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PubMed Central

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

Whedon, James M.; Glassey, Donald



Cerebrospinal fluid pressure1  

Microsoft Academic Search

The cerebrospinal fluid pressure at the foramen of Monro in man in the recumbent position is less than 100 mm water relative to atmospheric pressure. The oscillations in the pressure wave due to respiration and cardiac pulsation vary with the actual pressure and increase as the overall pressure rises. In man lying horizontally the oscillation at the foramen of Monro

K. C. Bradley



Cerebrospinal Fluid Shunts  

Microsoft Academic Search

Hydrocephalus is a congenital or acquired condition in which cerebrospinal fluid (CSF) accumulates in the ventricles and the\\u000a subarachnoid space around the brain (Fig. 1). It can lead to an increase in intracranial pressure. It has existed since primitive\\u000a man roamed the earth. Man’s understanding of anatomy and physiology has often consisted mainly of myth and superstition. The\\u000a earliest recording

Edward Rustamzadeh; Cornelius H. Lam


Microscopic examinations of human cerebrospinal fluid (CSF)  

NASA Astrophysics Data System (ADS)

The increase in inception rate connected with the cerebrospinal fluid have been observed recently. In the cerebrospinal fluid there are various types of suspension. There are cells and proteins which form different dispersion systems of given the sizes and concentrations among them. Finding out the physical processes occurring in the human cerebrospinal fluid is a problem of high importance. Coagulation, coalescence, aggregation and other physical processes in the cerebrospinal fluid depend on the state of health of the person who the sample was taken from. Thus it influences the concentration of suspension, its type and the sizes of suspended particles as well. In the paper the authors present the results of examinations of suspension in non-coloured human cerebrospinal fluid and the preliminary analysis of concentration of suspension and the sizes of suspended particles. The results were obtained by microscoping.

Staro?, Waldemar; Herbowski, Leszek; Gurgul, Henryk



Low cerebrospinal fluid pressure headache  

Microsoft Academic Search

Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Alterations in cerebrospinal fluid (CSF) pressure lead to neurologic symptoms, the most common clinical manifestation of which\\u000a is headache. Typically, the headache is orthostatic and related to traction on pain-sensitive intracranial and meningeal structures,\\u000a distention on periventricular pain-sensitive areas, and direct pressure on pain conveying cranial nerves.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Low CSF headache is a distinct and familiar syndrome

Christine M. Lay



Regulation of Adipogenesis by Lymphatic Fluid Stasis Part I: Adipogenesis, Fibrosis, and Inflammation  

PubMed Central

Background Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goals of this two-part study were to determine the effect of lymphatic fluid stasis on adipogenesis and inflammation (part 1) and how these changes regulate the temporal and spatial expression of fat differentiation genes (part 2). Methods Adult female mice underwent tail lymphatic ablation and were sacrificed 6 weeks after surgery (n=20). Fat deposition, fibrosis, and inflammation were then analyzed in the regions of the tail exposed to lymphatic fluid stasis as compared with normal lymphatic flow. Results Lymphatic fluid stasis in the tail resulted in significant subcutaneous fat deposition with a 2-fold increase in fat thickness (p<0.01). In addition, lymphatic stasis was associated with subcutaneous fat fibrosis and collagen deposition. Adipogenesis in response to lymphatic fluid stasis was associated with a marked mononuclear cell inflammatory response (5-fold increase in CD45+ cells; p<0.001). In addition, we noted a significant increase in the number of monocytes/macrophages as identified by F4/80 immunohistochemistry (p<0.001). Conclusions The mouse-tail model has pathological findings that are similar to clinical lymphedema including fat deposition, fibrosis, and inflammation. Adipogenesis in response to lymphatic fluid stasis closely resembles this process in obesity. This model therefore provides an excellent means to study the molecular mechanisms that regulate the pathophysiology of lymphedema.

Zampell, Jamie C.; Aschen, Seth; Weitman, Evan S.; Yan, Alan; Elhadad, Sonia; De Brot Andrade, Marina; Mehrara, Babak J.



An Investigation of Cerebrospinal Fluid Shunt Valves.  

National Technical Information Service (NTIS)

The report represents the results of phase II of an investigation involving the development and evaluation of tests which can be used to demonstrate that a given Cerebrospinal Fluid (CSF) Shunt Valve will perform its intended regulating function. Included...

H. D. Keith X. Avula C. Schelich C. Watts



Low Cerebrospinal Fluid Pressure Headache.  


Alterations in cerebrospinal fluid (CSF) pressure lead to neurologic symptoms, the most common clinical manifestation of which is headache. Typically, the headache is orthostatic and related to traction on pain-sensitive intracranial and meningeal structures, distention on periventricular pain-sensitive areas, and direct pressure on pain conveying cranial nerves. Low CSF headache is a distinct and familiar syndrome that is seen most frequently following lumbar puncture. In this clinical scenario, the diagnosis and proposed plan of treatment are obvious. Over the past decade, however, an emerging syndrome of spontaneous intracranial hypotension (SIH) is being recognized with increasing frequency. Most of these patients are found to have spontaneous CSF leaks and have unique, clinically distinct imaging findings, which confirm the diagnosis leading to appropriate treatment. Spontaneous intracranial hypotension is a relatively benign and usually self-limiting syndrome of orthostatic headache in association with one or more of numerous symptoms including nausea, vomiting, horizontal diplopia, unsteadiness or vertigo, altered hearing, neck pain/stiffness, interscapular pain, and occasionally visual field cuts. The headache itself, while often orthostatic, may initially be non-positional, may lose its orthostatic features, or rarely or never be orthostatic. It may be gradual, subacute, or thunderclap in onset. There may be a history of minor, antecedent trauma. By very definition, the opening CSF pressure is low, below 60 mm H(2)O, and often a "dry" tap is encountered. However, the pressure may be normal, especially with intermittent leaks and may vary tap to tap. Fluid analysis is normal. Brain (and occasionally spinal) MRI studies, with gadolinium enhancement should be undertaken. In patients with SIH, studies typically reveal diffuse pachymeningeal enhancement, frequently in association with "sagging"of the brain, tonsilar descent, and posterior fossa crowding. Spinal MRI is an up and coming investigational technique, which may be helpful even in the case of a normal brain MRI. Computed tomography myelography is the diagnostic study of choice and may follow radiocisternography, which often shows absence of activity over the convexities and early appearance of activity in the renal/urinary tract. Although conservative measures are often undertaken first, epidural blood patch (EBP) is the treatment of choice. For those who fail EBP, surgery may need to be undertaken in those cases with clearly identified leaks. PMID:12162924

Lay, Christine M.



Pharmacokinetics and Cerebrospinal Fluid Concentration of Nafcillin in Pediatric Patients Undergoing Cerebrospinal Fluid Shunt Placement  

Microsoft Academic Search

Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but no pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 ± 5.6 years) received three doses of

Milap C. Nahata; Patty Fan-Havard; Edward J. Kosnik; Henry Bartkowski; William J. Barson



Paradoxical Postural Headaches in Cerebrospinal Fluid Leaks  

Microsoft Academic Search

Two patients with cerebrospinal fluid (CSF) leak, one at the level of fourth thoracic spine and another with undetermined level of leak, presented with paradoxical postural headaches in that the headaches were present when in a horizontal position and resolved if the patients were upright. One patient improved spontaneously and the other responded to a targeted epidural blood patch. Paradoxical

B Mokri; A J Aksamit; J LD Atkinson



Neuroactive steroids in periphery and cerebrospinal fluid  

Microsoft Academic Search

Some peripheral steroids penetrate the blood-brain barrier (BBB), providing at least substances for the CNS steroid metabolome. That is why the predictive value of the peripheral steroids appears to be comparable with that of the cerebrospinal fluid (CSF) steroids. The concentrations of the CSF steroids are pronouncedly lower in comparison with the ones in circulation. The available data indicate that

R. Kancheva; M. Hill; Z. Novák; J. Chrastina; L. Kancheva; L. Stárka



Human neuroglobin protein in cerebrospinal fluid  

Microsoft Academic Search

BACKGROUND: Neuroglobin is a hexacoordinated member of the globin family of proteins. It is predominantly localized to various brain regions and retina where it may play a role in protection against ischemia and nitric oxide-induced neural injury. Cerebrospinal fluid was collected from 12 chronic regional or systemic pain and 5 control subjects. Proteins were precipitated by addition of 50% 0.2

Begona Casado; Lewis K Pannell; Gail Whalen; Daniel J Clauw; James N Baraniuk



Cerebrospinal Fluid Shunt Infection by Neisseria sicca  

Microsoft Academic Search

Neisseria sicca is considered to be a nonpathogenic oral saprophyte. Presented here is an unusual case of cerebrospinal fluid (CSF) shunt infection by N. sicca. Although medical management of the common community-acquired meningitides, including infection by Neisseria meningitidis, is often successful in patients with CSF shunts, removal and replacement of the infected shunt was necessary in this case.

Galina Hornyik



Tegmental Defects and Cerebrospinal Fluid Otorrhea  

Microsoft Academic Search

Congenital tegmental defects that present as unsuspected cerebrospinal fluid (CSF) otorrhea are diagnostic and therapeutic challenges. We reviewed 5 such patients to determine an optimal strategy for evaluation. Five patients presented with watery otorrhea, 4 of them after ventilation tube placement, and only 1 with rhinorrhea. The preoperative analysis of middle ear effusion for ?2-transferrin was positive in 2\\/4, equivocal

Hannu J. Valtonen; Carl A. Geyer; Edward C. Tarlov; Carl B. Heilman; Dennis S. Poe



Cerebrospinal fluid may mediate CNS ischemic injury  

Microsoft Academic Search

BACKGROUND: The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. METHODS: Lumbar spinal cord ischemia

Yanming F Wang; Judith K Gwathmey; Guorong Zhang; Sulpicio G Soriano; Shunli He; Yanguang Wang



The Treatment of Cerebrospinal Fluid Shunt Infections  

Microsoft Academic Search

It is our impression that the management strategy for infected cerebrospinal fluid (CSF) shunts varies significantly among pediatric neurosurgeons. The purpose of this paper is to present the results of a practice survey on the treatment of shunt infections which was distributed to all active members of the American Society of Pediatric Neurosurgeons (ASPN). Eighty-four of 129 ASPN members (65%)

William E. Whitehead; John R. W. Kestle



Regulation of Adipogenesis by Lymphatic fluid Stasis Part II: Expression of Adipose Differentiation Genes  

PubMed Central

Background Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goal of this study was to determine how lymphatic fluid stasis regulates adipogenic gene activation and fat deposition. Methods Adult female mice underwent tail lymphatic ablation and sacrifice at 1, 3, or 6 weeks post-operatively (n=8/group). Samples were analyzed by immunohistochemistry and western blot. An alternative group of mice underwent axillary dissections or sham incisions and limb tissues were harvested 3 weeks post-operatively (n=8/group). Results Lymphatic fluid stasis resulted in significant subcutaneous fat deposition and fibrosis in lymphedematous tail regions (p<0.001). Western blot analysis demonstrated that proteins regulating adipose differentiation including CCAAT/enhancer binding protein-alpha (CEBP-?) and adiponectin were markedly upregulated in response to lymphatic fluid stasis in the tail and axillary models. Expression of these markers increased in edematous tissues according to the gradient of lymphatic stasis distal to the wound. Immunohistochemical analysis further demonstrated that adiponectin and peroxisome proliferator-activated receptor gamma (PPAR-?), another critical adipogenic transcription factor, followed similar expression gradients. Finally, adiponectin and PPAR-? expression localized to a variety of cell types in newly formed subcutaneous fat. Conclusions The mouse-tail model of lymphedema demonstrates pathological findings similar to clinical lymphedema including fat deposition and fibrosis. We show that lymphatic fluid stasis potently upregulates the expression of fat differentiation markers both spatially and temporally. These studies elucidate mechanisms regulating abnormal fat deposition in lymphedema pathogenesis and therefore provide a basis for developing targeted treatments.

Aschen, Seth; Zampell, Jamie C.; Elhadad, Sonia; Weitman, Evan; De Brot Andrade, Marina; Mehrara, Babak J.



Cerebrospinal fluid secretion by the choroid plexus.  


The choroid plexus epithelium is a cuboidal cell monolayer, which produces the majority of the cerebrospinal fluid. The concerted action of a variety of integral membrane proteins mediates the transepithelial movement of solutes and water across the epithelium. Secretion by the choroid plexus is characterized by an extremely high rate and by the unusual cellular polarization of well-known epithelial transport proteins. This review focuses on the specific ion and water transport by the choroid plexus cells, and then attempts to integrate the action of specific transport proteins to formulate a model of cerebrospinal fluid secretion. Significant emphasis is placed on the concept of isotonic fluid transport across epithelia, as there is still surprisingly little consensus on the basic biophysics of this phenomenon. The role of the choroid plexus in the regulation of fluid and electrolyte balance in the central nervous system is discussed, and choroid plexus dysfunctions are described in a very diverse set of clinical conditions such as aging, Alzheimer's disease, brain edema, neoplasms, and hydrocephalus. Although the choroid plexus may only have an indirect influence on the pathogenesis of these conditions, the ability to modify epithelial function may be an important component of future therapies. PMID:24137023

Damkier, Helle H; Brown, Peter D; Praetorius, Jeppe



Spontaneous cerebrospinal fluid leak syndrome: report of 18 cases  

Microsoft Academic Search

We examined a group of 18 consecutive patients with spontaneous cerebrospinal fluid leak syndrome (SCSFLS) and investigated clinical, MRI, radioisotope findings and therapeutic outcome of this syndrome.

E. Ferrante; R. Wetzl; A. Savino; A. Citterio; A. Protti



Cerebrospinal fluid lactic acidosis in bacterial meningitis.  

PubMed Central

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.

Eross, J; Silink, M; Dorman, D



Stasis Ulcer  


newsletter | contact Share | Stasis Ulcer Information for adults A A A This image displays a patient with chronic leg swelling with stasis dermatitis and a stasis ulcer. Overview A stasis ulcer is a breakdown of ...


Drug transport in brain via the cerebrospinal fluid  

PubMed Central

The human brain has no lymphatic system, but produces over a half-liter each day of cerebrospinal fluid. The cerebrospinal fluid is secreted at the choroid plexus and occupies the cavities of the four ventricles, as well as the cranial and spinal sub-arachnoid space. The cerebrospinal fluid moves over the surfaces of the brain and spinal cord and is rapidly absorbed into the general circulation. The choroid plexus forms the blood-cerebrospinal fluid barrier, and this barrier is functionally distinct from the brain microvascular endothelium, which forms the blood-brain barrier. Virtually all non-cellular substances in blood distribute into cerebrospinal fluid, and drug entry into cerebrospinal fluid is not an index of drug transport across the blood-brain barrier. Drug injected into the cerebrospinal fluid rapidly moves into the blood via bulk flow, but penetrates into brain tissue poorly owing to the limitations of diffusion. Drug transport into cerebrospinal fluid vs. brain interstitial fluid requires knowledge of the relative expression of transporters at the choroid plexus versus the brain microvascular endothelium.



