker studies have shown variable accuracy for diagnosis of Alzheimer's disease (AD); therefore, internal validation is recommended. To investigate the correlation between CSF biomarkers and cerebral 18-Florbetapir positron emission tomography (Amyloid-PET) and calculate their sensitivity and specificity to obtain the optimal clinical cut-off points to diagnose the etiology of cognitive impairment. We performed Amyloid-PET scans and CSF biomarker levels analyses in 68 subjects (50 with mild cognitive impairment, 11 with AD dementia, and 7 with non-AD dementia). Visual examination of Amyloid-PET scans was performed. CSF analyses were performed using standard sandwich ELISA. Amyloid-PET was positive in 36 subjects, negative in 26, and inconclusive in 6. Optimal clinical cut-off points for CSF markers were the following: amyloid-β 1-42 (Aβ42) = 629 pg/ml, total tau (t-tau) = 532 pg/ml, phosphorylated tau (p-tau) = 88 pg/ml, and t-tau/Aβ42 ratio = 0.58. T-tau/Aβ42 ratio showed the best sensitivity and specificity (92 and 84%, respectively). T-tau and p-tau CSF levels (r2 = 0.867) followed by the t-tau and t-tau/Aβ42 CSF ratio (r2 = 0.666) showed the strongest inter-marker correlation. Interestingly, subjects with inconclusive Amyloid-PET showed intermediate values for all CSF markers between negative and positive Amyloid-PET groups. CSF t-tau/Aβ42 ratio appears to be the most accurate AD CSF marker. The presence of intermediate values for CSF markers among the subjects with inconclusive Amyloid-PET suggests the presence of other dementias associated with AD pathology or intermediate phenotypes.

  20. Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients.

    Science.gov (United States)

    Di Domenico, Fabio; Pupo, Gilda; Giraldo, Esther; Badìa, Mari-Carmen; Monllor, Paloma; Lloret, Ana; Schininà, Maria Eugenia; Giorgi, Alessandra; Cini, Chiara; Tramutola, Antonella; Butterfield, D Allan; Viña, José; Perluigi, Marzia

    2016-02-01

    Several studies suggest that pathological changes in Alzheimer's disease (AD) brain begin around 10-20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level. This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from subjects with AD and amnestic mild cognitive impairment (aMCI). A targeted proteomics approach has been employed to discover novel CSF biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers. CSF samples from aMCI, AD and control individuals (CTR) were collected and analyzed using a combined redox proteomics approach to identify the specific oxidatively modified proteins in AD and aMCI compared with controls. The majority of carbonylated proteins identified by redox proteomics are found early in the progression of AD, i.e., oxidatively modified CSF proteins were already present in aMCI compared with controls and remain oxidized in AD, thus suggesting that dysfunction of selected proteins initiate many years before severe dementia is diagnosed. The above findings highlight the presence of early oxidative damage in aMCI before clinical dementia of AD is manifested. The identification of early markers of AD that may be detected peripherally may open new prospective for biomarker studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite OSI-420.

    Science.gov (United States)

    Broniscer, Alberto; Panetta, John C; O'Shaughnessy, Melinda; Fraga, Charles; Bai, Feng; Krasin, Matthew J; Gajjar, Amar; Stewart, Clinton F

    2007-03-01

    To report cerebrospinal fluid (CSF) penetration of erlotinib and its metabolite OSI-420. Pharmacokinetic measurements were done in plasma (days 1, 2, 3, and 8 of therapy) and, concurrently, in plasma and CSF (before and at 1, 2, 4, 8, and 24 h after dose on day 34 of therapy) in an 8-year-old patient diagnosed with glioblastoma who received local irradiation and oral erlotinib in a phase I protocol. CSF samples were collected from a ventriculoperitoneal shunt, which was externalized because of infection. Erlotinib concentrations were determined by liquid chromatography/mass spectrometry. CSF penetration of erlotinib and OSI-420 were estimated by a compartmental model and by calculating the ratio of CSF to plasma 24-h area under concentration-time curve (AUC(0-24)). This patient was assigned to receive erlotinib at a dose level of 70 mg/m(2), but the actual daily dose was 75 mg (78 mg/m(2)). Erlotinib and OSI-420 plasma pharmacokinetic variables on days 8 and 34 overlapped to suggest that steady state had been reached. Whereas erlotinib and OSI-420 AUC(0-24) in plasma on day 34 were 30,365 and 2,527 ng h/mL, respectively, the correspondent AUC(0-24) in the CSF were 2,129 and 240 ng h/mL, respectively. Erlotinib and OSI-420 CSF penetration were 7% and approximately 9%, respectively, using both estimate methods. The maximum steady-state CSF concentration of erlotinib was approximately 130 ng/mL (325 nmol/L). The plasma pharmacokinetics of erlotinib in this child overlapped with results described in adults. Oral administration of erlotinib achieves CSF concentrations comparable with those active against several cancer cell lines in preclinical models.

  2. Neoplastic meningitis: a retrospective review of clinical presentations, radiological and cerebrospinal fluid findings.

    Science.gov (United States)

    Jearanaisilp, Sorrawit; Sangruji, Tumthip; Danchaivijitr, Chotipat; Danchaivijitr, Nasuda

    2014-08-01

    To review the clinical, radiological, and laboratory presentations of patients with neoplastic meningitis. Patients with neoplastic meningitis were recruited by a retrospective search of cerebrospinal fluid (CSF) cytopathological report database of Siriraj Hospital between 1997 and 2006. Clinical information and CSF result of these patients were extracted from their medical records. Neuroimagings were reviewed by a neuroradiologist. The present study revealed 40 cases of neoplastic meningitis, which comprised of 17 cases with carcinomatous meningitis (CM) and 23 lymphoma/leukemia meningitis (LM) cases. In patients with CM, the majority (70%) had adenocarcinoma of lung or breast. Three of 17 cases with unknown primary tumor had carcinomatous meningitis as an initial presentation. In LM most of the cases (70%) were diagnosed with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The most common symptom among patients with CM and LM was headache follow by cranial nerve palsy. In CM cases, CSF cytology was positive in the first specimen in 15 cases (82.35%) and in 22 from 23 cases (95.7%) in LM cases. Overall CSF showed pleocytosis in 36 cases (90%), most of which were lymphocyte predominant. The most common findings from brain imagings were leptomeningeal enhancement and hydrocephalus. The common primary sites were lung and breast cancer in the CM group and ALL and NHL in the LM group. The common symptoms were headache and cranial nerve palsy. Routine CSF examination was abnormal in virtually all cases. Positive CSF cytology was a gold standard for a diagnosis of leptomeningeal metastasis. High index of suspicious and awareness were required to avoid miss diagnosis.

  3. Early lead exposure increases the leakage of the blood–cerebrospinal fluid barrier, in vitro

    Science.gov (United States)

    Shi, Lewis Zhichang; Zheng, Wei

    2014-01-01

    The cell type blood–brain barrier (BBB) and blood–cerebrospinal fluid barrier (BCB) is entirely different, ie, endothelia in BBB and epithelia in BCB. Nonetheless, both barriers share a common character – the tight junctions (TJ) between adjacent cells. This study investigated the consequence of lead (Pb) exposure on the tightness of BCB. In an in vitro BCB transwell model, using immortalized choroidal epithelial Z310 cells, we found that early exposure to Pb (prior to the formation of tight barrier) at 5 and 10 μM, significantly reduced the tightness of BCB, as evidenced by a 20% reduction in transepithelial electrical resistance (TEER) values (P 20% increase in the paracellular permeability of [14C]sucrose (P < 0.05). Exposure to Pb after the formation of tight barrier, however, did not cause any detectable barrier dysfunction. RT-PCR and Western blot analyses on typical TJ proteins revealed that Pb exposure decreased both the mRNA and protein levels of claudin-1, with the membrane-bound claudin-1 more profoundly affected than cytosolic claudin-1. Pb exposure, however, had no significant effect on ZO1 and occludin. These data suggest that Pb exposure selectively alters the cellular level of claudin-1, which, in turn, reduces the tightness and augments the permeability of tight blood–CSF barrier. The immature barrier appears to be more vulnerable to Pb toxicity than the mature, well-developed, brain barrier, the fact possibly contributing to Pb-induced neurotoxicity among young children. PMID:17439918

  4. Cerebrospinal fluid procalcitonin as a biomarker of bacterial meningitis in neonates.

    Science.gov (United States)

    Reshi, Z; Nazir, M; Wani, W; Malik, M; Iqbal, J; Wajid, S

    2017-08-01

    The objective of the study was to study the performance of cerebrospinal fluid (CSF) procalcitonin as a marker for bacterial meningitis in neonates, and to determine its optimal 'cutoff' in CSF that can be called significant for the diagnosis. Neonates qualifying for lumbar puncture were prospectively studied. Procalcitonin and established CSF parameters were recorded. At a cut-off value of 0.33 ng ml -1 , CSF procalcitonin had a sensitivity of 0.92, specificity of 0.87, with positive and negative likelihood ratios of 7.13 and 0.092, respectively. The area under the curve for different CSF parameters was: 0.926 (0.887 to 0.964) (P<0.001) for procalcitonin, 0.965 (0.956 to 0.974) for total leukocyte count, 0.961 (0.94 to 0.983) for neutrophil count, 0.874 (0.825 to 0.923) for protein, 0.946 (0.914 to 0.978) for sugar and 0.92 (0.955 to 0.992) for CSF:serum sugar ratio. The lumbar puncture was traumatic in 36 (21.4%) patients; out of these 15 (41.7%) had bacterial meningitis and 21 (58.3%) had no meningitis. In traumatic lumbar tap group, the median (IQR) CSF procalcitonin in patients with and without meningitis was 1.41 (0.32-3.42) ng/ml and 0.21(0.20-0.31) ng/ml respectively (p<0.05). Procalcitonin measurement has diagnostic efficiency similar to the established CSF markers. Routine assessment of procalcitonin in clean non-contaminated CSF may not yield additional information, but it may have clinical utility in situations where diagnosis of meningitis is in dilemma, as in the case of blood contamination of CSF in traumatic lumbar punctures.

  5. USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS.

    Science.gov (United States)

    Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

    2017-01-01

    To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

  6. Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients

    Science.gov (United States)

    2013-01-01

    Background Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. Methods Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann–Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. Results Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. Conclusions Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. Trial registration The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. Registration number: NCT00497978. Local ethical protocol number: NL16222.094.07. PMID:24093540

  7. Analytical solution for pulsatile viscous flow in a straight elliptic annulus and application to the motion of the cerebrospinal fluid

    Science.gov (United States)

    Gupta, Sumeet; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2008-09-01

    We present here the analytical solution of transient, laminar, viscous flow of an incompressible, Newtonian fluid driven by a harmonically oscillating pressure gradient in a straight elliptic annulus. The analytical formulation is based on the exact solution of the governing fluid flow equations known as Navier-Stokes equations. We validate the analytical solution using a finite-volume computational fluid dynamics approach. As the analytical solution includes Mathieu and modified Mathieu functions, we also present a stepwise procedure for their evaluation for large complex arguments typically associated with viscous flows. We further outline the procedure for evaluating the associated Fourier coefficients and their eigenvalues. We finally apply the analytical solution to investigate the cerebrospinal fluid flow in the human spinal cavity, which features a shape similar to an elliptic annulus.

  8. Cerebrospinal Fluid, MRI, and Florbetaben-PET in Cerebral Amyloid Angiopathy-Related Inflammation.

    Science.gov (United States)

    Renard, Dimitri; Collombier, Laurent; Demattei, Christophe; Wacongne, Anne; Charif, Mahmoud; Ayrignac, Xavier; Azakri, Souhayla; Gaillard, Nicolas; Boudousq, Vincent; Lehmann, Sylvain; Menjot de Champfleur, Nicolas; Thouvenot, Eric

    2018-01-01

    Cerebral amyloid angiopathy-related inflammation (CAA-ri) is associated with a cerebrospinal fluid (CSF) biomarker profile similar to that observed in CAA. Few CAA-ri patients have been studied by fibrillar amyloid-β (Aβ) imaging (using 11C-Pittsburgh compound B and 18F-florbetapir, but not 18F-florbetaben). To describe CSF biomarkers, magnetic resonance imaging (MRI), and 18F-florbetaben (FBB)-positron emission tomography (PET) changes in CAA-ri patients. CSF levels of total tau, phosphorylated tau, Aβ1-42, and Aβ1-40, MRI (cerebral microbleeds count on susceptibility-weighted imaging and semi-quantitative analysis of fluid-attenuation inversion recovery white matter hyperintensities), and FBB-PET (using both cerebellar cortex and pons to calculate standardized uptake value ratios) were analyzed in nine consecutive CAA-ri patients. A median number of 769 cerebral microbleeds/patient were counted on MRI. When using the pons as reference region, amyloid load on FBB-PET was very strongly correlated to CSF Aβ1-40 levels (rho = -0.83, p = 0.008) and moderately correlated to cerebral microbleed numbers in the occipital lobes (rho = 0.59, p = 0.001), while comparisons with other CSF biomarkers were not statistically significant (total tau, rho = -0.63, p = 0.076; phosphorylated tau, rho = -0.68, p = 0.05; Aβ1-42, rho = -0.59, p = 0.09). All correlations were weaker, and not statistically significant, when using the cerebellum as reference region. A non-significant correlation (rho = -0.50, p = 0.18) was observed between CSF Aβ1-40 levels and cerebral microbleed numbers. In CAA-ri, CSF Aβ1-40 levels correlated well with amyloid load assessed by FBB-PET when the pons was used as reference, and to a lesser degree with cerebral microbleeds count on MRI. This confirms earlier data on CSF Aβ1-40 as an in vivo marker for CAA and CAA-ri.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Cerebrospinal fluid changes after intravenous injection of gadolinium chelate: assessment by FLAIR MR imaging