Novel cyclovirus in human cerebrospinal fluid, Malawi, 2010-2011.  


To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism. PMID:23968557

Smits, Saskia L; Zijlstra, Ed E; van Hellemond, Jaap J; Schapendonk, Claudia M E; Bodewes, Rogier; Schürch, Anita C; Haagmans, Bart L; Osterhaus, Albert D M E



A chronic fatigue syndrome – related proteome in human cerebrospinal fluid  

Microsoft Academic Search

BACKGROUND: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. METHODS: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50

James N. Baraniuk; Begona Casado; Hilda Maibach; Daniel J. Clauw; Lewis K. Pannell; Sonja Hess S



Proteomic analysis of multiple sclerosis cerebrospinal fluid.  


Two-dimensional gel electrophoresis and peptide mass fingerprinting were used to identify proteins in cerebrospinal fluid (CSF) pooled from three patients with multiple sclerosis (MS) and in CSF pooled from three patients with non-MS inflammatory central nervous system (CNS) disorders. Resolution of CSF proteins on three pH gradients (3-10, 4-7 and 6-11) enabled identification of a total of 430 spots in the MS CSF proteome that represented 61 distinct proteins. The gels containing MS CSF revealed 103 protein spots that were not seen on control gels. All but four of these 103 spots were proteins known to be present in normal human CSF. The four exceptions were: CRTAC-IB (cartilage acidic protein), tetranectin (a plasminogen-binding protein), SPARC-like protein (a calcium binding cell signalling glycoprotein), and autotaxin t (a phosphodiesterase). It remains unknown whether these four proteins are related to the cause and pathogenesis of MS. PMID:15222687

Hammack, B N; Fung, K Y C; Hunsucker, S W; Duncan, M W; Burgoon, M P; Owens, G P; Gilden, D H



Glycoproteomics of cerebrospinal fluid in neurodegenerative disease  

NASA Astrophysics Data System (ADS)

Cerebrospinal fluid (CSF) from individual patients with Alzheimer's disease (AD) was separated by narrow range two-dimensional (2D) gel electrophoresis and analyzed by electrospray FT-ICR MS in this glycoproteomic study. Because several altered proteins in the comparison between AD patients and healthy controls individuals are isoforms of glycoproteins, it is important to determine if the modifying glycans are also altered. FT-ICR MS and fragmentation of glycopeptides with infrared multiphoton dissociation (IRMPD) offers abundant fragment ions through breakage at the glycosidic linkages with excellent mass accuracy, which facilitates the structural determination of the site-specific N-linked glycosylation. We present results from a structural comparison of proteins from three AD patients and three control individuals of different glycosylated isomers of [alpha]-1-antitrypsin, [beta]-trace and apolipoprotein J.

Sihlbom, Carina; Davidsson, Pia; Emmett, Mark R.; Marshall, Alan G.; Nilsson, Carol L.



Cerebrospinal fluid leak secondary to chiropractic manipulation  

PubMed Central

Background: There is a paucity of quality data on the incidence of adverse outcomes of chiropractic manipulation. Spontaneous intracranial hypotension (SIH) subsequent to cervical spinal manipulation has been documented. However, no imaging correlates have previously been presented demonstrating a clear causal relationship to manipulation with follow-up and correlating with clinical symptomatology. Case Description: We present a case of subacute cervical cerebrospinal fluid (CSF) leak resulting from chiropractic manipulation of the cervical spine. The patient is a 29-year-old female who received manipulation one week prior to developing symptoms of severe orthostatic headache, nausea, and vomiting. Magnetic resonance imaging (MRI) revealed a new C5-C6 ventral CSF collection. Symptomatic onset corresponded with the recent cervical chiropractic adjustment. We present serial imaging correlating with her symptomatology and review the pertinent literature on complications of chiropractic manipulation. Conclusion: Our case of ventral CSF leak with symptoms of intracranial hypotension demonstrated spontaneous symptomatic resolution without permanent neurological sequelae.

Kusnezov, Nicholas A.; Velani, Shamsha A.; Lu, Daniel C.



Cerebrospinal fluid leakage--reliable diagnostic methods.  


Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorrhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition. PMID:21334321

Mantur, Maria; ?ukaszewicz-Zaj?c, Marta; Mroczko, Barbara; Ku?akowska, Alina; Ganslandt, Oliver; Kemona, Halina; Szmitkowski, Maciej; Drozdowski, Wies?aw; Zimmermann, Rüdiger; Kornhuber, Johannes; Lewczuk, Piotr



Proteome analysis of chick embryonic cerebrospinal fluid.  


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

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



Cerebrospinal fluid pulse pressure waveform analysis in hydrocephalic children  

Microsoft Academic Search

Analysis of cerebrospinal fluid pulse pressure was reported to be useful in the assessment of the cerebrospinal pressure-volume compensation. The method for the estimation of high-frequency centroid (HFC) was modified and used to verify the correlation between HFC and other compensatory parameters investigated by means of the lumbar infusion test in 94 hydrocephalic children. The results confirm that in hydrocephalus

W. Zabolotny; M. Czosnyka; A. Walencik



Radioimmunological Evidence for Beta-Endorphin in Human Cerebrospinal Fluid.  

National Technical Information Service (NTIS)

Beta-endorphin-like immunoreactivity in human cerebrospinal fluid was determined by two different radioimmunoassays. Measurements made using a bought RIA-kit (Immuno Nuclear Corporation) produced results which were too high compared to results from the li...

M. Graf



Clinical pharmacokinetics of antibacterials in cerebrospinal fluid.  


In the past 20 years, an increased discrepancy between new available antibacterials and the emergence of multidrug-resistant strains has been observed. This condition concerns physicians involved in the treatment of central nervous system (CNS) infections, for which clinical and microbiological success depends on the rapid achievement of bactericidal concentrations. In order to accomplish this aim, the choice of drugs is based on their disposition toward the cerebrospinal fluid (CSF), which is influenced by the physicochemical characteristics of antibacterials. A reduced distribution into CSF has been documented for beta-lactams, especially cephalosporins and carbapenems, on the basis of their hydrophilic nature. However, they represent a cornerstone of the majority of combined therapeutic schemes for their ability to achieve bactericidal concentrations, especially in the presence of inflamed meninges. The good tolerability of beta-lactams makes possible high daily dose intensities, which may be associated with increased probability of cure. Furthermore, the adoption of continuous infusion seems to be a fruitful option. Fluoroquinolones, namely moxifloxacin, and antituberculosis drugs, together with the agents such as linezolid, reach the highest CSF/plasma concentration ratio, which is greater than 0.8, and for most of these drugs it is near 1. For all drugs that are currently used for the treatment of CNS infections, the evaluation of pharmacokinetic/pharmacodynamic parameters, on the basis of dosing regimens and their time-dependent or concentration-dependent pattern of bacterial killing, remains an important aspect of clinical investigation and medical practice. PMID:23605634

Di Paolo, Antonello; Gori, Giovanni; Tascini, Carlo; Danesi, Romano; Del Tacca, Mario




Microsoft Academic Search

Glucose levels in 154 random specimens of lumbar cerebrospinal fluid, normal as regards cell and protein content, were estimated by the glucose-oxidase method and a mean value of 60.5 mg.\\/100 ml. (S.D. 7.3) was obtained.In 33 fasting patients subject to air encephalography the mean cerebrospinal fluid (C.S.F.) glucose level was 56.5 mg., and mean blood glucose level 65.5 mg. with

Vincent Marks



Cerebrospinal Fluid Space Alterations in Melancholic Depression  

PubMed Central

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. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders.

Via, Esther; Cardoner, Narcis; Pujol, Jesus; Martinez-Zalacain, Ignacio; Hernandez-Ribas, Rosa; Urretavizacaya, Mikel; Lopez-Sola, Marina; Deus, Joan; Menchon, Jose Manuel; Soriano-Mas, Carles



New techniques and technology to repair cerebrospinal fluid rhinorrhea.  


Cerebrospinal fluid rhinorrhea occurs as a result of abnormal communication between the subarachnoid space and the pneumatized portion of the skull base, the paranasal sinuses and the middle ear. Conservative measures may be sufficient in the management of cerebrospinal fluid rhinorrhea, but, in some cases, surgical treatment may be required. Transnasal endoscopic techniques are constantly being used in preference to the intra- and extracranial approaches. Recently, image guidance systems have been adopted in neurosurgery, skull base and paranasal sinus surgery. The present report refers to 4 cases of nasal cerebrospinal fluid rhinorrhea leak successfully treated with a transnasal endoscopic approach using various techniques and materials to close the bone defect, in 2 of which, the navigation system (Stealth Station Treon ENT Image Guidance System with Landmark X, Software, Medtronic, XOMED, Jacksonville, FL, USA) was also used. In all cases, correct localization and repair of the leak was achieved and no major complications occurred. Following a review of the literature, the Authors conclude that, at present, transnasal endoscopic repair of cerebrospinal fluid rhinorrhea is the surgical treatment of choice when the techniques and materials are correctly used. Furthermore, preliminary findings indicate that it is possible to make routine use of the navigation systems and that this technology may be usefully employed, above all, in the management of cerebrospinal fluid leaks. PMID:15584583

Paludetti, G; Sergi, B; Rigante, M; Campioni, P; Galli, J



Cerebrospinal fluid lactic acid in diagnosis of meningitis.  

PubMed Central

Quantitative lactate determinations were performed on cerebrospinal fluids to assess their value in the rapid diagnosis of bacterial and mycotic meningitis and to evaluate their value in assessing the prognosis in these patients. Cerebrospinal fluid lactate concentrations were elevated in all patients with untreated bacterial or fungal meningitis. Lactate concentrations proved very valuable in following patients with mycotic meningitis and in differentiating aseptic from bacterial meningitis. Elevated cerebrospinal fluid lactate is not specific for meningitis. Lactate is also elevated in situations where there is central nervous system ischemia and necrosis and in patients with brain tumors. Lactate concentration is normal in chronic degenerative brain diseases. Thus, the clinical situation must be taken into account when interpreting the lactate concentrations.

Komorowski, R A; Farmer, S G; Hanson, G A; Hause, L L



Application of transport phenomena analysis technique to cerebrospinal fluid.  


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. PMID:24091435

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



Alterations in cerebrospinal fluid dopamine metabolites following physostigmine infusion  

Microsoft Academic Search

The effect of IV physostigmine administration on the cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in normal subjects was determined. After an adjustment for differing CSF concentrations of probenecid, physostigmine was found to elevate CSF HVA and DOPAC concentrations. The authors discuss these changes in CSF HVA and DOPAC and their possible relationship to the

Kenneth L. Davis; Kym F. Faull; Leo E. Hollister; Jack D. Barchas; Philip A. Berger



The function and structure of the cerebrospinal fluid outflow system  

Microsoft Academic Search

This review traces the development of our understanding of the anatomy and physiological properties of the two systems responsible for the drainage of cerebrospinal fluid (CSF) into the systemic circulation. The roles of the cranial and spinal arachnoid villi (AV) and the lymphatic outflow systems are evaluated as to the dominance of one over the other in various species and

Michael Pollay



Quantification of Free Fatty Acids in Human Cerebrospinal Fluid  

Microsoft Academic Search

Free fatty acids (FFA) in cerebrospinal fluid (CSF) are well-recognized markers of brain damage in animal studies. Information is limited regarding human CSF in both normal and pathological conditions. Samples of CSF from 73 patients, who had undergone lumbar puncture for medically indicated reasons, came from a core laboratory upon completion of ordered tests. Using high performance liquid chromatography, mean

J. G. Pilitsis; F. G. Diaz; J. M. Wellwood; M. H. O'Regan; M. R. Fairfax; J. W. Phillis; W. M. Coplin



More Than the Brain's Drain: Does Cerebrospinal Fluid Help the Brain Convey Messages?  

ERIC Educational Resources Information Center

|Examines the role of cerebrospinal fluid (CSF), a clear, colorless liquid that constantly bathes the brain and spinal cord. Scientists argue that cerebrospinal fluid carries important signals for sleep, appetite, and sex. Evaluates past and current research documenting the purpose of cerebrospinal fluid in the brain. (CCM)|

Travis, John



Cysticercus Antigens in Cerebrospinal Fluid Samples from Patients with Neurocysticercosis  

Microsoft Academic Search

Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried




Measurement of Cerebrospinal Fluid Output through External Ventricular Drainage in One Hundred Infants and Children: Correlation with Cerebrospinal Fluid Production  

Microsoft Academic Search

Objective: Cerebrospinal fluid (CSF) production rates influence shunt design and the care of children with hydrocephalus. Measurement of hourly CSF output through external ventricular drainage (EVD) reflects the CSF production. In the present study, hourly CSF outputs in children with hydrocephalus were measured while they were treated with EVD and correlated with the age, sex and body weight of the

Takasumi Yasuda; Tadanori Tomita; David G. McLone; Mark Donovan



Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria  

PubMed Central

Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-? (TNF-?), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-? levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-? production is associated with subsequent neurologic and cognitive morbidity.

John, Chandy C.; Panoskaltsis-Mortari, Angela; Opoka, Robert O.; Park, Gregory S.; Orchard, Paul J.; Jurek, Anne M.; Idro, Richard; Byarugaba, Justus; Boivin, Michael J.



Cerebrospinal fluid obstruction and malabsorption in human neonatal hydrocephaly  

Microsoft Academic Search

Introduction  The pathophysiology involved in human neonatal high-pressure hydrocephalus (HC) includes both cerebrospinal fluid (CSF) malabsorption and obstruction.Objective  The aim was to estimate the relative contribution between CSF malabsorption and obstruction in three different etiological groups of neonatal high-pressure HC by assessment of specific CSF biomarkers indicative of growth factor- and fibrosis-related CSF malabsorption (transforming growth factor beta-1 (TGF beta-1), aminoterminal propeptide

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



The electrical conductivity of human cerebrospinal fluid at body temperature  

Microsoft Academic Search

The electrical conductivity of human cerebrospinal fluid (CSF) from seven patients was measured at both room temperature (25 C) and body temperature (37 C). Across the frequency range of 10Hz-10 kHz, room temperature conductivity was 1.45 S\\/m, but body temperature conductivity was 1.79 S\\/m, approximately 23% higher. Modelers of electrical sources in the human brain have underestimated human CSF conductivity

Stephen B. Baumann; David R. Wozny; Shawn K. Kelly; Frank M. Meno



Dynamics of brain-derived proteins in cerebrospinal fluid  

Microsoft Academic Search

Background: The recent theory of blood–cerebrospinal fluid (CSF) barrier function and dysfunction connects molecular flux and CSF flow rate. A reduced CSF flow rate is sufficient to account for the observed hyperbolic relation between different blood-derived protein concentrations in CSF in cases of a blood–CSF barrier dysfunction. Methods: The dynamics of brain-derived proteins in CSF are investigated with reference to

Hansotto Reiber



Effect of Cerebral Injury on Cerebrospinal Fluid Cyclic AMP Concentration  

Microsoft Academic Search

Cerebrospinal fluid (CSF) cyclic adenosine-3’,5’-monophosphate (cAMP) was measured in rabbits after experimental brain injury as well as in patients with cerebral contusion and cerebral concussion. In rabbits a marked elevation lasting for two weeks was observed. From the third week onwards after the injury the CSF cAMP concentration was lower than the basal level before the injury. Dexamethasone partly inhibited

V. V. Myllylä



Gelsolin in Cerebrospinal Fluid as a Potential Biomarker of Epilepsy  

Microsoft Academic Search

Gelsolin is an actin regulatory protein that generally distributed in a wide variety of body tissues, especially the brain\\u000a tissues and cerebrospinal fluid. In this study we found that lumbar CSF-gelsolin concentrations markedly decreased in epileptic\\u000a patients by enzyme linked immunosorbent assay. In order to help judge the result, we determined gelsolin expression in temporal\\u000a lobe tissues of patients with

Xi Peng; Xiaogang Zhang; Liang Wang; Qiong Zhu; Jing Luo; Wei Wang; Xuefeng Wang


Amyloid and tau cerebrospinal fluid biomarkers in HIV infection  

Microsoft Academic Search

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 (sAPP? and sAPP?), amyloid beta fragment 1-42 (A?1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of

Magnus Gisslén; Jan Krut; Ulf Andreasson; Kaj Blennow; Paola Cinque; Bruce J Brew; Serena Spudich; Lars Hagberg; Lars Rosengren; Richard W Price; Henrik Zetterberg



Cerebrospinal fluid acetylcholinesterase and choline measurements in Huntington's disease  

Microsoft Academic Search

The caudate nucleus has the highest acetylcholinesterase (AChE) activity in the brain and it has been shown that autopsied brain tissue of patients with Huntington's disease (HD) have reduced levels of acetylcholine. Because of these findings, the cholinergic function in HD was studied by measuring cerebrospinal fluid (CSF) choline levels and AChE activity during a randomized, double-blind, cross-over, placebo-controlled clinical

B. V. Manyam; E. Giacobini; J. A. Colliver



Entry of diazepam and its major metabolite into cerebrospinal fluid  

Microsoft Academic Search

Five dogs received a single 1.0 mg\\/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3–1.3 h); DZ disappearance was mirrored by formation of DMDZ,

David J. Greenblatt; Hermann R. Ochs; Brian L. Lloyd



Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid  

Microsoft Academic Search

This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural\\u000a analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinal fluid (CSF) samples were obtained\\u000a from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased\\u000a levels of oleoylethanolamide in CSF (P = 0.011)

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



Evaluation and Management of Spontaneous Temporal Bone Cerebrospinal Fluid Leaks  

PubMed Central

Spontaneous temporal bone cerebrospinal fluid leak may be defined as a leak without an apparent precipitating cause. These transdural fistulas occur rarely, and diagnosis is predicated upon a high index of suspicion. Leaks have been reported through both middle and posterior fossa defects, although the vast majority involve the middle fossa plate. In a previous study we reported 7 cases of spontaneous temporal bone cerebrospinal fluid leaks, all involving the middle fossa tegmen. Upon further review of these cases and 5 previously unreported cases, the defect was localized to the tegmen tympani in 9 of the total 12 cases. Diagnostic methods are discussed, with the importance of high-resolution computed tomography stressed. The role of contrast cisternography is also evaluated. An outline for surgical management is presented based upon residual hearing and defect location and accessibility. A transmastoid procedure offers the advantage of visualization of both the middle and posterior fossa plates, and this approach can be supplemented with an obliterative procedure when indicated. The middle fossa approach provides optimal exposure of the tegmen plate with less likelihood of ossicular injury when dealing with tegmen tympani defects. Adjuncts to surgical therapy include intrathecal fluorescein dye and continuous postoperative lumbar cerebrospinal fluid drainage. ImagesFigure 1Figure 2Figure 3Figure 4

Pappas, Dennis G.; Hoffman, Ronald A.; Holliday, Roy A.; Hammerschlag, Paul E.; Pappas, Dennis G.; Swaid, Swaid N.



A chronic fatigue syndrome - related proteome in human cerebrospinal fluid  

PubMed Central

Background Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. Methods Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 ?l/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 ?l/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis. Results Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of ?1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were ?-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described. Conclusion This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared.

Baraniuk, James N; Casado, Begona; Maibach, Hilda; Clauw, Daniel J; Pannell, Lewis K; Hess S, Sonja



Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection.  


Sterile cerebrospinal fluid pleocytosis occurs in febrile infants with urinary tract infection. Coinfection with enterovirus is a possible cause. We evaluated 57 infants with urinary tract infection and cerebrospinal fluid pleocytosis. All had enterovirus testing by polymerase chain reaction. An explanation for pleocytosis was determined for 24 infants (42%). Enterovirus infection was detected in 4 and is an uncommon cause of cerebrospinal fluid pleocytosis in infants with urinary tract infection. PMID:23584580

Doby, Elizabeth H; Stockmann, Chris; Korgenski, E Kent; Blaschke, Anne J; Byington, Carrie L



Posttraumatic delayed cranio-orbital cerebrospinal fluid leakage: case report.  


A 56-year-old man sustained subarachnoid haemorrhage, skull base fracture and multiple facial fractures in a traffic accident. Two weeks later, the patient developed a subperiosteal fluid collection into the orbit of the right side presenting with a progressive proptosis and an increased intraocular pressure. We performed drainage of the fluid on the superior part of the right orbit, followed by a surgical reduction of the facial fractures. The patient had no exophthalmos any longer, whose intraocular pressure was normalised. In conclusion, our case indicates that careful monitoring of clinical signs and a follow-up radiography would be mandatory for patients with craniocerebral trauma despite a lack of the definite symptoms. Clinicians should consider the possibility that the cerebrospinal fluid (CSF) leakage into the orbit might occur in these patients. PMID:22959849

Rha, Eun Young; Kim, Ji Hwan; Byeon, Jun Hee



Chicken cerebrospinal fluid: normal composition and response to insulin administration  

PubMed Central

1. With the exception of Na, K and Cl clear cerebrospinal fluid (c.s.f.) obtained from chickens varying in age from 6 weeks to 2 years did not reveal significant alterations in composition as could be related to age per se. 2. Considerably higher levels of total protein and glucose are found in chicken c.s.f. than are found in mammalian fluid; slightly more chloride is found in chicken than most mammalian c.s.f.'s. 3. Intravenous beef insulin depressed chicken cerebrospinal fluid glucose levels; insulin placed intracisternally had no effect on the avian glycogen body glycogen content indicating that c.s.f. glucose constancy, with or without glycogen body assistance, is not responsible for the resistance of the chicken to pharmacological doses of insulin. 4. Bovine insulin injected into the cisterna magna of chickens depresses plasma glucose partially by acting over vagal pathways to release endogenous insulin and partially by diffusion across the c.s.f.—blood barrier to exert a peripheral effect.

Anderson, D. K.; Hazelwood, R. L.



Syndrome of spontaneous cerebrospinal fluid hypovolemia: report of six cases.  


Syndrome of spontaneous cerebrospinal fluid hypovolemia (SCH) is a rare cause of new onset headache. We report six cases of SCH presenting with new onset headache. All six cases were females. Acute onset orthostatic headache and neck pain were the chief characteristics of SCH in our cases. The MRI brain showed pachymeningeal gadolinium enhancement in all patients. Spinal extradural CSF collection was demonstrable on MRI in three cases. All cases improved with conservative therapy. High index of clinical suspicion and contrast enhanced MRI brain is the key to accurate diagnosis in the majority of cases. PMID:18040112

Ambady, Prakash; Ahsan Moosa, N V; Anand Kumar, A


Cerebrospinal fluid biomarkers in neurological diseases in children.  


Analysis of cerebrospinal fluid (CSF) biomarkers is an integral part of neurology. Basic CSF biomarkers, such as CSF/serum albumin ratio and CSF cell counts, have been used to diagnose inflammatory and infectious CNS disorders in adults and children for decades. During recent years, however, numerous biomarkers for neuronal and astroglial injury, as well as disease-specific protein inclusions, have been developed for neurodegenerative disorders in adults. The overall aim of this paper is to give an updated overview of some of these biomarkers with special focus on their possible relevance to neurological disorders in children and adolescents. PMID:23026858

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



Spontaneous cerebrospinal fluid rhinorrhea secondary to anterior fossa osteoradionecrosis.  


Osteoradionecrosis (ORN) after radiation therapy of head and neck or brain tumor most often presents in the mandible, followed by the maxillary bone. This case report describes a patient who presented with spontaneous cerebrospinal fluid (CSF) rhinorrhea 12 months after conventional external beam radiotherapy for frontotemporal anaplastic astrocytoma, and was diagnosed with anterior fossa ORN. Osteolysis in the anterior fossa on CT scan confirmed the diagnosis. A prompt temporal muscle graft with pericranial flap seal treated both the ORN and the CSF rhinorrhea, but observation would have been a suitable conservative option if ORN presented without CSF rhinorrhea. PMID:23517671

Hu, Zhebin; Godoy, Bruno L; Zadeh, Gelareh



Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.  

PubMed Central

In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time. This compound is the major metabolite of phenylethylamine, the production of which may be disturbed in a number of neuropsychiatric illnesses. Thus plasma measurements might be employed clinically to provide an estimate of central changes in phenylethylamine economy. A small but significantly higher proportion of conjugated phenylacetic acid was present in the plasma (but not cerebrospinal fluid) of Parkinsonians compared with controls.

Sandler, M; Ruthven, C R; Goodwin, B L; Lees, A; Stern, G M



CD4+ Cells Regulate Fibrosis and Lymphangiogenesis in Response to Lymphatic Fluid Stasis  

PubMed Central

Introduction Lymphedema is a chronic disorder that occurs commonly after lymph node removal for cancer treatment and is characterized by swelling, fibrosis, inflammation, and adipose deposition. Although previous histological studies have investigated inflammatory changes that occur in lymphedema, the precise cellular make up of the inflammatory infiltrate remains unknown. It is also unclear if this inflammatory response plays a causal role in the pathology of lymphedema. The purpose of this study was therefore to characterize the inflammatory response to lymphatic stasis and determine if these responses are necessary for the pathological changes that occur in lymphedema. Methods We used mouse-tail lymphedema and axillary lymph node dissection (ANLD) models in order to study tissue inflammatory changes. Single cell suspensions were created and analyzed using multi-color flow cytometry to identify individual cell types. We utilized antibody depletion techniques to analyze the causal role of CD4+, CD8+, and CD25+ cells in the regulation of inflammation, fibrosis, adipose deposition, and lymphangiogenesis. Results Lymphedema in the mouse-tail resulted in a mixed inflammatory cell response with significant increases in T-helper, T-regulatory, neutrophils, macrophages, and dendritic cell populations. Interestingly, we found that ALND resulted in significant increases in T-helper cells suggesting that these adaptive immune responses precede changes in macrophage and dendritic cell infiltration. In support of this we found that depletion of CD4+, but not CD8 or CD25+ cells, significantly decreased tail lymphedema, inflammation, fibrosis, and adipose deposition. In addition, depletion of CD4+ cells significantly increased lymphangiogenesis both in our tail model and also in an inflammatory lymphangiogenesis model. Conclusions Lymphedema and lymphatic stasis result in CD4+ cell inflammation and infiltration of mature T-helper cells. Loss of CD4+ but not CD8+ or CD25+ cell inflammation markedly decreases the pathological changes associated with lymphedema. In addition, CD4+ cells regulate lymphangiogenesis during wound repair and inflammatory lymphangiogenesis.

Elhadad, Sonia; Avraham, Tomer; Weitman, Evan; Mehrara, Babak J.



Cerebrospinal fluid biomarker candidates of schizophrenia: where do we stand?  


Here, we review the cerebrospinal fluid (CSF) candidate markers with regard to their clinical relevance as potential surrogates for disease activity, prognosis assessment, and predictors of treatment response. We searched different online databases such as MEDLINE and EMBASE for studies on schizophrenia and CSF. Initial studies on cerebrospinal fluid in patients with schizophrenia revealed increased brain-blood barrier permeability with elevated total protein content, increased CSF-to-serum ratio for albumin, and intrathecal production of immunoglobulins in subgroups of patients. Analyses of metabolites in CSF suggest alterations within glutamatergic neurotransmission as well as monoamine and cannabinoid metabolism. Decreased levels of brain-derived neurotrophic factor and nerve growth factor in CSF of first-episode patients with schizophrenia reported in recent studies point to a dysregulation of neuroprotective and neurodevelopmental processes. Still, these findings must be considered as non-specific. A more profound characterization of the particular psychopathological profiles, the investigation of patients in the prodromal phase or within the first episode of schizophrenia promoting longitudinal investigations, implementation of different approaches of proteomics, and rigorous adherence to standard procedures based on international CSF guidelines are necessary to improve the quality of CSF studies in schizophrenia, paving the way for identification of syndrome-specific biomarker candidates. PMID:22173848

Vasic, Nenad; Connemann, Bernhard J; Wolf, Robert C; Tumani, Hayrettin; Brettschneider, Johannes



A comprehensive proteome map of bovine cerebrospinal fluid.  