    International Nuclear Information System (INIS)

    Bozzao, Alessandro; Floris, Roberto; Fasoli, Fabrizio; Simonetti, Giovanni; Fantozzi, Luigi Maria; Colonnese, Claudio

    2003-01-01

    Fluid-attenuated inversion recovery (FLAIR) sequence is currently used in clinical practice. Some reports emphasize the possibility that, in pathologic conditions, intravenous injection of gadolinium chelates may lead to an increased signal inside the cerebrospinal fluid (CSF). The aim of this study was to evaluate the presence of CSF signal changes in pathologic conditions causing blood-brain barrier disruption or neovascularization when imaging is performed after intravenous injection of gadolinium. We obtained FLAIR sequences after gadolinium injection from 33 patients affected by different intracranial pathologies and 10 control subjects. Patients were affected by ischemic stroke in the subacute phase, from 2 to 7 days from onset of symptoms (12 patients), meningiomas (8 patients), high-grade gliomas (5 patients), previous surgical procedures for intra-axial neoplasms (5 patients), and multiple sclerosis with active plaques (3 patients). Magnetic resonance imaging was performed in patients and controls using a 1.5-T magnet, using T2- and T1-weighted FLAIR sequences. The FLAIR sequence was acquired before and 1-3 h after injection of a standard dose of gadolinium. In those patients affected by ischemic lesions, FLAIR sequences were repeated the next days and 3-4 days later. The CSF signal was visually evaluated by two readers and scored from 0 to 3 depending by the degree of enhancement. The location of CSF signal changes (close to the lesion, hemispheric, or diffuse) was also considered. The CSF signal was markedly increased after 3 h from intravenous injection of gadolinium in all the patients with stroke, in those with previous surgery, and in those with high-grade gliomas whose neoplasm's surface was in contact with the subarachnoid spaces (SAS) or ventricles; a strong enhancement was also evident inside the necrotic component of the tumor. The CSF changes were more evident close to the pathology and/or in the hemisphere involved by the pathology. Moderate

  11. A Poroelastic Fluid/Structure-Interaction Model of Cerebrospinal Fluid Dynamics in the Cord With Syringomyelia and Adjacent Subarachnoid-Space Stenosis.

    Science.gov (United States)

    Bertram, C D; Heil, M

    2017-01-01

    An existing axisymmetric fluid/structure-interaction (FSI) model of the spinal cord, pia mater, subarachnoid space, and dura mater in the presence of syringomyelia and subarachnoid-space stenosis was modified to include porous solids. This allowed investigation of a hypothesis for syrinx fluid ingress from cerebrospinal fluid (CSF). Gross model deformation was unchanged by the addition of porosity, but pressure oscillated more in the syrinx and the subarachnoid space below the stenosis. The poroelastic model still exhibited elevated mean pressure in the subarachnoid space below the stenosis and in the syrinx. With realistic cord permeability, there was slight oscillatory shunt flow bypassing the stenosis via the porous tissue over the syrinx. Weak steady streaming flow occurred in a circuit involving craniocaudal flow through the stenosis and back via the syrinx. Mean syrinx volume was scarcely altered when the adjacent stenosis bisected the syrinx, but increased slightly when the syrinx was predominantly located caudal to the stenosis. The fluid content of the tissues over the syrinx oscillated, absorbing most of the radial flow seeping from the subarachnoid space so that it did not reach the syrinx. To a lesser extent, this cyclic swelling in a boundary layer of cord tissue just below the pia occurred all along the cord, representing a mechanism for exchange of interstitial fluid (ISF) and cerebrospinal fluid which could explain recent tracer findings without invoking perivascular conduits. The model demonstrates that syrinx volume increase is possible when there is subarachnoid-space stenosis and the cord and pia are permeable.

  12. Disease-related changes in the cerebrospinal fluid metabolome in amyotrophic lateral sclerosis detected by GC/TOFMS.

    Directory of Open Access Journals (Sweden)

    Anna Wuolikainen

    2011-04-01

    Full Text Available The changes in the cerebrospinal fluid (CSF metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF.Using gas chromatography coupled to mass spectrometry (GC/TOFMS and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls.The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS without superoxide dismutase-1 gene (SOD1 mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar.Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease.

  13. A RARE CASE OF SPONTANEOUS PNEUMOCEPHALUS AS A COMPLICATION OF NONTRAUMATIC CEREBROSPINAL FLUID RHINORRHEA. AN EVIDENCEBASED REVIEW

    Directory of Open Access Journals (Sweden)

    E. V. Shelesko

    2017-01-01

    Full Text Available Pneumocephalus is defined as intracranial air. Pneumaticcephaly is associated with several etiological factors, such as head injuries, surgical interventions, infections and neoplasms. On average, the incidence of posttraumatic pneumocephaly fluctuates between 0.5-1% of all skull injuries. Spontaneous pneumocephalus without cerebrospinal fluid leak is very rare. Clinical manifestations of pneumocephaly depend on the location and volume of air in the cranial cavity. The most common and described symptoms are headache, “splashing sound”, rhinorrhea and otorrhea, meningism, dysfunction of cerebrospinal nerves, epileptic seizures, collaptoid states, psychiatric symptoms. In this article we report an effective treatment of spontaneous cerebrospinal fluid leak, complicated by pneumocephaly and meningitis. A 57-year-old patient was admitted to National Scientific and Practical Center of Neurosurgery named after academician N.N. Burdenko in the department of neurotrauma in a serious condition. Medical history: One year ago the patient began to notice the flow of clear fluid from the left nasal passage, which periodically spontaneously ceased, then again recurred. Two months before admission she noticed headaches, fever, nausea, vomiting. Objective data on admission: serious condition, level of consciousness: stunning, drowsiness, lethargy. There is stiff neck. The SCT of the brain shows destructive changes in the posterior wall of the main sinus, with the presence of the exudative component in the left parts of the main sinus, the latticed labyrinth, the posterior parts of the left maxillary sinus. In the ventricular system, basal cisterns, anterior sections of the frontal lobes, the accumulation of air is determined. Under general anesthesia, the operation “Endoscopic endonasal plastic of a complex skull base defect in the region of the sphenoid sinus on the left under the control of the navigation system” was performed. There was subdural

  14. Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.