Cerebrospinal fluid (CSF) is considered as the most promising body fluid target for the discovery of biomarkers for early diagnosis of neurodegenerative diseases such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. For the recognition of disease-associated changes in bovine CSF protein patterns, a detailed knowledge of this proteome is a prerequisite. The absence of a high-resolution CSF proteome map prompted us to determine all bovine CSF protein spots that can be visualised on 2-D protein gels. Using state-of-the-art 2-DE technology for proteome mapping of bovine ante mortem CSF combined with sensitive fluorescent protein staining and MALDI-TOF/TOF MS for protein identification, a highly detailed 2-DE map of the bovine CSF proteome was established. Besides the proteins mapped by earlier studies, this map contains 66 different proteins, including 58 which were not annotated in bovine 2-DE CSF maps before. PMID:19921684

Brenn, Anja; Karger, Axel; Skiba, Martin; Ziegler, Ute; Groschup, Martin H



Optical analysis of suspended particles in the cerebrospinal fluid obtained by puncture from patients diagnosed with the disorders of cerebrospinal fluid (CSF) circulation  

NASA Astrophysics Data System (ADS)

The goal of the work was to determine the values of cumulative parameters of the cerebrospinal fluid. Values of the parameters characterise statistical cerebrospinal fluid obtained by puncture from the patients diagnosed due to suspicion of normotensive hydrocephalus. The cerebrospinal fluid taken by puncture for the routine examinations carried out at the patients suspected of normotensive hydrocephalus was analysed. In the paper there are presented results of examinations of several dozens of puncture samples of the cerebrospinal fluid coming from various patients. Each sample was examined under the microscope and photographed in 20 randomly chosen places. On the basis of analysis of the pictures showing the area of 100 x 100?m, the selected cumulative parameters such as count, numerical density, field area and field perimeter were determined for each sample. Then the average value of the parameters was determined as well.

Staro?, Waldemar; Herbowski, Leszek; Gurgul, Henryk



Development of a Nested PCR for Detection of Cryptococcus neoformans in Cerebrospinal Fluid  

Microsoft Academic Search

We report the development of a nested-PCR-based assay for the detection of Cryptococcus neoformans in cerebrospinal fluid. The specificity and sensitivity of the test were assessed. The technique was then applied to 40 cerebrospinal fluid samples. We obtained positive reactions for all 21 clinical samples from patients who had been previously diagnosed as having cryptococcal meningitis by conventional techniques and




Penetration of fusidic acid into human brain tissue and cerebrospinal fluid  

Microsoft Academic Search

Summary Penetration of fusidic acid into brain tissue in six patients and cerebrospinal fluid in seven patients was determined. Tissue samples, taken during surgery revealed drug levels at about 7% of simultaneous serum concentrations. In contrast, cerebrospinal fluid concentrations were below 1% of serum levels. Since serum- and tissue levels of fusidic acid were far above the minimal inhibitory concentration

Th Mindermann; W. Zimmerli; Z. Rajacic; O. Gratzl



Coronary artery bypass surgery in the presence of cerebrospinal fluid rhinorrhea.  


A seventy eight year old male patient was admitted in our hospital with headache, vomiting, irritability and confusion. Initially he was diagnosed as a case of pyogenic encephalitis. Further investigations revealed that patient had cerebrospinal fluid rhinorrhea and coronary artery disease. He successfully underwent coronary artery bypass grafting and cerebrospinal fluid leak repair. PMID:24107697

Rawat, Rajinder Singh; Mehta, Yatin; Trehan, Naresh; Gupta, Aditya


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

PubMed Central

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

Gonzalez-Marrero, Ibrahim; Castaneyra-Ruiz, Leandro; Gonzalez-Toledo, Juan M.; Castaneyra-Ruiz, Agustin; de Paz-Carmona, Hector; Castro, Rafael; Hernandez-Fernaud, Juan R.; Castaneyra-Perdomo, Agustin; Carmona-Calero, Emilia M.



The Choroid Plexuses and the Barriers Between the Blood and the Cerebrospinal Fluid  

Microsoft Academic Search

1. The fluid homeostasis of the brain depends both on the endothelial blood–brain barrier and on the epithelial blood–cerebrospinal fluid (CSF) barrier located at the choroid plexuses and the outer arachnoid membrane.

Malcolm B. Segal



Cerebrospinal fluid biopterin is decreased in Alzheimer's disease.  


Tetrahydrobiopterin is the cofactor in the hydroxylation of phenylalanine, tyrosine, and tryptophan leading to the eventual synthesis of the monoaminergic neurotransmitters, dopamine, norepinephrine, and serotonin, respectively. Total biopterin (90% of which is in the tetrahydro form) was measured in cerebrospinal fluid (CSF) and plasma of 30 patients with Alzheimer's disease and of 19 healthy controls. Plasma and CSF biopterin concentrations were not significantly correlated, but the mean CSF biopterin concentration in patients with Alzheimer's disease was significantly less than in age-matched controls, 13.5 pmol/mL as compared with 18.9 pmol/mL. The CSF biopterin concentration was not correlated with ventricular volume, as estimated by quantitative computed tomography, nor with the severity of dementia, as measured by various cognitive tests. The results suggest that a central biopterin deficiency exists in Alzheimer's disease. PMID:2428341

Kay, A D; Milstien, S; Kaufman, S; Creasey, H; Haxby, J V; Cutler, N R; Rapoport, S I



[A case report: a repeated cerebrospinal fluid otorrhea].  


Cerebrospinal fluid (CSF) otorrhea, leakage of CSF through the ear structures, may occur from a traumatic or operative defect in the skull, tumor, cholesteatoma, or congenital anomalies. A case of repeated CSF otorrhea is uncommon. In this report, we presented a case of a repeated CSF otorrhea which occurred a decade after the first middle ear surgery for chronic otitis media. The first CSF leakage, which might have been due to bone defects in the tegmen at the first middle ear sutgery, was surgically repaired using a transmastoid approach. However, CSF leakage with a meningoencephalocele occurred again 8 years after our first surgery for the CSF and the fistula was repaired using a transmiddle cranial fossa approach. Although 2 years have passed since the surgery, the CSF leakage has not recurred. PMID:23678672

Arai, Yasuhiro; Sakuma, Naoko; Sano, Daisuke; Takahashi, Masahiro; Matsuda, Hideki; Ikoma, Ryo; Sakane, Sayaka; Niwa, Kazutomo; Cho, Iemasa; Ishitoya, Junichi



Spontaneous Cerebrospinal Fluid Leaks Originating from Multiple Skull Base Defects  

PubMed Central

Spontaneous cerebrospinal fluid (CSF) leaks of temporal bone origin are more prevalent than once believed. Twenty-eight of the 61 cases documented in the world literature have been reported since 1992. All but four of these cases involved unilateral defects. The authors have previously reported experiences with 12 cases, with the vast majority of defects localized to the tegmen tympani. These patients also had demonstrated a single area of bone and dural dehiscence. We report two additional cases of spontaneous CSF leak originating from multiple/distant skull base defects. As in previously reported multisite cases, one of our patients demonstrated an elevated opening pressure on lumbar puncture. Significant time intervals existed between leak site presentations, which emphasizes the importance of careful follow-up for treated patients. Potential etiologies and associated factors are also discussed. This patient subset contributes another dimension to the evolving natural history of spontaneous CSF leakage. ImagesFigure 1Figure 2Figure 3

Pappas, Dennis G.; Pappas, Dennis G.; Hoffman, Ronald A.; Harris, Steven D.



Cerebrospinal Fluid Otorrhea Treated by Extended Subtotal Petrosectomy with Obliteration  

PubMed Central

Extended subtotal petrosectomy as a treatment for stubborn cerebrospinal fluid (CSF) otorrhea is presented. Nine patients were successfully operated on by this technique, all previously having undergone surgery for brain or base of skull lesions, other interventions used had failed to seal the fistula. The retrosigmoid cells, facial cells, and internal auditory canal were found in our study to be the most commonly involved during pervious neurosurgery and so constituted the usual path for CSF leakage. Total exenteration of middle ear and mastoid cell tracts, skeletization of sigmoid sinus, jugular bulb and facial nerve, drilling out of the semicircular canals, vestibulum, and cochlea, and skeletization of the internal auditory canal are the main steps of this approach.

Kronenberg, J.; Findler, G.; Braham, J.



Seizures with decreased levels of pyridoxal phosphate in cerebrospinal fluid.  


Although pyridoxine-dependent seizures have been reported for decades, pyridoxamine phosphate oxidase deficiency has only been recently described. Pyridoxamine phosphate oxidase (PNPO) is one of a series of enzymes involved in converting pyridoxine to pyridoxal 5'-phosphate, the biologically active form of pyridoxine. PNPO deficiency is associated with decreased levels of pyridoxal 5'-phosphate in CSF, as well as epilepsy. We describe four children up to 16 years of age with intractable seizures who all had low cerebrospinal fluid (CSF) levels of pyridoxal 5'-phosphate. Only one of the four children possessed a genetic alteration, a novel homozygous variant in exon one of the PNPO gene. Three of four, however, showed at least some clinical improvement with pyridoxal 5'-phosphate supplementation. Low CSF pyridoxal 5'-phosphate levels, although considered a diagnostic biomarker for PNPO deficiency, lack specificity and may result from multiple other causes. Genetic testing and CSF evaluation, along with clinical response are all necessary for accurate diagnosis. PMID:23419474

Goyal, Monisha; Fequiere, Pierre R; McGrath, Tony M; Hyland, Keith



Cerebrospinal fluid proteome of patients with acute Lyme disease  

PubMed Central

During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS) leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early-disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma.

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



Oligoclonal immunoglobulin G in cerebrospinal fluid of myasthenia gravis patients.  


Immunoglobulin G (IgG) band patterns were investigated in cerebrospinal fluid (CSF) from 19 patients with myasthenia gravis (MG) in a search for abnormalities indicating central nervous system (CNS) involvement in this disorder. Using the isoelectric focusing (IEF) technique and antiserum immunoblotting against IgG, we found no evidence of the presence of oligoclonal IgG in CSF from most of MG patients. In 2 cases, the positive findings of oligoclonal IgG in CSF may have reflected a manifestation of an associated disease, which has already been associated with immune abnormalities within the CNS. Further investigations with more sophisticated techniques are required to give additional insight into humoral immune events within the CNS in MG patients. PMID:2112820

Mavra, M; Apostolski, S; Nikolic, J; Thompson, E J



Meningothelial cells participate in immunological processes in the cerebrospinal fluid.  


Meningothelial cells (MECs) form the innermost layer of the meningeal sheath and as such are in direct contact with the cerebrospinal fluid (CSF) likely influencing CSF composition. The CSF space is a site of active immunological processes. To investigate an immunological role of MECs, cytokine and chemokine secretion, phagocytotic and pinocytotic activity by MECs was analyzed following stimulation with lipopolysaccharide, phorbol ester or rotenone. Secretion of IL-6 and IL-8 by MECs increased in a dose dependent manner after stimulation concomitant with NF-?B activation. In addition, phagocytotic clearance by MECs was enhanced suggesting an immunological role for MECs in the CSF compartment and pointing to a possible connection to neurodegenerative processes. PMID:22261544

Fan, Bin; Bordigari, Giovanna; Flammer, Josef; Killer, Hanspeter E; Meyer, Peter; Neutzner, Albert



Neonatal meningitis: mortality, cerebrospinal fluid, and microbiological findings.  


This study describes the bacteriology, cerebrospinal fluid (CSF) findings, and mortality of neonatal meningitis over an 11-year period. The minimum incidence of neonatal meningitis at Tygerberg Hospital is 0.72/1000 live births/year. Eighty-eight patients were included in the study. Median birthweight and age at diagnosis were 2320 g and 12 days, respectively. CSF culture was positive in 77 (88 per cent), blood culture was positive in 51 (57 per cent), and Gram stain was positive in 58 (66 per cent). The most frequently cultured organisms were Group B Streptococcus, Klebsiella pneumoniae, and E. coli. Thirty (34 per cent) patients died, the majority within 72 h after admission. The death rate was significantly increased in babies with a birthweight of less than 1500 g (59 per cent). Increased total CSF protein was associated with an increased risk of death. Normal CSF cell count, total CSF protein and CSF glucose were found in six infants. PMID:10996987

Nel, E



Confounding Factors Influencing Amyloid Beta Concentration in Cerebrospinal Fluid  

PubMed Central

Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of ?-amyloid (A?42). However, a high discrepancy between different centers in measured A?42 levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured A?42 level. Methods. Aliquots of CSF samples were either treated differently prior to A?42 measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF A?42 levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.

Bjerke, Maria; Portelius, Erik; Minthon, Lennart; Wallin, Anders; Anckarsater, Henrik; Anckarsater, Rolf; Andreasen, Niels; Zetterberg, Henrik; Andreasson, Ulf; Blennow, Kaj



Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.  


Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted. PMID:20798852

Bjerke, Maria; Portelius, Erik; Minthon, Lennart; Wallin, Anders; Anckarsäter, Henrik; Anckarsäter, Rolf; Andreasen, Niels; Zetterberg, Henrik; Andreasson, Ulf; Blennow, Kaj



Increased cerebrospinal fluid cAMP levels in Alzheimer's disease.  


Since increasing evidence suggests that upregulation of the cAMP-second messenger system may be implicated in Alzheimer's disease neurodegeneration, we have compared the cAMP and cGMP levels in cerebrospinal fluid (CSF) from patients with dementia of the Alzheimer type (DAT, n=10) with those from nondemented age-matched controls (n=10). Our results show that cAMP levels, but not cGMP, are significantly (p<0.01) elevated in CSF from patients with DAT compared to those from nondemented controls. Moreover, a linear regression analysis demonstrated a significant correlation (r=0.62; p<0.01) between cAMP and tau protein levels in CSF when controls and patients with DAT were studied together. These results suggest that upregulation of cAMP-signaling pathway is implicated in Alzheimer's disease physiopathology. PMID:10556645

Martínez, M; Fernández, E; Frank, A; Guaza, C; de la Fuente, M; Hernanz, A



Endoscopic repair of cerebrospinal fluid rhinorrhoea in a developing country.  


The objectives of the study was to determine the causes and outcome of endoscopic repair of cerebrospinal fluid (CSF) leak in a developing country. A total of five patients were recruited in the study. The age of patients ranged from 8 to 65 years. Four patients were male and one was female. In two cases of iatrogenic injury, the first was in the sphenoid sinus. The second was following functional endoscopic sinus surgery (FESS). Fascia lata was used to repair all cases. Beriplast was used as sealing agent in four cases and clotted blood was used in remaining case. Despite the small number, CSF rhinor rhoea was resolved in all cases. The patients were followed up for 2.5 to 6.5 years. Endoscopic repair is a viable option even in developing countries. It is cost effective and has a very low morbidity rate with no mortality at all. PMID:23139989

Akhter, Saeed; Zia, Sadaf; Zafar, Rafay



Cerebrospinal Fluid Proteomics Reveals Potential Pathogenic Changes in the Brains of SIV-infected Monkeys  

PubMed Central

The HIV-1-associated neurocognitive disorder occurs in approximately one-third of infected individuals. It has persisted in the current era of anti-retroviral therapy, and its study is complicated by the lack of biomarkers for this condition. Since the cerebrospinal fluid is the most proximal biofluid to the site of pathology, we studied the cerebrospinal fluid in a nonhuman primate model for HIV-1-associated neurocognitive disorder. Here we present a simple and efficient liquid chromatography coupled mass spectrometry based proteomics approach that utilizes small amounts of cerebrospinal fluid. First, we demonstrate the validity of the methodology using human cerebrospinal fluid. Next, using the simian immunodeficiency virus infected monkey model, we show its efficacy in identifying proteins such as alpha-1-antitrypsin, complement C3, hemopexin, IgM heavy chain and plasminogen, whose increased expression is linked to disease. Finally, we find that the increase in cerebrospinal fluid proteins is linked to increased expression of their genes in the brain parenchyma, revealing that the cerebrospinal fluid alterations identified reflect changes in the brain itself and not merely leakage of the blood-brain or blood- cerebrospinal fluid barriers. This study reveals new central nervous system alterations in lentivirus-induced neurological disease, and this technique can be applied to other systems in which limited amounts of biofluids can be obtained.

Pendyala, Gurudutt; Trauger, Sunia A.; Kalisiak, Ewa; Ellis, Ronald J.; Siuzdak, Gary; Fox, Howard S.



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


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

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



Cysticercus Antigens in Cerebrospinal Fluid Samples from Patients with Neurocysticercosis  

PubMed Central

Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n = 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried out with the anti-Tso, anti-Tcra, and anti-Tcra <30 kDa showed sensitivities of 81.2, 90, and 95.8% and specificities of 82, 98, and 100%, respectively. The 14- and 18-kDa low-molecular-weight peptides were only detected in CSF samples from patients with NC by immunoblotting with anti-Tso and anti-Tcra sera. Because of the importance of the diagnosis and prognosis of cysticercosis, the detection of antigens may contribute as an additional marker to the study and clarification of the parasite-host relationship.

Pardini, Alessandra Xavier; Vaz, Adelaide Jose; Machado, Luis Dos Ramos; Livramento, Jose Antonio



Differentiation of communicating hydrocephalus and presenile dementia by continuous recording of cerebrospinal fluid pressure.  

PubMed Central

Continuous monitoring of the cerebrospinal fluid pressure and observation of the pressure during intrathecal infusion of normal saline at two rates were performed in patients with communicating hydrocephalus and cerebral atrophy of other causes. Constant or temporarily increased cerebrospinal fluid pressure was observed only in communicating hydrocephalus. Reduction of intracranial pressure by a ventriculoatrial shunt was associated with clinical improvement. The intrathecal infusion test was capable of detecting reduced absorption of cerebrospinal fluid if more than one infusion rate was employed. Using both tests it is easier to determine which patients with communicating hydrocephalus should be treated with a shunt operation. Images

Hartmann, A; Alberti, E



Review of "Proteins of the Cerebrospinal Fluid" (2nd Edition) by Edward J. Thompson  

PubMed Central

This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF.

Connor, James R



Human herpesvirus 8 DNA in the cerebrospinal fluid of a patient with sensory impairment.  


This note reports the finding of human herpes virus 8 DNA in the cerebrospinal fluid of a woman with sensory impairment correlated with a basal disease suspected to be multiple sclerosis. PMID:11718379

Portolani, M; Sabbatini, A M; Gennari, W; Beretti, F; Greco, G; Santangelo, M



The Effect of Dexamethasone on the Formation Rate of Cerebrospinal Fluid in Monkeys.  

National Technical Information Service (NTIS)

A standard ventriculocisternal perfusion technique was used to determine what effect a single large intravenous dose of dexamethasone would have on cerebrospinal fluid (CSF) formation rate in the rhesus monkey over a 4-hour period. Three monkeys received ...

A. N. Martins A. Ramirez L. S. Solomon G. M. Wiese



Autoradiographische Untersuchungen an Liquorzellen. (Autoradiographic investigations of cells from the cerebrospinal fluid).  

National Technical Information Service (NTIS)

A total of 155 samples of cerebrospinal fluid obtained from 61 patients were subjected to cytological examination and incubated together with /sub 3//sup 1/H-thymidine. Radioactive labelling was thus achieved for lymphocytes, monocytes and tumour cells. T...

W. Thamm



Cellulose Acetate Electrophoresis of Cerebrospinal Fluid Proteins with Normal Values of 135 Persons.  

National Technical Information Service (NTIS)

A study on cellulose acetate electrophoresis of cerebrospinal fluid (CSF) proteins is reported. Two methods are used for concentration, acetone precipitation and sephadex dialysis with slight modifications. They are both considered to be clinically valuab...



Investigation of Cerebrospinal Fluid Shunt Valves: Test Results for Twenty-Five Valves.  

National Technical Information Service (NTIS)

The report describes the result of an investigation of design and implement a bench test for cerebrospinal fluid shunt valves. The original contract was extended for the purpose of utilizing the bench test to analyze 25 additional commercially available h...

H. D. Keith R. L. Lu C. C. Fu S. Shao



Concentrations of Cefpirome in Cerebrospinal Fluid of Children with Bacterial Meningitis after a Single Intravenous Dose  

PubMed Central

A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (n = 5) was 10.8 (7.8) ?g/ml. Drug concentrations in cerebrospinal fluid above the MIC for Streptococcus pneumoniae at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant S. pneumoniae.

Friedland, Ian R.; Sultan, Eric; Lehr, Karl H.; Lenfant, Bernard



Study on spontaneous cerebrospinal fluid rhinorrhoea: its aetiology and management.  


The aim of this study was to identify the common features in a study group of patients with spontaneous cerebrospinal fluid (CSF) rhinorrhoea, to develop a hypothesis to explain the cause of this condition and to investigate the outcome of surgical techniques adopted to repair the leak. In this retrospective study the authors have reviewed all the cases of spontaneous CSF leaks attending and receiving treatment from the otolaryngology department of Queen Elizabeth Hospital, Birmingham, from 1992 to 2002. Of 34 patients with CSF leaks, 15 were spontaneous in nature and formed the study group. Of these 15 patients, 14 were female; with ages ranging from 37 to 70 years and a median age of 50 years. All the female patients were overweight with a body mass index (BMI) >24.9 and, of these, nine were considered obese with a BMI >30. It was attempted to identify common factors in the study group and it was evident that female sex, obesity and age played a key role in this condition. The follow-up period ranged from two to 98 months. Thirteen patients were asymptomatic but two patients remained symptomatic, one of these despite repeated surgical intervention. PMID:15807955

Dunn, C J; Alaani, A; Johnson, A P



Proteomics Analysis of Perilymph and Cerebrospinal Fluid in Mouse  

PubMed Central

Objectives Proteins in perilymph may alter the delivery profile of implantable intracochlear drug delivery systems through biofouling. Knowledge of protein composition will help anticipate interactions with delivered agents. Study Design Analysis of mouse perilymph. Methods Protein composition of perilymph and cerebrospinal fluid (CSF) was analyzed using a capillary liquid chromatography-mass spectrometry-based iTRAQ quantitative proteomics approach. We searched against a mouse subset of the Uniprot FASTA protein database. We sampled perilymph from the apex of the mouse cochlea to minimize CSF contamination. Results More than 50 explicit protein isoforms were identified with very high confidence. iTRAQ reporter ions allowed determination of relative molar amounts of proteins between perilymph and CSF. Protein in perilymph was almost three times more concentrated than in CSF. More than one-third of the proteins in perilymph comprised protease inhibitors, with serpins being the predominant group. Apolipoproteins constituted 16%. Fifteen percent of the proteins were enzymes. Albumin was the most abundant single protein (14%). Proteins with relatively high perilymph/CSF ratios included broad-spectrum protease inhibitors and apolipoproteins. Discussion Some proteins found in perilymph, such as albumin and HMW kininogen, have been implicated in biofouling through adsorption to device materials. The relatively large quantities of apolipoprotein and albumin may serve as a reservoir for acidic and lipophillic drugs. Alpha-2-glycoprotein can bind basic drugs. Conclusions Perilymph is similar in protein composition to CSF, though amounts are 2.8 times higher. Protease inhibitors comprise the largest category of proteins.

Leary Swan, Erin E.; Peppi, Marcello; Chen, Zhiqiang; Green, Karin M.; Evans, James E.; McKenna, Michael J.; Mescher, Mark J.; Kujawa, Sharon G.; Sewell, William F.



Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus  

PubMed Central

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, A?42, NFL, TNF-?, TGF?1, 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-? concentration was low in iNPH patients.

Leinonen, Ville; Menon, Lata G.; Carroll, Rona S.; Dello Iacono, Donna; Grevet, Jeremy; Jaaskelainen, Juha E.; Black, Peter M.



Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus.  


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, ptau(181), A?(42), NFL, TNF-?, TGF?1, 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-? concentration was low in iNPH patients. PMID:21660204

Leinonen, Ville; Menon, Lata G; Carroll, Rona S; Dello Iacono, Donna; Grevet, Jeremy; Jääskeläinen, Juha E; Black, Peter M



Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer's disease  

PubMed Central

The frequent co-occurrence of Alzheimer disease (AD) pathology in patients with normal pressure hydrocephalus suggests a possible link between ventricular dilation and AD. If enlarging ventricles serve as a marker of faulty cerebrospinal fluid (CSF) clearance mechanisms, then a relationship may be demonstrable between increasing ventricular volume and decreasing levels of amyloid beta peptide (A?) in CSF in preclinical and early AD. CSF biomarker data (A?, tau, and phosphorylated tau) as well as direct measurements of whole brain and ventricular volumes were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset. The ratio of ventricular volume to whole brain volume was derived as a secondary independent measure. Baseline data were used for the group analyses of 288 subjects classified as being either normal (n=87), having the syndrome of mild cognitive impairment (n=136), or mild AD (n=65). Linear regression models were derived for each biomarker as the dependent variable, using the MRI volume measures and age as independent variables. For controls, ventricular volume was negatively associated with CSF A? in APOE ?4 positive subjects. A different pattern was seen in AD subjects, in whom ventricular volume was negatively associated with tau, but not A? in ?4 positive subjects. Increased ventricular volume may be associated with decreased levels of CSF A? in preclinical AD. The basis for the apparent effect of APOE ?4 genotype on the relationship of ventricular volume to A? and tau levels is unknown, but could involve altered CSF-blood-brain barrier function during the course of disease.

Ott, Brian R.; Cohen, Ronald A.; Gongvatana, Assawin; Okonkwo, Ozioma C.; Johanson, Conrad E.; Stopa, Edward G.; Donahue, John E.; Silverberg, Gerald D.



Cerebrospinal fluid rhinorrhea: An institutional perspective from Pakistan  

PubMed Central

Background: The management of cerebrospinal fluid (CSF) rhinorrhea has evolved over the last two decades. We present here a review of our 11-year data on CSF rhinorrhea and its management at a tertiary care hospital in a developing country, with particular reference to the diagnosis, surgical management and outcome of the disease. Methods: The medical charts of all patients with a diagnosis of CSF rhinorrhea over an 11-year period were reviewed. The etiology of CSF rhinorrhea was classified into three categories: spontaneous, iatrogenic and traumatic. All the patients were divided into three categories based on the type of management as conservative, intracranial and transnasal endoscopic groups. Results: A total of 43 patients fulfilled our inclusion criteria and were included in the final analysis. Eleven of the 43 patients were managed conservatively, while 22 underwent intracranial repairs; 10 patients had transnasal endoscopic repairs. The primary success rate for the transnasal approach was 70% compared to 86% for the intracranial repair. Blood loss, special care unit (SCU) stay and total cost were found to be significantly less in the transnasal endoscopic group. Computed tomography (CT) cisternography was found to have the highest sensitivity and specificity. Further, no postoperative complications were found in the transnasal endoscopic group, while five patients from the intracranial group developed various complications. Conclusions: We conclude that the transnasal endoscopic approach has comparable success rates with the intracranial approach and significantly lower morbidity.

Tahir, Muhammad Zubair; Khan, Muhammad Babar; Bashir, Muhammad Umair; Akhtar, Shabbir; Bari, Ehsan



Raltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection  

PubMed Central

Introduction 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. Methods 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. Results 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. Conclusions Approximately 50% of the CSF specimens exceeded the IC95 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.

Yilmaz, Aylin; Gisslen, Magnus; Spudich, Serena; Lee, Evelyn; Jayewardene, Anura; Aweeka, Francesca; Price, Richard W.



Cerebrospinal fluid apolipoprotein E levels in subacute sclerosing panencephalitis.  


Neurofibrillary tangles (NFTs) have been shown in 20% of subacute sclerosing panencephalitis (SSPE) cases. NFTs contain paired helical filaments formed by hyperphosphorylated tau. The intraneuronal tau metabolism and the rate of formation of paired helical filaments can be regulated by interactions between tau and isoforms of Apolipoprotein E (Apo E). Tau binds in vitro to Apo E3, interferes with the hyperphosphorylation of tau and may reduce the formation of NFTs. We investigated cerebrospinal fluid (CSF) Apo E levels in SSPE (n=37) and age-matched control (n=38) groups. The median level of total Apo E and Apo E4 were lower in the SSPE than the control group (p<0.001 and p=0.002). On the other hand, median Apo E3 level (0.28±0.23 ?g/ml) was higher in the SSPE group (p<0.001). Such elevated levels of ApoE3 might play a role in controlling the formation of NFTs in SSPE. Because NFT-associated neurodegeneration is a slow process, comparison of the long-term clinical course of SSPE cases with high and low Apo E3 levels might provide further understanding or the role of these molecules in this disease, and help the planning of neuroprotective treatment. PMID:21788110

Yüksel, Deniz; Ichiyama, Takashi; Yilmaz, Deniz; Anlar, Banu



Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid  

PubMed Central

Purpose Radioimmunotherapy (RIT) using 131I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of 131I-3F8 and to identify limiting factors that may impact therapeutic ratio. Methods Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[CIAR]), (2) that of the unbound antibody AUC[CIA], and (3) their therapeutic ratio (AUC [CIAR]/AUC[CIA]). Results Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R=0.95±0.03). Correlations were substantially better when compared to the one-compartment model (R=0.92±0.11 versus 0.77±0.21, p=0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of 131I-3F8 from 10% to 90% increased both (AUC[CIAR]) and therapeutic ratio ([AUC[CIAR]/AUC[CIA

He, Ping; Kramer, Kim; Smith-Jones, Peter; Zanzonico, Pat; Humm, John; Larson, Steven M.



Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies.  


The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10-15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD. PMID:19444528

Ladogana, Anna; Sanchez-Juan, Pascual; Mitrová, Eva; Green, Alison; Cuadrado-Corrales, Natividad; Sánchez-Valle, Raquel; Koscova, Silvia; Aguzzi, Adriano; Sklaviadis, Theodoros; Kulczycki, Jerzy; Gawinecka, Joanna; Saiz, Albert; Calero, Miguel; van Duijn, Cornelia M; Pocchiari, Maurizio; Knight, Richard; Zerr, Inga



Soluble CD146 in cerebrospinal fluid of active multiple sclerosis.  