    Science.gov (United States)

    Zerr, Inga; Schmitz, Matthias; Karch, André; Villar-Piqué, Anna; Kanata, Eirini; Golanska, Ewa; Díaz-Lucena, Daniela; Karsanidou, Aikaterini; Hermann, Peter; Knipper, Tobias; Goebel, Stefan; Varges, Daniela; Sklaviadis, Theodoros; Sikorska, Beata; Liberski, Pawel P; Santana, Isabel; Ferrer, Isidro; Zetterberg, Henrik; Blennow, Kaj; Calero, Olga; Calero, Miguel; Ladogana, Anna; Sánchez-Valle, Raquel; Baldeiras, Inês; Llorens, Franc

    2018-02-03

    Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown. Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182). The highest NFL levels were detected in sCJD, followed by vascular dementia, frontotemporal dementia, dementia with Lewy bodies/Parkinson's disease dementia, Alzheimer's disease, and mild cognitive impairment. In sCJD, NFL levels correlated with cerebrospinal fluid tau and disease duration. NFL levels were able to differentiate sCJD from nonprimarily neurodegenerative neurological and psychiatric diseases (area under the curve = 0.99, 95% confidence interval: 0.99-1) and from the other diagnostic groups showing cognitive impairment/dementia of a non-CJD etiology (area under the curve = 0.90, 95% confidence interval: 0.87-0.92). Compared to nonprimarily neurodegenerative neurological and psychiatric diseases, NFL was also elevated in genetic prion diseases associated with the E200K, V210I, P102L, and D178N prion protein gene mutations. Increased NFL levels are a common feature in neurodegenerative dementias. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  15. Turnover rate of cerebrospinal fluid in female sheep: changes related to different light-dark cycles

    Directory of Open Access Journals (Sweden)

    Malpaux Benoit

    2009-08-01

    Full Text Available Abstract Background Sheep are seasonal breeders. The key factor governing seasonal changes in the reproductive activity of the ewe is increased negative feedback of estradiol at the level of the hypothalamus under long-day conditions. It has previously been demonstrated that when gonadotropin secretions are inhibited during long days, there is a higher concentration of estradiol in the cerebrospinal fluid (CSF than during short days. This suggests an involvement of the CSF and choroid plexus in the neuroendocrine regulatory loop, but the mechanisms underlying this phenomenon remain unknown. One possible explanation of this difference in hormonal content is an effect of concentration or dilution caused by variations in CSF secretion rate. The aim of this study was thus to investigate changes in the CSF turnover rate related to light-dark cycles. Methods The turnover rate of the CSF was estimated by measuring the time taken for the recovery of intraventricular pressure (IVP after removal of a moderate volume (0.5 to 2 ml of CSF (slope in mmHg/min. The turnover rate was estimated three times in the same group of sheep: during a natural period of decreasing day-length corresponding to the initial period when gonadotropin activity is stimulated (SG1, during a long-day inhibitory period (IG, and finally during a short-day stimulatory period (SG2. Results The time taken and the speed of recovery of initial IVP differed between groups: 8 min 30 sec, 0.63 ± 0.07 mmHg/min(SG1, 11 min 1 sec, 0.38 ± 0.06 mmHg/min (IG and 9 min 0 sec, 0.72 ± 0.15 mmHg/min (SG2. Time changes of IVP differed between groups (ANOVA, p p p = 0.41, but was significantly different from IG: 71.33 ± 16.59 μl/min (p = 0.016. Conclusion This study shows that the turnover rate of CSF in ewes changes according to the light-dark cycle; it is increased during short day periods and reduced in long day periods. This phenomenon could account for differences in hormonal concentrations in

  16. The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity.

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    Rodrigues, Adriane Maria; Radominski, Rosana Bento; Suplicy, Henrique de Lacerda; De Almeida, Sergio Monteiro; Niclewicz, Patricia Artigas; Boguszewski, Cesar Luiz

    2002-04-01

    The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum leptin ratio during pharmacological therapy for obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus drug therapy. The patients were randomly assigned into three study groups: group I, fenproporex 25 mg/d (n = 10); group II, sibutramine 10 mg/d (n = 10); and group III, orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of leptin were examined at baseline and 2 months after therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial body weight, and the reduction was not different among the groups. Serum leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because leptin levels adjusted for body fat did not change after treatment. CSF leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After therapy, the CSF/serum leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P obese women treated during 2 months with orlistat, whereas this ratio did not change in this period of time in obese women treated with fenproporex and sibutramine.

  17. A diagnostic scale for Alzheimer's disease based on cerebrospinal fluid biomarker profiles.

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    Lehmann, Sylvain; Dumurgier, Julien; Schraen, Susanna; Wallon, David; Blanc, Frédéric; Magnin, Eloi; Bombois, Stéphanie; Bousiges, Olivier; Campion, Dominique; Cretin, Benjamin; Delaby, Constance; Hannequin, Didier; Jung, Barbara; Hugon, Jacques; Laplanche, Jean-Louis; Miguet-Alfonsi, Carole; Peoc'h, Katell; Philippi, Nathalie; Quillard-Muraine, Muriel; Sablonnière, Bernard; Touchon, Jacques; Vercruysse, Olivier; Paquet, Claire; Pasquier, Florence; Gabelle, Audrey

    2014-01-01

    The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer's disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer's disease (AD) pathologic process. For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-β 42, tau, and p-tau(181) were tested to generate categories of patients with very low (75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included. A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale's overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent multicenter dataset of

  18. YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias.

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    Llorens, Franc; Thüne, Katrin; Tahir, Waqas; Kanata, Eirini; Diaz-Lucena, Daniela; Xanthopoulos, Konstantinos; Kovatsi, Eleni; Pleschka, Catharina; Garcia-Esparcia, Paula; Schmitz, Matthias; Ozbay, Duru; Correia, Susana; Correia, Ângela; Milosevic, Ira; Andréoletti, Olivier; Fernández-Borges, Natalia; Vorberg, Ina M; Glatzel, Markus; Sklaviadis, Theodoros; Torres, Juan Maria; Krasemann, Susanne; Sánchez-Valle, Raquel; Ferrer, Isidro; Zerr, Inga