The soluble form of CD146 has been reported to be present in various inflammatory diseases and displays pro-inflammatory properties. However, little is known about sCD146 in multiple sclerosis (MS). Here we show that sCD146 is significantly elevated in the cerebrospinal fluid of patients with active MS compared with that of inactive MS or patients with non-demyelinating diseases. Moreover, abnormally increased sCD146 in the CSF of active MS patients correlated with albumin quotient, MBP antibody and MOG antibody from both CSF and sera. Importantly, the level of CSF sCD146 is correlated with levels of inflammatory factors, such as TNF?, IFN?, IL-2, and IL-17A in the CSF. We also found that CSF sCD146 might originate from membrane-bound CD146 on inflamed blood-brain barrier (BBB) endothelial cells. In addition, sCD146 promotes leukocyte transmigration in vitro, at least in part by stimulating the expression of ICAM-1 and VCAM-1 on endothelial cells. Our findings suggest that CSF levels of sCD146 may provide a potential marker for monitoring disease activity in MS patients. PMID:23333866

Duan, H; Luo, Y; Hao, H; Feng, L; Zhang, Y; Lu, D; Xing, S; Feng, J; Yang, D; Song, L; Yan, X



Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects  

PubMed Central

1. Objectives Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinal fluid (CSF) of neuropathologically confirmed PD cases. 2. Methods We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference gel electrophoresis (2D-DIGE). Spots exhibiting a 1.5-fold or greater difference in volume between PD patients and controls were excised from the 2D gels, subjected to tryptic digestion and identification of peptides assigned using mass spectrometric/data bank correlation methods. 3. Results Employing this strategy six molecules: fibrinogen, transthyretin, apolipoprotein E, clusterin, apolipoprotein A-1 and glutathione-S-transferase-Pi were found to be different between PD and NC populations. 4: Discussion These molecules have been implicated in PD pathogenesis. Combining biomarker data from multiple laboratories may create a consensus panel of proteins that may serve as a diagnostic tool for this neurodegenerative disorder.

Maarouf, Chera L.; Beach, Thomas G.; Adler, Charles H.; Shill, Holly A.; Sabbagh, Marwan N.; Wu, Terence; Walker, Douglas G.; Kokjohn, Tyler A.; Roher, Alex E.



Cerebrospinal fluid biomarkers mirror rate of cognitive decline.  


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

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



Primary spontaneous cerebrospinal fluid leaks located at the clivus  

PubMed Central

Transclival meningoceles and primary spontaneous cerebrospinal fluid (CSF) leaks at the clivus are extremely rare lesions and only few of them have been reported in the literature. We report here six cases of transclival primary spontaneous CSF leaks through the clivus. A retrospective case study was performed. We reviewed six cases involving sinonasal CSF leaks located at the clivus treated between 1997 and 2009. Presenting symptoms, duration of symptoms, defect size, site of defect, surgical approach and technique of defect closure, intraoperative complications, postoperative complications, and recurrences are discussed. All CSF leaks were located in the upper central part of the clivus. two of six patients showed signs of increased intracranial pressure (ICP) including arachnoid pits and/or empty sella. For three patients a purely transnasal approach was used with multilayer reconstruction using a nonvascularized graft, and three patients underwent a transnasal transseptal approach with a multilayer reconstruction, with nasoseptal flap. No recurrences of CSF leaks at clivus or other sites were observed to date with a mean follow-up of 10.3 years (range, 3–15 years). Spontaneous CSF rhinorrhea located at the clivus is an extremely rare condition. To date, only eight cases have been described. Here, we report the largest group of six consecutive cases. Irrespective of the used reconstruction technique in all cases a 100% closure rate was achieved. However, identification of increased ICP is an essential aspect and this condition should be treated either medically or surgically.

Kitice, Adriano; Vellutini, Eduardo; Balsalobre, Leonardo; Stamm, Aldo



Antibodies to Schistosoma mansoni in human cerebrospinal fluid.  


Cerebrospinal fluid (CSF) and serum samples from patients suspected of having neuroschistosomiasis (NS) were evaluated by an enzyme-linked immunosorbent assay. Monoclonal antibodies of various immunoglobulin isotypes (IgM, IgA, IgE, total IgG, IgG1, IgG2, IgG3, and IgG4) were used to detect antibodies against Schistosoma mansoni soluble egg antigen (SEA) and soluble worm adult preparation (SWAP). Of the 83 CSF samples tested, 55% were reactive to SEA (26% were reactive only to SEA and 29% to both SEA and SWAP), 34% were reactive to SWAP (5% only to SWAP and 29% to both SEA and SWAP), and 40% were not reactive with any antigen. Cases that tested positive for SWAP in CSF and negative in serum were not found. Samples with high specific IgG antibody titers were selected for immunoglobulin isotype profiling. In the CSF samples, the antibodies against SEA and SWAP were mainly IgM, IgG1, and IgG4, although other immunoglobulins were also detected. Interestingly, nine patients had high levels of IgG1 only in the CSF. These results suggest that there is local synthesis of IgG1, and that this isotype could be an important immunologic marker in the diagnosis of NS. PMID:12685632

Magalhães-Santos, Isis F; Lemaire, Denise C; Andrade-Filho, Antonio S; Queiroz, Aristides C; Carvalho, Otávio M; Carmo, Theomira M A; Siqueira, Isadora C; Andrade, Débora M; Rego, Michely F; Guedes, Ana Paula T; Reis, Mitermayer G



Choroid plexus protects cerebrospinal fluid against toxic metals  

SciTech Connect

Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cysteine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.

Wei, Zheng; Perry, D.F.; Nelson, D.L.; Aposhian, H.V. (Univ. of Arizona, Tucson (United States))



Spontaneous skull base meningoencephaloceles and cerebrospinal fluid fistulas.  


Cerebrospinal fluid (CSF) fistulas are characterized by the egress of CSF from the intracranial cavity through an osteodural disruption between the subarachnoid space and a pneumatized structure within the skull base. Depending on the cause, CSF fistulas are classified as acquired or congenital, and acquired fistulas are further classified as traumatic, nontraumatic, or spontaneous. Spontaneous CSF fistulas are considered to result from a multifactorial process and have been postulated to represent a variant of idiopathic intracranial hypertension. However, an anatomic predisposition involving thinning of the cranial base, such as pneumatization of the sinus walls, must also be present. This process creates areas of structural weakness that act as potential pathways for CSF leaks, which most commonly occur in the ethmoid roof, sphenoid sinus, and temporal bone. Because CSF leaks may be overlooked, a result of their asymptomatic or subtle, intermittent course, a high level of suspicion is crucial in making an early diagnosis. However, CSF fistulas may be well seen at computed tomography (CT), which depicts bone defects, and magnetic resonance cisternography, which reveals the contents of herniated tissue. Knowledge of the location and size of the bone defect and herniated contents is crucial for the selection of surgical approach and grafting material. PMID:23479713

Alonso, Raquel Cano; de la Peña, Mar Jimenez; Caicoya, Anne Gomez; Rodriguez, Manuel Recio; Moreno, Elena Alvarez; de Vega Fernandez, Vicente Martinez


Surgical challenge: endoscopic repair of cerebrospinal fluid leak  

PubMed Central

Background Cerebrospinal fluid leaks (CSF) result from an abnormal communication between the subarachnoid space and the extracranial space. Approximately 90% of CSF leak at the anterior skull base manifests as rhinorrhea and can become life-threatening condition. Endoscopic sinus surgery (ESS) has become a common otolaryngologist procedure. The aim of this article is to consider our experience and to evaluate the outcomes in patients who underwent a purely endoscopic repair of CSF leaks of the anterior skull base. Findings Retrospective chart review was performed of all patients surgically treated for CSF leaks presenting to the Section of Nasal and Sinus Disorders at the Service of ENT–Head and Neck Surgery, University Hospital Complex of Santiago de Compostela (CHUS), between 2004 and 2010. A total of 30 patients who underwent repair CSF leak by ESS. The success rate was 93.4% at the first attempt; only two patients (6.6%) required a second surgical procedure, and none of it was necessary to use a craniotomy for closure. Follow-up periods ranged from 4?months to 6?years. Conclusion Identifying the size, site, and etiology of the CSF leak remains the most important factor in the surgical success. It is generally accepted that the ESS have made procedures minimally invasive, and CSF leak is now one of its well-established indications with low morbidity and high success rate, with one restriction for fistulas of the posterior wall of the frontal sinus should be repaired in conjunction with open techniques.



Reduction of Cerebrospinal Fluid Pressure by Hypocapnia: Changes in Cerebral Blood Volume, Cerebrospinal Fluid Volume, and Brain Tissue Water and Electrolytes  

Microsoft Academic Search

Summary: The study examined the role of cerebral blood volume (CBV), cerebrospinal fluid (CSF) volume, and brain tissue water and electrolytes on CSF pressure during 4 h of hypocapnia in dogs. Group I (n = 6) was examined during hypocapnia (Paco2 20 mm Hg), with no intracranial mass being present. Group II (n = 6) was examined with an intracranial

Alan A. Artru



Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and Progression  

PubMed Central

Background There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or ?-synuclein in the cerebrospinal fluid (CSF) is a potential index for PD diagnosis, but not for PD severity. Methods Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (A?1-42), Flt3 ligand and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these five markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and ?-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally. Findings The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/A?1-42 that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples. Interpretation We have demonstrated that this panel of seven CSF proteins could aid in PD diagnosis, differential diagnosis, and correlation with disease severity and progression.

Shi, Min; Bradner, Joshua; Hancock, Aneeka M.; Chung, Kathryn A.; Quinn, Joseph F.; Peskind, Elaine R.; Galasko, Douglas; Jankovic, Joseph; Zabetian, Cyrus P.; Kim, Hojoong M.; Leverenz, James B.; Montine, Thomas J.; Ginghina, Carmen; Kang, Un Jung; Cain, Kevin C.; Wang, Yu; Aasly, Jan; Goldstein, David S.; Zhang, Jing



Serum and cerebrospinal fluid cytokine concentrations in subacute sclerosing panencephalitis.  


Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease due to persistent measles virus infection. Its immunopathogenesis is unknown. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-6, IL-10 and IL-4 concentrations were measured in cerebrospinal fluid (CSF) and serum samples from 30 SSPE patients and 19 control subjects by cytometric bead array. CSF and serum IFN-gamma, IL-12 and IL-18 levels were measured in 18 SSPE patients by ELISA. Serum IL-4 and IL-10 (p<0.001), CSF IL-4 (p<0.001) and IL-6 (p=0.049) concentrations were lower, and serum IL-2 concentrations, higher (p=0.001) in SSPE patients. Serum TNF-alpha and IL-6, CSF TNF-alpha, IL-10, and IL-2 concentrations were not different between SSPE and control groups. Serum IFN-gamma levels were higher in stage I and II than stage III patients (p<0.05), whereas there was no difference between stages in terms of other cytokines. The levels of Th2-type cytokines: IL-4, IL-6 and IL-10 were suppressed in our SSPE cases. This finding, along with relatively elevated IFN-gamma and IL-2 levels, may suggest more active effector T cells compared to regulatory T cells (Treg), especially induced Treg, in early disease. High serum IL-2 concentrations might indicate peripheral Th1 activation. Discrepancies between various reports in the literature should be examined in view of the ages, stage and treatments of the patients studied. The interplay of various cytokines or cellular systems which may vary over time and between patients. Studies of treatment measures favoring the preservation of the early inflammatory response may be of interest in SSPE. PMID:19481385

Aydin, Omer Faruk; Ichiyama, Takashi; Anlar, Banu



Characterization of Acid Sphingomyelinase Activity in Human Cerebrospinal Fluid  

PubMed Central

Background As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. Methods An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF) collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. Results We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme’s properties. The enzyme resembles plasmatic ASM including protein stability and Zn2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. Conclusions Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.

Muhle, Christiane; Huttner, Hagen B.; Walter, Silke; Reichel, Martin; Canneva, Fabio; Lewczuk, Piotr; Gulbins, Erich; Kornhuber, Johannes



Cerebrospinal Fluid Biomarkers, Education, Brain Volume and Future Cognition  

PubMed Central

Objective To evaluate the combination of cerebrospinal fluid biomarkers of A?42, tau, and phosphorylated tau (ptau181) with education and normalized whole brain volume (nWBV) to predict incident cognitive impairment and test the cognitive/brain reserve hypothesis. Design Longitudinal cohort study. Setting Charles F. and Joanne Knight Alzheimer’s Disease Research Center of Washington University, St. Louis, Missouri. Participants Convenience sample of 197 participants aged 50 years and above, with normal cognition (Clinical Dementia Rating [CDR] of 0) at baseline, followed for a mean of 3.3 years. Main outcome measure Time to cognitive impairment (CDR ? 0.5). Results Three-factor interactions between the baseline biomarker values, education, and nWBV were found for Cox proportional hazards models testing tau (p=.03) and ptau (p=.008). Among those with lower tau values, nWBV (hazard ratio [HR]=.54, 95% confidence interval [CI]=.31–.91; p=.02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (p=.01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment among those with higher ptau values (p=.02). In models testing A?42, larger nWBV was associated with a slower time to cognitive impairment (HR=.84, 95%CI=.71–.99, p=.0348), but there was no effect of A?42 or education. Conclusions Among individuals with higher levels of CSF tau and ptau, but normal cognition at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.

Roe, Catherine M.; Fagan, Anne M.; Grant, Elizabeth A.; Marcus, Daniel S.; Benzinger, Tammie L. S.; Mintun, Mark A.; Holtzman, David. M.; Morris, John C.



Thrombin and its precursor in human cerebrospinal fluid.  


The blood coagulation cascade proteolytic enzyme, thrombin, affects many cell types, including neurons and astrocytes, in which it prevents process outgrowth and induces significant morphological degeneration and even cell death. Since thrombin may contribute significantly to pathological conditions in the central nervous system (CNS), where it is synthesized locally, we measured the levels of thrombin and its precursor, prothrombin, in the cerebrospinal fluid (CSF) of 67 individuals from 6 groups: non-neurologic controls (NNC); spinal degenerative disease (SDD); peripheral nerve disease (PND); cerebrovascular, neuroimmune and seizure disorders and tumor (CNSD); traumatic brain injury (TBI) and neurodegenerative disorders (NDD). We employed a sensitive chromogenic assay utilizing the thrombin specific tripeptide substrate, S-2238, to evaluate CSF levels of thrombin and prothrombin. The latter estimated after its conversion to active enzyme by the snake venom prothrombinase, ecarin. No measurable active thrombin was detected in these CSF samples. However, activatable prothrombin was measured in all groups. The mean activatable prothrombin concentrations (in nM) were 7.26 +/- 3.39 (NNC); 8.85 +/- 3.09 (SDD); 6.78 +/- 2.58 (PND); 6.33 +/- 3.87 (CNSD); 5.10 +/- 1.86 (TBI), and 7.80 +/- 3.27 (NDD). Duncan's multiple comparison test showed significant reduction (p <0.05) in prothrombin levels of the TBI group. Our data suggests that the prothrombin zymogen gains access to the CSF, likely across either an intact or compromised blood-brain barrier (BBB), in increased amounts with age. Reduced levels in TBI patients may have diagnostic and/or prognostic value. PMID:9423797

Smirnova, I V; Salazar, A; Arnold, P M; Glatt, S; Handler, M; Festoff, B W



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

SciTech Connect

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

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



Ultrasensitive Stain for Proteins in Polyacrylamide Gels Shows Regional Variation in Cerebrospinal Fluid Proteins  

NASA Astrophysics Data System (ADS)

A new silver stain for electrophoretically separated polypeptides can be rapidly and easily used and can detect as little as 0.01 nanogram of protein per square millimeter. When employed with two-dimensional electrophoresis, it should permit qualitative and quantitative characterization of protein distributions in body fluids and tissues. It has been used to demonstrate regional variations in cerebrospinal fluid proteins.

Merril, Carl R.; Goldman, David; Sedman, Sylvia A.; Ebert, Michael H.



Prostaglandin D Synthase Concentration in Cerebrospinal Fluid and Serum of Patients with Neurological Disorders  

Microsoft Academic Search

Prostaglandin D synthase (PGD synthase) or ?-trace protein is a major constituent of human cerebrospinal fluid (CSF) representing ?3% of the total CSF protein. We have recently developed a highly specific immunofluorometric assay for PGD synthase, which enabled us to quantify the presence of PGD synthase in fluids and tissues not associated with the CNS. In this report we provide

Dimitrios N Melegos; Mark S Freedman; Eleftherios P Diamandis



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


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

Parada, Carolina; Gato, Angel; Bueno, David


Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer's disease.  


Synaptic pathology occurs early in Alzheimer's disease (AD) development, and cerebrospinal fluid biomarkers for synaptic damage may be altered early in the disease process. In the present study we examined cerebrospinal fluid levels of the postsynaptic protein neurogranin in patients with mild cognitive impairment (MCI) or AD and controls. The low neurogranin level in cerebrospinal fluid required enrichment by immunoprecipitation prior to mass spectrometric identification and semi-quantitative immunoblot analysis. Relative quantification revealed a significant increase of neurogranin in the AD group compared with controls, while the MCI group was not statistically different from either controls or the AD group. The concentrations of the AD biomarkers T-tau, P-tau(181) and A?(42) were significantly changed in the control and MCI groups compared with the AD group, but no significant differences were found between the MCI group and controls for the three biomarkers. Nevertheless, a trend towards increasing levels of neurogranin, T-tau and P-tau(181) was found in cerebrospinal fluid from MCI patients compared with controls. The elevated neurogranin levels in the MCI and AD groups might reflect synaptic degeneration. These results together suggest that cerebrospinal fluid neurogranin might be valuable together with the established AD biomarkers in the early diagnosis of AD and warrants further studies to determine the diagnostic value of neurogranin. PMID:20875798

Thorsell, Annika; Bjerke, Maria; Gobom, Johan; Brunhage, Eva; Vanmechelen, Eugeen; Andreasen, Niels; Hansson, Oskar; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj



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


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. PMID:14520657

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



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

PubMed Central

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 in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause.

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



Effects of negatively charged aerosol on blood and cerebrospinal fluid parameters in rats  

NASA Astrophysics Data System (ADS)

Adult male rats were exposed for 90 to 140 minutes to negatively charged tapwater aerosol. Blood and cerebrospinal fluid samples were collected to determine effects of the exposure on selected hematologic and serum chemistry parameters, and ionized calcium and pH in cerebrospinal fluid. Of the 27 variables assayed, 24 yielded sufficient data for statistical analysis. Two parameters, serum alkaline phosphatase and mean corpuscular hemoglobin concentration, were significantly different (p<0.05) from control values, probably representing chance occurrences. It appears that whatever biological effects may be exerted by electro-aerosols, they are not mediated by the parameters investigated in this study.

Wehner, A. P.; Ragan, H. A.; Jaffe, R. A.; Weigel, R. J.; Lundstrom, D. L.



Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis.  


The insulin-like growth factor (IGF) system influences oligodendrocyte survival, myelination, and immune functions. We examined whether alterations in the circulating IGF system occur in multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. We measured concentrations of IGF-I, IGF-II, and insulin-like growth factor binding proteins -1, -2, and -3 in both serum and cerebrospinal fluid from MS patients and age- and sex-matched controls. IGFBP-1 was not detectable in cerebrospinal fluid. We found no significant differences in any of the other components between patients with MS and controls. PMID:9870347

Wilczak, N; Schaaf, M; Bredewold, R; Streefland, C; Teelken, A; De Keyser, J



Pneumocephalus Associated with Cerebrospinal Fluid Fistula as a Complication of Spinal Surgery: A Case Report  

PubMed Central

Pneumocephalus is a well-known condition following head trauma, but is rare as an injury or as a result of surgery of the spine. We present a 76-year-old patient with a rare case of pneumocephalus associated with a cerebrospinal fluid fistula as a complication of surgical treatment for cervical myelopathy. Although cerebrospinal fluid leakage was noted and the injured dura was carefully sutured at operation, tension pneumocephalus occurred. The resultant pneumocephalus was diagnosed based on neurogenic symptoms including sudden convulsion, head radiograph, and computed tomography scan. The benign course of the pneumocephalus postdiagnosis did not require secondary operation.

Sasaki, Ken; Matsumoto, Tomoyuki; Mizuno, Toshiyuki; Ikuta, Shinichi; Akisue, Toshihiro; Fujioka, Hiroyuki; Doita, Minoru; Kurosaka, Masahiro; Kuroda, Ryosuke



Steroid Hormones and Steroid Hormone Binding Globulins in Cerebrospinal Fluid Studied in Individuals with Intact and with Disturbed Blood-Cerebrospinal Fluid Barrier  

Microsoft Academic Search

We measured in simultaneously withdrawn cerebrospinal fluid (CSF) and serum samples from 56 endocrinologically grossly normal patients the concentrations of several lipophilic unconjugated steroids [i.e. dehydroepiandrosterone (DHEA), androstenedione, cortisol, progesterone, testosterone] and their hydrophilic counterparts, i.e. DHEA-sulfate, or hydrophilic binding proteins, i.e. albumin, sex hormone-binding globulin (SHBG) and corticosterone-binding globulin (CBG). CSF levels of total (i.e. free plus protein-bound) DHEA,

Siegfried Schwarz; Peter Pohl



Selenium speciation in paired serum and cerebrospinal fluid samples.  


Se speciation was performed in 24 individual paired serum and cerebrospinal fluid (CSF) samples from neurologically healthy persons. Strong anion exchange (SAX) separation, coupled to inductively coupled plasma-dynamic reaction cell-mass spectrometry (ICP-DRC-MS), was employed. Species identification was done by standard matched retention time, standard addition and by size exclusion chromatography followed from SAX (2-D SEC-SAX-ICP-DRC-MS) and by SAX followed from CE-ICP-DRC-MS (2-D SAX-CE-ICP-DRC-MS). Limit of detection (LoD, 3×standard deviation (SD) of noise) was in the range of 0.026-0.031 ?g/L for all investigated species and thus was set uniformly to 0.032 ?g/L. Quality control for total Se determination was performed by analysing control materials "human serum" and "urine", where determined values met target values. Several Se species were found in both sample types having following median values (sequence: serum/CSF, each in ?g Se/L): total Se, 58.39/0.86; selenoprotein P (SePP), 5.19/0.47; Se-methionine (SeM), 0.23/?65 ?g/L; however, SePP(-CSF) appeared independent of SePP(-serum). For Se-HSA(-serum) versus (vs.) Se-HSA(-CSF), a weak linear relationship was found (r(2)=0.1722). On the contrary, for anti-oxidative Se-enzymes, higher r (2) values were calculated: GPx(-serum) vs. GPx(-CSF), r(2)=0.3837; TrxR(-serum) vs. TrxR(-CSF), r(2)=0.6293. Q(-Se-species) values (= ratios of CSF(-Se-species)/serum(-Se-species)) were compared with the Q (-Alb) value (HSA(-CSF)/HSA(-serum)=clinical index of NB integrity) for deeper information about NB passage of Se species. The Q (-Se-HSA) value (3.8×10(-3)) was in accordance to the molecular mass dependent restriction at NB (Q(-Alb) at 5.25×10(-3)). Increased Q values were seen for TrxR (21.3×10(-3)) and GPx (8.3×10(-3)) which are not (completely) explained by molecular size. For these two anti-oxidative Se-enzymes (GPx, TrxR), we hypothesize that there might be either a facilitated diffusion across NB or they might be additionally synthesized in the brain. PMID:22868477

Solovyev, Nikolay; Berthele, Achim; Michalke, Bernhard



Tau, Phospho-Tau, and S-100B in the Cerebrospinal Fluid of Children With Multiple Sclerosis  

Microsoft Academic Search

Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins

Kevin Rostasy; Esther Withut; Daniela Pohl; Peter Lange; Barbara Ciesielcyk; Ricarda Diem; Jutta Gärtner; Markus Otto



Seizures and retrograde amnesia with cerebrospinal fluid changes following H1N1 influenza vaccination.  


Vaccination against H1N1 influenza of healthcare workers of has been a standard measure to control the epidemic in many countries. Most side effects are minor and transient. Guillain Barre Syndrome and optic neuritis have been major concerns. We report a case of seizures with retrograde amnesia associated with cerebrospinal fluid changes following the H1N1 vaccine. PMID:21840464

Mitrakrishnan, Shivanthan; Ranjanie, Gamage; Thirunavakarasu, Thivakaran; Manjula, Caldera; Nayananjani, Karunasena



[Cerebrospinal fluid serotonin concentration in pyogenic and tick-borne encephalomeningitis].  


Cerebrospinal fluid (CSF) serotonin was determined in 38 patients with pyogenic meningitis and tick-borne encephalitis (TBE) before and after treatment. Increase of CSF serotonin concentration was observed in acute phase of pyogenic meningits and normalized after treatment. PMID:10463248

Siwak, E B; Pawlak, D; Buczko, W; Kondrusik, M; Hermanowska-Szpakowicz, T


Adiponectin and Resistin in Human Cerebrospinal Fluid and Expression of Adiponectin Receptors in the Human Hypothalamus  

Microsoft Academic Search

Context: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier. Objective: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin.

Katarina Kos; Alison L. Harte; Nancy F. da Silva; Anton Tonchev; Georgi Chaldakov; Sean James; David R. Snead; Barbara Hoggart; Joseph P. O'Hare; Philip G. McTernan; Sudhesh Kumar


Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain  

Microsoft Academic Search

Background  The specificity of cerebrospinal fluid (CSF) dynamics in the immature brain still remains unknown. In our data previously published, the transependymal intraparenchymal CSF pathway (the minor pathway) plays a significant role in various degrees in the alternative CSF passage. Now, there is a growing consensus in the age differences in the outcome of neuroendoscopic ventriculostomy in treatment of non-communicating types

Shizuo Oi; Concezio Di Rocco



Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity  

Microsoft Academic Search

Drug transport from the nasal cavity to the brain has gained much interest in the last decade. In the present study, a model was developed to determine the uptake of drugs into the cerebrospinal fluid (CSF) after nasal delivery in rats. CSF samples were taken using a cisternal puncture method. In this method, a needle is advanced through the skin

Mascha P van den Berg; Stefan G Romeijn; J. Coos Verhoef; Frans W. H. M Merkus



Chromogranin A in Cerebrospinal Fluid: A Biochemical Marker for Synaptic Degeneration in Alzheimer’s Disease?  

Microsoft Academic Search

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid

K. Blennow; P. Davidsson; A. Wallin; R. Ekman



Tetranectin is a potential biomarker in cerebrospinal fluid and serum of patients with epilepsy  

Microsoft Academic Search

BackgroundTetranectin (TN) is a plasminogen kringle 4 binding protein and regulates fibrinolysis and proteolytic processes via binding to plasminogen. A previous proteomics study identified TN in the cerebrospinal fluid (CSF) of epileptic patients but not in healthy controls. We determined the concentrations of TN in CSF and serum of epileptic patients to evaluate the changes in TN levels after epileptic

Liang Wang; Yumin Pan; Dan Chen; Zheng Xiao; Zhiqin Xi; Fei Xiao; Xuefeng Wang



Metal Concentrations in Plasma and Cerebrospinal Fluid in Patients with Alzheimer’s Disease  

Microsoft Academic Search

Background\\/Aims: The homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer’s disease (AD). Methods: Concentrations of metals (magnesium, calcium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, cesium, mercury and lead) were determined in plasma and cerebrospinal fluid (CSF) by inductively coupled

Lars Gerhardsson; Thomas Lundh; Lennart Minthon; Elisabet Londos



Cerebrospinal fluid leak associated with nasal continuous positive airway pressure treatment for obstructive sleep apnoea  

Microsoft Academic Search

Clear rhinorrhoea is a common symptom in patients with obstructive sleep apnoea (OSA), which may worsen with nasal continuous positive airway pressure treatment (nCPAP). However, rhinorrhoea can also be the presenting symptom of cerebrospinal fluid (CSF) leak, which is due to a communication between the subarachnoid space and the nasal cavity or sinuses. We report another case of a patient

Jean Yared; Jaafar El Annan



Excitatory Amino Acids in Cerebrospinal Fluid of Patients with Acute Head Injuries  

Microsoft Academic Search

Background: The excitatory amino acids (EAAs) gluta- mate (Glu) and aspartate (Asp) play a role in the pathogenesis of postischemic and posttraumatic brain insult. The changes of EAAs in cerebrospinal fluid (CSF) of patients with traumatic brain injury are incom- pletely understood. Methods: We used reversed-phase HPLC with precol- umn derivatization with o-phthalaldehyde and fluores- cence detection to measure Glu

Zhang Hong; Zhang Xinding; Zhang Tianlin; Chen Liren


Changes in Cerebrospinal Fluid Cytokine Expression in Tuberculous Meningitis Patients with Treatment  

Microsoft Academic Search

Background: The prevalence of tuberculous meningitis (TBM) is very high in developing areas of the world. Inflammation and cytokine patterns produced by T lymphocytes play an important role in susceptibility to infections. The inflammatory response and production of cytokines in the cerebrospinal fluid (CSF) of patients with TBM are well documented. Conversely, little is known about the role of pro-

Rajpal S. Kashyap; Poonam S. Deshpande; Sonali R. Ramteke; Milind S. Panchbhai; Hemant J. Purohit; Girdhar M. Taori; Hatim F. Daginawala



Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients  

Microsoft Academic Search

A new sandwich ELISA is described which shows specificity for tau phosphorylated at threonine 231 and preferentially reacts with Alzheimer's disease (AD) brain extracts relative to other dementias. This assay was used to analyze 58 antemortem cerebrospinal fluid samples. Twenty-three of 27 AD samples (85% sensitivity) yielded signals greater than the cutoff, while only one of 31 non-AD samples (97%

Russell Kohnken; Katharina Buerger; Raymond Zinkowski; Caudill Miller; Daniel Kerkman; John DeBernardis; Jifang Shen; Hans-Jürgen Möller; Peter Davies; Harald Hampel



Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn  

Microsoft Academic Search

Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal fluid examinations from 736 neonates were correlated with clinical diagnosis, treatment, and outcome. The prevalence of fungal or bacterial meningitis in babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity of 68% and a positive predictive value of only 46% for the diagnosis

L Hristeva; I Bowler; R Booy; A King; A R Wilkinson



Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis  

Microsoft Academic Search

We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system (CNS) shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and




Cystatin C in cerebrospinal fluid is not a diagnostic test for pain in humans  

Microsoft Academic Search

A recent subtractive cDNA cloning study in rats demonstrated an unexpected increase in expression of the proteinase inhibitor, cystatin C in the spinal cord during acute peripheral inflammation, suggesting this protein may be involved in the pathogenesis of persistent pain. A subsequent study of 10 women suggested that prolonged labor pain resulted in increased cystatin C concentrations in cerebrospinal fluid,

James C Eisenach; John A Thomas; Richard L Rauck; Regina Curry; Xinhui Li



Desmoid tumor arising around the distal tubing of a cerebrospinal fluid shunt.  