    2017-11-10

    YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing. In the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures. YKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer's disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology. CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p  0.05, AUC = 0.71) or in DLB/Parkinson's disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations. Our results unequivocally demonstrate

  19. Evaluation of high resolution gel β(2)-transferrin for detection of cerebrospinal fluid leak.

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    McCudden, Christopher R; Senior, Brent A; Hainsworth, Shirley; Oliveira, Walter; Silverman, Lawrence M; Bruns, David E; Hammett-Stabler, Catherine A

    2013-02-01

    Cerebrospinal fluid (CSF) leaks are potentially life-threatening conditions that can be diagnosed by detection of β(2)-transferrin using protein electrophoresis. Another less commonly available test is β-trace protein quantitation using immunoassay. The objectives of this study were to evaluate a new immunofixation-based β(2)-transferrin test for detection of CSF leaks and to compare it to an existing agarose gel electrophoresis test and β-trace protein immunoassay. For method comparison, 63 consecutive samples from physician-ordered β(2)-transferrin tests were analyzed using two different electrophoresis methods, agarose gel fractionation followed by acid-violet staining, and high resolution agarose gel electrophoresis followed by β(2)-transferrin immunofixation. A subset of samples (16/63) were analyzed for β-trace protein. Results were compared against patient chart data for the presence of a CSF leak. Additional studies were performed to assess the stability, detection limit, and analytical specificity of the β(2)-transferrin immunofixation test. The β(2)-transferrin immunofixation test had a sensitivity of 100 % (40/40) and specificity of 71 % (12/17) for detection of CSF leaks. By comparison, the agarose gel test had a sensitivity of 87 % (35/40) and specificity of 94 % (16/17). β-trace protein had a sensitivity of 100 % (10/10) and specificity of 86 % (5/6). Serum and saliva could be differentiated from CSF by the β(2)-transferrin immunofixation test based on their migration patterns. However, whole blood samples appeared positive for β(2)-transferrin at a threshold of ~ 4 g/L hemoglobin. At a cut-off of 3 mg/L, β-trace protein was increased in 10/10 cases with documented CSF leak and in 1/6 patients without CSF leak. Both the new immunofixation test for β(2)-transferrin and the β-trace protein were effective at detecting CSF leaks. Users of the β(2)-transferrin immunofixation test should be cautioned against interpreting samples with blood

  20. Automated pressure-controlled cerebrospinal fluid drainage during open thoracoabdominal aortic aneurysm repair.

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    Tshomba, Yamume; Leopardi, Marco; Mascia, Daniele; Kahlberg, Andrea; Carozzo, Andrea; Magrin, Silvio; Melissano, Germano; Chiesa, Roberto

    2017-07-01

    Perioperative cerebrospinal fluid (CSF) drainage is a well-established technique for spinal cord protection during thoracoabdominal aortic aneurysm (TAAA) open repair and is usually performed using dripping chamber-based systems. A new automated device for controlled and continuous CSF drainage, designed to maintain CSF pressure around the desired set values, thus avoiding unnecessary drainage, is currently available. The aim of our study was to determine whether the use of the new LiquoGuard automated device (Möller Medical GmbH, Fulda, Germany) during TAAA open repair was safe and effective in maintaining the desired CSF pressure values and whether the incidence of complications was reduced compared with a standard catheter connected to a dripping chamber. Data of patients who underwent surgical TAAA open repair using perioperative CSF drainage at our institution between October 2012 and October 2014 were recorded. The difference in CSF pressure values between patients who underwent CSF drainage with a conventional dripping chamber-based system (manual group) and patients who underwent CSF drainage with the LiquoGuard (automated group) was measured at the beginning of the intervention (T1), 15 minutes after aortic cross-clamping (T2), just before unclamping (T3), at the end of surgery (T4), and 4 hours after the end of surgery (T5). The choice of the draining systems was randomly alternated with one-to-one rate until the last six patients consecutively treated with LiquoGuard were enrolled. Primary outcomes were occurrence of spinal cord ischemia, intracranial hemorrhage, postdural puncture headache, and in-hospital mortality. The study included 152 patients who underwent open surgical TAAA repair during the study period: 73 patients underwent CSF drainage with the traditional system and 79 with LiquoGuard. The CSF pressure values at T1 and T5 were not considerably different in the two groups. By repeated-measures analysis of variance, a significant upward

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

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    Richard J Perrin

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

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

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    Wiredu Edwin K

    2007-11-01

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

  3. Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

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    Satoshi Yoshimura

    Full Text Available BACKGROUND: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF oligoclonal IgG bands (OBs and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. METHODOLOGY: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA, and varicella zoster virus (VZV in 94 patients with MS and 367 unrelated healthy controls (HCs. We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658. PRINCIPAL FINDINGS: CSF IgG abnormality was found in 59 of 94 (62.8% MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1 1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1 0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. CONCLUSIONS: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1 1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1 0405 and H. pylori infection are positively and negatively

  4. Variations in the cerebrospinal fluid proteome following traumatic brain injury and subarachnoid hemorrhage.

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    Connor, David E; Chaitanya, Ganta V; Chittiboina, Prashant; McCarthy, Paul; Scott, L Keith; Schrott, Lisa; Minagar, Alireza; Nanda, Anil; Alexander, J Steven

    2017-09-01

    Proteomic analysis of cerebrospinal fluid (CSF) has shown great promise in identifying potential markers of injury in neurodegenerative diseases [1-13]. Here we compared CSF proteomes in healthy individuals, with patients diagnosed with traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) in order to characterize molecular biomarkers which might identify these different clinical states and describe different molecular mechanisms active in each disease state. Patients presenting to the Neurosurgery service at the Louisiana State University Hospital-Shreveport with an admitting diagnosis of TBI or SAH were prospectively enrolled. Patients undergoing CSF sampling for diagnostic procedures were also enrolled as controls. CSF aliquots were subjected to 2-dimensional gel electrophoresis (2D GE) and spot percentage densities analyzed. Increased or decreased spot expression (compared to controls) was defined in terms of in spot percentages, with spots showing consistent expression change across TBI or SAH specimens being followed up by Matrix-Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS). Polypeptide masses generated were matched to known standards using a search of the NCBI and/or GenPept databases for protein matches. Eight hundred fifteen separately identifiable polypeptide migration spots were identified on 2D GE gels. MALDI-MS successfully identified 13 of 22 selected 2D GE spots as recognizable polypeptides. Statistically significant changes were noted in the expression of fibrinogen, carbonic anhydrase-I (CA-I), peroxiredoxin-2 (Prx-2), both α and β chains of hemoglobin, serotransferrin (Tf) and N-terminal haptoglobin (Hp) in TBI and SAH specimens, as compared to controls. The greatest mean fold change among all specimens was seen in CA-I and Hp at 30.7 and -25.7, respectively. TBI specimens trended toward greater mean increases in CA-I and Prx-2 and greater mean decreases in Hp and Tf. Consistent CSF elevation of CA-I and Prx-2 with

  5. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

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    Angel, Thomas E.; Jacobs, Jon M.; Spudich, Serena S.; Gritsenko, Marina A.; Fuchs, Dietmar; Liegler, Teri; Zetterberg, Henrik; Camp, David G.; Price, Richard W.; Smith, Richard D.

    2012-03-20

    Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with

  6. Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage.

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    Ďuriš, Kamil; Neuman, Eduard; Vybíhal, Václav; Juráň, Vilém; Gottwaldová, Jana; Kýr, Michal; Vašků, Anna; Smrčka, Martin

    2018-03-01

     Subarachnoid hemorrhage (SAH) is a severe condition associated with high mortality. Early brain injury (EBI) plays an important role in the pathophysiology of SAH, and inflammation is a major contributor to EBI. Inflammation is a widely studied topic in both experimental and clinical conditions; however, just a few clinical studies have focused primarily on the early inflammatory response after SAH, and detailed information about the association between the dynamics of early inflammatory response with main clinical characteristics is lacking. This study analyzes the early dynamics of inflammatory response after SAH and evaluates the possible associations between the markers of early inflammatory response and main clinical characteristics.  A total of 47 patients with a diagnosis of aneurysmal SAH within the last 24 hours were enrolled in the study. All treatments, including treatment of aneurysm (surgery/coiling) and implantation of a drainage system (external ventricular drainage/lumbar catheter), were conducted in the same way as in other patients with this diagnosis. Blood and cerebrospinal fluid (CSF) samples were collected three times a day for 4 days. The dynamics of proinflammatory cytokines were assessed, and associations between levels of the proinflammatory cytokines interleukin (IL)-6, IL-1β, or tumor necrosis factor (TNF)α and main clinical characteristics were evaluated using linear mixed-effect models.  The CSF levels of IL-6 were massively increased initially after SAH (up to 72 hours) with an additional increase in later phases (after 72 hours), but there was high variability in IL-6 levels. A significant association was noted between the Glasgow Outcome Scale score and both overall levels of IL-6 ( p  = 0.0095) and their dynamics ( p  = 0.0208); the effect of the Hunt and Hess scale was borderline ( p  = 0.0887). No association was found between IL-6 levels and Fisher grade, modality of treatment (surgery, coiling, no treatment

  7. Carotid Atherosclerosis, Cerebrospinal Fluid Pressure, and Retinal Vessel Diameters: The Asymptomatic Polyvascular Abnormalities in Community Study.

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    Jing Yan Yang

    Full Text Available To assess relationships between carotid artery atherosclerosis and retinal arteriolar and venular diameters.The community-based longitudinal Asymptomatic Polyvascular Abnormalities Community Study (APAC included a sub-population of the Kailuan study which consisted of 101,510 employees and retirees of a coal mining industry. Based on the Chinese National Census 2010 and excluding individuals with history of cerebrovascular ischemic events, 4004 individuals were included into the APAC. All participants underwent a detailed clinical examination including blood laboratory tests and carotid artery duplex ultrasound examination. The cerebrospinal fluid pressure (CSFP was estimated using the formula: CSFP[mmHg] = 0.44xBody Mass Index[kg/m2]+0.16xDiastolic Blood Pressure[mmHg]-0.18 x Age[Years]-1.91.In multivariable analysis (goodness of fit r2:0.12, thicker retinal arteries were associated with a thinner common carotid artery intima-media thickness (IMT (P = 0.002; standardized regression coefficient beta:-0.06; non-standardized regression coefficient B:-6.92;95% confidence interval (CI:-11.2,-2.61 after adjusting for thicker retinal nerve fiber layer (P<0.001;beta:0.18;B:0.35;95%CI:0.28,0.42, lower diastolic blood pressure (P<0.001;beta:-0.16;B:-0.17;95%CI:-0.21,-0.3, younger age (P<0.001;beta:-0.08; B:-0.16;95%;CI:-0.25,-0.08, and less abdominal circumference (P = 0.003;beta:-0.06;B:-0.11;95%CI:-0.18,-0.03. Thicker retinal vein diameter was associated (r = 0.40 with higher estimated CSFP (P<0.001;beta:0.09;B:0.78;95%CI:0.47,1.08 after adjusting for wider retinal arteries (P<0.001;beta:0.27;B:0.36;95%CI:0.31,0.41, thicker retinal nerve fiber layer thickness (P = 0.03;beta:0.22;B:0.56;95%CI:0.46,0.65 and male gender (P<0.001;beta:-0.08;B:-3.98;95%CI:-5.88,2.09.Thinner retinal artery diameter was significantly, however weakly, associated with increased common carotid artery IMT. It suggests that retinal microvascular changes were only week indicators

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

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    Wilhelmina G Leen

    Full Text Available 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 reference values. In 1993 The Nijmegen Observational CSF Study was started. Results of all CSF samples that were analyzed between 1993 and 2008 at our laboratory were systematically collected and stored in our computerized database. After exclusion of CSF samples with an unknown or elevated erythrocyte count, an elevated leucocyte count, elevated concentrations of bilirubin, free hemoglobin, or total protein 9,036 CSF samples were further studied for CSF glucose (n = 8,871, CSF/plasma glucose ratio (n = 4,516 and CSF lactate values (n = 7,614. CSF glucose, CSF/plasma glucose ratio and CSF lactate were age-, but not sex dependent. Age-specific reference ranges were defined as 5-95(th percentile ranges. CSF glucose 5(th percentile values ranged from 1.8 to 2.9 mmol/L and 95(th percentile values from 3.8 to 5.6 mmol/L. CSF/plasma glucose ratio 5(th percentile values ranged from 0.41 to 0.53 and 95(th percentile values from 0.82 to 1.19. CSF lactate 5(th percentile values ranged from 0.88 to 1.41 mmol/L and 95(th percentile values from 2.00 to 2.71 mmol/L. Reference ranges for all three parameters were widest in neonates and narrowest in toddlers, with lower and upper limits increasing with age. These reference values allow a reliable interpretation of CSF results in everyday clinical practice. Furthermore, hypoglycemia was associated with an increased CSF/plasma glucose ratio, whereas hyperglycemia did not affect the CSF/plasma glucose ratio.

  9. First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid

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    Sharma CV

    2017-11-01

    Full Text Available Chhaya V Sharma,1 Jamie H Long,2 Seema Shah,1 Junia Rahman,1 David Perrett,3 Samir S Ayoub,4 Vivek Mehta1 1Pain & Anaesthesia Research Centre, St Bartholomew’s and The Royal London Hospitals, Barts Health NHS Trust, London, UK; 2Barts & The London School of Medicine, Queen Mary University of London, London, UK; 3BioAnalytical Science, Barts & The London School of Medicine, Queen Mary University of London, London, UK; 4School of Health, Sport and Bioscience, Medicines Research Group, University of East London, London, UK Abstract: Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404. AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic ­neurons, as well as inhibiting synthesis of PGE2 by COX-2. However, the presence of AM404 in the central nervous system following administration of paracetamol has not yet been demonstrated in humans. Cerebrospinal fluid (CSF and blood were collected from 26 adult male patients between 10 and 211 minutes following intravenous administration of 1 g of paracetamol. Paracetamol was measured by high-performance liquid chromatography with UV detection. AM404 was measured by liquid chromatography-tandem mass spectrometry. AM404 was detected in 17 of the 26 evaluable CSF samples at 5–40 nmol⋅L–1. Paracetamol was measurable in CSF within 10 minutes, with a maximum measured concentration of 60 μmol⋅L–1 at 206 minutes. This study is the first to report on the presence of AM404 in human CSF following paracetamol administration. This may represent an important finding in our understanding of

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

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    Okko T Pyykkö

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

  11. Drug concentrations in the serum and cerebrospinal fluid of patients treated with norvancomycin after craniotomy.

    Science.gov (United States)

    Wu, Y; Kang, J; Wang, Q

    2017-02-01

    Intracranial infection by gram-positive cocci is commonly found after craniotomy. Norvancomycin was independently developed in China, and had demonstrated therapeutic capability against gram-positive infection. This study investigated the serum and cerebrospinal fluid (CSF) concentrations in patients that received intravenous injection of norvancomycin after craniotomy. Patients with an indwelling catheter in the operational area/ventricle after craniotomy were administered norvancomycin by two approaches: (1) The conventional group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, every 12 h; (2) The continuous administration group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, and then another 0.4 g for 11 h with extended infusion, followed by continuous infusion of 0.4 g norvancomycin for 12 h. Samples of serum and CSF were collected at different time-points to measure norvancomycin levels after administration. In the conventional and continuous administration groups, the peak serum concentrations of norvancomycin were 55.52 ± 26.04 and 59.22 ± 41.88 mg/L, respectively, while those at 24 h were 8.21 ± 6.04 and 8.01 ± 4.17 mg/L, respectively. Meanwhile, peak CSF concentrations were 16.31 ± 11.15 and 8.82 ± 8.91 mg/L, respectively, while those at 24 h were 6.12 ± 2.34 and 6.24 ± 4.38 mg/L, respectively. This preliminary study showed that for the early administration of standard doses of norvancomycin post-neurosurgery, the CSF concentration in both the conventional and continuous administration groups reached or exceeded the 90 % minimum inhibitory concentration (MIC 90 , 2 mg/L) of target bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).

  12. Diagnostic Accuracy of Cerebrospinal Fluid Procalcitonin in Bacterial Meningitis Patients with Empiric Antibiotic Pretreatment.

    Science.gov (United States)

    Li, Wen; Sun, Xiaolong; Yuan, Fang; Gao, Qiong; Ma, Yue; Jiang, Yongli; Yang, Xiai; Yang, Fang; Ma, Lei; Jiang, Wen

    2017-04-01

    Accurate diagnosis of bacterial meningitis (BM) relies on cerebrospinal fluid (CSF) Gram staining and bacterial culture, which often present high false-negative rates because of antibiotic abuse. Thus, a novel and reliable diagnostic biomarker is required. Procalcitonin (PCT) has been well demonstrated to be specifically produced from peripheral tissues by bacterial infection, which makes it a potential diagnostic biomarker candidate. Here, we performed a prospective clinical study comprising a total of 143 patients to investigate the diagnostic value of CSF PCT, serum PCT, and other conventional biomarkers for BM. Patients were assigned to the BM ( n = 49), tuberculous meningitis (TBM) ( n = 25), viral meningitis/encephalitis (VM/E) ( n = 34), autoimmune encephalitis (AIE) ( n = 15), or noninflammatory nervous system diseases (NINSD) group ( n = 20). Empirical antibiotic pretreatment was not an exclusion criterion. Our results show that the CSF PCT level was significantly ( P < 0.01) higher in patients with BM (median, 0.22 ng/ml; range, 0.13 to 0.54 ng/ml) than in those with TBM (median, 0.12 ng/ml; range, 0.07 to 0.16 ng/ml), VM/E (median, 0.09 ng/ml; range, 0.07 to 0.11 ng/ml), AIE (median, 0.06 ng/ml; range, 0.05 to 0.10 ng/ml), or NINSD (median, 0.07 ng/ml; range, 0.06 to 0.08 ng/ml). Among the assessed biomarkers, CSF PCT exhibited the largest area under the receiver operating characteristic curve (0.881; 95% confidence interval, 0.810 to 0.932; cutoff value, 0.15 ng/ml; sensitivity, 69.39%; specificity, 91.49%). Our study sheds light upon the diagnostic dilemma of BM due to antibiotic abuse. (This study has been registered at ClinicalTrials.gov under registration no. NCT02278016.). Copyright © 2017 American Society for Microbiology.

  13. Genomic Comparison of Escherichia coli K1 Strains Isolated from the Cerebrospinal Fluid of Patients with Meningitis †

    OpenAIRE

    Yao, Yufeng; Xie, Yi; Kim, Kwang Sik

    2006-01-01

    Escherichia coli is a major cause of enteric/diarrheal diseases, urinary tract infections, and sepsis. E. coli K1 is the leading gram-negative organism causing neonatal meningitis, but the microbial basis of E. coli K1 meningitis is incompletely understood. Here we employed comparative genomic hybridization to investigate 11 strains of E. coli K1 isolated from the cerebrospinal fluid (CSF) of patients with meningitis. These 11 strains cover the majority of common O serotypes in E. coli K1 iso...

  14. Increased prevalence of lymphoid tissue inducer cells in the cerebrospinal fluid of patients with early multiple sclerosis

    DEFF Research Database (Denmark)

    Degn, Matilda; Modvig, Signe; Dyring-Andersen, Beatrice

    2016-01-01

    BACKGROUND: Inflammatory cytokines produced by cells of the immune system are believed to play a central role in the pathogenesis of multiple sclerosis (MS). Innate lymphoid cells (ILCs) have been shown to produce and secrete a wide range of the cytokines involved in MS pathogenesis; however...... in the cerebrospinal fluid (CSF) of patients experiencing their first or second demyelinating event. We found a substantial increase in both frequency and number of ILCs, in particular the LTi subset, as compared to healthy controls. We also found an association between CSF pleocytosis and an increased frequency...

  15. Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer’s Disease in Clinical Practice: An Illustration with 3 Case Reports

    Directory of Open Access Journals (Sweden)

    Diane Slats

    2010-02-01

    Full Text Available Analysis of the brain specific biomarkers amyloid β42 (Aβ42 and total tau (t-tau protein in cerebrospinal fluid (CSF has a sensitivity and specificity of more than 85% for differentiating Alzheimer’s Disease (AD from non-demented controls. International guidelines are contradictory in their advice on the use of CSF biomarkers in AD diagnostics, resulting in a lack of consistency in clinical practice. We present three case reports that illustrate clinical practice according to the Dutch and European guidelines and portray the value of CSF biomarker analysis as an add-on diagnostic to the standard diagnostic workup for AD.

  16. Post-traumatic cerebrospinal fluid fistula: a case report; Fistula liquorica pos-traumatica - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Tamburus, Wander Miguel; Figueiredo Wanderley, Eliana Christina; Maciel, Damacio Ramon Kaimen; Narciso, Avelino Jose Soares; Sendenski, Mauricio Michalak [Universidade Estadual de Londrina, PR (Brazil). Centro de Ciencias da Saude

    1996-10-01

    Fronto-basal fracture occurs in around 5% of cranioencephalic trauma. the involved structures are: arachnoid, dura-mater, osseous base and the mucosa, and there us contact between the brain and the environment. Even with rupture of all these structures cerebrospinal fluid leakage may not occur; regardless of this, there may be infectious complications, such as bacterial meningitis or brain abscess. the authors report the case of a patient with head injury and four bacterial meningitis, the diagnosis of post-traumatic liquoric fistula being made only through magnetic resonance imaging. (author) 10 refs., 1 fig.

  17. Comparison of BacT/Alert FAN and FAN Plus Bottles with Conventional Medium for Culturing Cerebrospinal Fluid.

    Science.gov (United States)

    Yoo, In Young; Chun, Sejong; Song, Dong Joon; Huh, Hee Jae; Lee, Nam Yong

    2016-11-01

    We compared the BacT/Alert system FAN and FAN Plus media to conventional media for culturing cerebrospinal fluid (CSF) with 2,545 samples. FAN/FAN Plus bottles showed better performance for isolating microorganisms in CSF than conventional media (positive rate, 7.2% [182/2,545] versus 3.1% [80/2,545]). The incremental recovery rate of Cryptococcus neoformans from FAN Plus bottles was higher than that from FAN bottles. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Elevated Surfactant Protein Levels and Increased Flow of Cerebrospinal Fluid in Cranial Magnetic Resonance Imaging.

    Science.gov (United States)

    Schob, Stefan; Weiß, Alexander; Surov, Alexey; Dieckow, Julia; Richter, Cindy; Pirlich, Mandy; Horvath-Rizea, Diana; Härtig, Wolfgang; Hoffmann, Karl-Titus; Krause, Matthias; Quäschling, Ulf

    2017-12-27

    Surfactant proteins (SPs) are a multifunctional group of proteins, responsible for the regulation of rheological properties of body fluids, host defense, and cellular waste clearance. Their concentrations are changed in cerebrospinal fluid (CSF) of patients suffering from communicating hydrocephalus. Hydrocephalic conditions are accompanied by altered CSF flow dynamics; however, the association of CSF-SP concentrations and CSF flow has not yet been investigated. Hence, the aim of this study was to evaluate the association between SP concentrations in the CSF and marked CSF flow phenomena at different anatomical landmarks of CSF spaces. Sixty-one individuals (15 healthy subjects and 46 hydrocephalus patients) were included in this study. CSF specimens were analyzed for SP-A, SP-B, SP-C, and SP-D concentrations by the use of enzyme-linked immunosorbent assays (ELISA). CSF flow was evaluated in axial T2_turbo inversion recovery magnitude (TIRM)-weighted and sagittal T2-weighted magnetic resonance imaging sections using a 4-grade scale (1-no flow, 2-subtle flow, 3-moderate flow, and 4-strong flow). CSF-SP concentrations (mean ± standard deviation) of the overall collective were as follows: SP-A = 0.73 ± 0.58 ng/ml, SP-B = 0.17 ± 0.93 ng/ml, SP-C = 0.95 ± 0.75 ng/ml, and SP-D = 7.43 ± 5.17 ng/ml. The difference between healthy controls and hydrocephalic patients regarding CSF concentrations of SP-A (0.34 ± 0.22 vs. 0.81 ± 0.59 ng/ml) and SP-C (0.48 ± 0.29 vs. 1.10 ± 0.79 ng/ml) revealed to be statistically significant as calculated by means of ANOVA (p values of 0.022 and 0.007, respectively). CSF flow voids were detectable at all investigated landmarks of the CSF spaces (foramina of Monro, third ventricle, mesencephalic aqueduct, prepontine cistern, fourth ventricle, cisterna magna, and craniocervical junction). CSF flow voids, reported as mean ± standard deviation, revealed to be significantly increased

  19. Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls.

    Directory of Open Access Journals (Sweden)

    Pierre de Flon

    Full Text Available To investigate changes in the cerebrospinal fluid (CSF immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS, and to compare the profile in MS patients with healthy controls (HC.Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10, IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8 decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

  20. Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: comparison of primer sets for Cryptococcus neoformans and Cryptococcus gattii species complex.

    Science.gov (United States)

    Martins, Marilena dos Anjos; Brighente, Kate Bastos Santos; Matos, Terezinha Aparecida de; Vidal, Jose Ernesto; Hipólito, Daise Damaris Carnietto de; Pereira-Chioccola, Vera Lucia

    2015-01-01

    This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cerebrospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.