A case of desmoid tumor in the abdominal wall as a cause of malfunction of a cerebrospinal fluid shunt is presented. The desmoid tumor arose from the reactive fibrose tissue formed around the silastic distal tubing and caused the catheter to become disconnected from the reservoir. PMID:2944238

González-Darder, J; Alacreu, J B; Garcia-Vázquez, F



Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple sclerosis  

Microsoft Academic Search

Objective: The diagnosis of multiple sclerosis (MS) can be challenging because of the lack of a specific diagnostic test. Recent advances in proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. Methods: We analyzed cerebrospinal fluid (CSF) samples from 29 patients with MS or clinically isolated syndromes (CIS), 27 patients with transverse myelitis (TM), 50

David N. Irani; Caroline Anderson; Rebekah Gundry; Robert Cotter; Stacy Moore; Douglas A. Kerr; Justin C. McArthur; Ned Sacktor; Carlos A. Pardo; Melina Jones; Peter A. Calabresi; Avindra Nath



Characteristic abnormalities in cerebrospinal fluid biochemistry in children with cerebral malaria compared to viral encephalitis  

Microsoft Academic Search

BACKGROUND: In developing countries where Plasmodium falciparum malaria is endemic, viral encephalitis and cerebral malaria are found in the same population, and parasitemia with Plasmodium falciparum is common in asymptomatic children. The objective of this study was to investigate the cerebrospinal fluid (CSF) biochemistry in children with cerebral malaria compared to those with presumed viral encephalitis. METHODS: We studied the

SR Jakka; S Veena; RM Atmakuri; M Eisenhut



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

Microsoft Academic Search

INTRODUCTION: Macrophage migration inhibitory factor (MIF) plays an essential pathophysiological role in septic shock, but its role in central nervous system infection (CNS) remains to be defined. METHODS: We investigated cerebrospinal fluid (CSF) levels of MIF in 171 patients who were clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis of known aetiology,

Christian Østergaard; Thomas Benfield



MR Measurement of Cerebrospinal Fluid Velocity Wave Speed in the Spinal Canal  

Microsoft Academic Search

Noninvasive measurement of the speed with which the cerebrospinal fluid (CSF) velocity wave travels through the spinal canal is of interest as a potential indicator of CSF system pressure and compliance, both of which may play a role in the development of craniospinal diseases. However, measurement of CSF velocity wave speed (VWS) has eluded researchers primarily due to either a

Wojciech Kalata; Bryn A. Martin; John N. Oshinski; Michael Jerosch-Herold; Thomas J. Royston; Francis Loth



Cerebrospinal fluid corticotropin-releasing hormone in neurodegenerative diseases: Reduction in spinocerebellar degeneration  

Microsoft Academic Search

Levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) were examined in patients with spinocerebellar degeneration (SCD) including olivopontocerebellar atrophy (OPCA), dentatorubropallidoluysian atrophy (DRPLA) and Friedreich's ataxia, Parkinson's disease (PD) and senile dementia of the Alzheimer type (SDAT), and normal aged subjects. CRH concentrations in CSF were significantly reduced in SCD compared to SDAT, PD and normal aged subjects. It

Shuso Suemaru; Koso Suemaru; Kensuke Kawai; Shinji Miyata; Keigo Nobukuni; Yuetsu Ihara; Reiko Namba; Katsuya Urakami; Kozo Hashimoto



Increased Cortisol in the Cerebrospinal Fluid of Women with Functional Hypothalamic Amenorrhea  

Microsoft Academic Search

Context: The proximate cause of functional hypothalamic amenor- rhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast

Benedetta Brundu; Tammy L. Loucks; Lauri J. Adler; Judy L. Cameron; Sarah L. Berga



Cerebrospinal Fluid Tau Levels in Neurodegenerative Diseases with Distinct Tau-Related Pathology  

Microsoft Academic Search

Cerebrospinal fluid tau (CSF-tau) levels were quantified in 8 patients with frontotemporal dementia (FTD), 6 patients with progressive supranuclear palsy (PSP), 3 patients with corticobasal degeneration (CBD), and 6 patients with dementia with Lewy bodies (DLB). The CSF-tau levels were significantly increased in FTD and DLB, but not in PSP and CBD, compared to that previously reported in normal controls.

Hiroyuki Arai; Yu-ichi Morikawa; Makoto Higuchi; Toshifumi Matsui; Christopher M. Clark; Masakazu Miura; Nobuo Machida; Virginia M.-Y. Lee; John Q. Trojanowski; Hidetada Sasaki



Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage  

Microsoft Academic Search

It is crucially important to detect subarachnoid haemorrhage (SAH) in all patients in whom it has occurred to select patients for angiography and preventative surgery. A computerized tomography (CT) scan is positive in up to 98% of patients with SAH presenting within 12 h, but is positive in only 50% of those presenting within one week. Cerebrospinal fluid (CSF) bilirubin

Anne Cruickshank; Peter Auld; Robert Beetham; Gillian Burrows; William Egner; Ian Holbrook; Geoff Keir; Emma Lewis; Dina Patel; I. Watson; P. White



The JC virus antibody response in serum and cerebrospinal fluid in progressive multifocal leucoencephalopathy  

Microsoft Academic Search

Background: A clinical diagnosis of progressive multifocal leucoencephalopathy (PML) can be confirmed by histological or virological examination of brain material. Whilst a less invasive method is provided by the detection of JC DNA in cerebrospinal fluid (CSF), very few studies have been done to assess the value of JC virus (JCV) serology in PML diagnosis.Objectives: To study the JCV antibody

Wendy A. Knowles; Richard W. Luxton; Julian F. Hand; Sylvia D. Gardner; David W. G. Brown



Anisotropic equivalent conductivity tensors for bioelectric modeling of partial volume effects in cerebrospinal fluid spaces  

Microsoft Academic Search

Accurate modeling of bioelectric propagation within the head is necessary for precise electromagnetic source localization. We present here a new approach for modeling spaces fractionally composed of grey matter and cerebrospinal fluid. Using information about the orientation of the cortical surface, we construct anisotropic conductivity tensors to model the partial volume effects frequently present within sulci. Our results indicate that

Damon E. Hyde; Simon K. Warfield



Increase in ?-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome  

Microsoft Academic Search

Background: Individuals with Down syndrome (DS) invariably develop Alzheimer’s disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid-? (A?) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change

Hillevi Englund; Göran Annerén; Jan Gustafsson; Ulrika Wester; Jens Wiltfang; Lars Lannfelt; Kaj Blennow; Kina Höglund



Can Cerebrospinal Fluid Uric Acid Levels Differentiate Intraventricular Hemorrhage from Traumatic Tap?  

Microsoft Academic Search

Objective: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH. Material and Methods: The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved

K. Mutlu Hayran



Epidural fibrin glue injection stops persistent cerebrospinal fluid leak during long-term intrathecal catheterization  

Microsoft Academic Search

he leakage of cerebrospinal fluid (CSF) during the initial phase of long-term intrathecal (IT) in- fusion of analgesics can be a bothersome com- plaint. A series of 98 cancer patients was treated with an IT catheter in this hospital in one year; 8% showed persistent leakage of CSF via the catheter tract. In a previous series, 26% of the patients

Bas M. Gerritse; Robert T. M. van Dongen; Ben J. P. Crul



Prevention of Cerebrospinal Fluid Leaks and Transtemporal Surgery of Acoustic Tumors  

PubMed Central

Postoperative cerebrospinal fluid (CSF) leaks continue to be a problem with transtemporal approaches to the cerebellopontine angle. In this article we describe a modification of the transotic technique, which has proved to be effective in preventing both leaks and subcutaneous collections of CSF. ImagesFigure 5

Kumar, Arvind; Siedentop, Karl H.



Bactericidal Activity against Cephalosporin-ResistantStreptococcus pneumoniaein Cerebrospinal Fluid of Children with Acute Bacterial Meningitis  

Microsoft Academic Search

There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extended- spectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n 511),



Plasma and cerebrospinal fluid pharmacokinetics of SU5416 after intravenous administration in nonhuman primates  

Microsoft Academic Search

Purpose SU5416 is a small, lipophilic synthetic molecule that selectively inhibits the tyrosine kinase activity of the VEGF receptor Flk-1\\/KDR. The role of this agent in brain tumors is currently being investigated. Pharmacokinetic studies of SU5416 have been performed in humans; however, there have been no studies of its penetration in the cerebrospinal fluid (CSF). We studied the pharmacokinetics of

Jamie Renbarger; Alexander Aleksic; Leticia McGuffey; Robert Dauser; Stacey Berg; Susan Blaney



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

Microsoft Academic Search

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

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



Evaluation of Tumor Marker S-100 in Cerebrospinal Fluid from Subjects with Nonischemic Brain Pathologies  

Microsoft Academic Search

In order to evaluate the S-100 concentration in cerebrospinal fluid from subjects with nonischemic brain damage, a total of 33 samples were analyzed: 11 from subjects in whom no organic disease could be found; 14 from patients with a diagnosis of lymphocytic or bacterial-fungal meningitis, and 8 from patients with acute lymphatic leukemia but no demonstrable signs of meningeal involvement.

Jose R. Infante; Miguel Torres-Avisbal; Antonio Martinez; Juan A. Vallejo; Cristobal Aguilera; Pablo Contreras; Ana Benitez; Jose M. Latre



Prolonged Jackson-Pratt drainage in the management of lumbar cerebrospinal fluid leaks  

Microsoft Academic Search

BackgroundCerebrospinal fluid (CSF) leak is a complication of spinal surgery. Intraoperative or postoperative identification of a CSF leak often results in wound healing complications, lumbar drain placement, and\\/or reoperation. These complications usually extend a patient's hospital stay, can be painful, and have their own associated risks. The authors describe a technique that may improve on traditional interventions by managing postoperative

Samuel A. Hughes; Burak M. Ozgur; Michael German; William R. Taylor



Baseline Neuropsychological Profile and Cognitive Response to Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus  

Microsoft Academic Search

Objective: To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). Background: Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure

George Thomas; Matthew J. McGirt; Graeme Woodworth; Jennifer Heidler; Daniele Rigamonti; Argye E. Hillis; Michael A. Williams



Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis  

Microsoft Academic Search

Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of

Ilan Dalal; Sharon Tzhori; Eli Somekh; Avigdor Mandelberg; Arie Levine; Ami Ballin



Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation  

Microsoft Academic Search

Rat cisternal (CSF) hypocretin-1 in cerebrospinal fluid was measured after 6 or 96 h of REM sleep deprivation and following 24 h of REM sleep rebound. REM deprivation was found to increase CSF hypocretin-1 collected at zeitgeber time (ZT) 8 but not ZT0. Decreased CSF hypocretin levels were also observed at ZT8 after 24 h of REM sleep rebound. These

Mario Pedrazzoli; Vania D'almeidasupasu; Paulo J. f. Martins; Ricardo B. Machado; Lin Ling; Seiji Nishino; Sergio Tufik; Emmanuel Mignot



Variables that influence HIV1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis  

Microsoft Academic Search

BACKGROUND: The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF

Diego M Cecchini; Ana M Cañizal; Haroldo Rojas; Alicia Arechavala; Ricardo Negroni; María B Bouzas; Jorge A Benetucci



Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease  

Microsoft Academic Search

Creutzfeldt–Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for

Markus Otto; Jens Wiltfang; Hayrettin Tumani; Inga Zerr; Maria Lantsch; Johannes Kornhuber; Thomas Weber; Hans A Kretzschmar; Sigrid Poser



Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt-Jakob disease  

Microsoft Academic Search

Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses. In a group of 58 patients with definite and probable Creutzfeldt-Jakob disease, NSE concentrations (median 94·0, interquartile range 256 ng\\/mL) were significantly higher (p

I. Zerr; M. Bodemer; S. Räcker; S. Grosche; S. Poser; T. Weber; H. A. Kretzschmar



Plasma and cerebrospinal fluid pharmacokinetics of depsipeptide (FR901228) in nonhuman primates  

Microsoft Academic Search

Purpose Acetylation of histones by histone acetyl transferases (HATs) leads to transcriptional activation, while histone deacetylase (HDAC) activity leads to transcriptional repression. Abnormalities of histone acetylation are associated with the malignant phenotype. Depsipeptide (FR901228) inhibits HDAC and has shown anticancer activity in preclinical models. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of depsipeptide in a nonhuman primate model

Stacey L. Berg; Jeffery Stone; Jim J. Xiao; Kenneth K. Chan; Jed Nuchtern; Robert Dauser; Leticia McGuffey; Patrick Thompson; Susan M. Blaney



Elevation of Cerebrospinal Fluid Protein in Patients with Diabetes Mellitus Is Associated with Duration of Diabetes  

Microsoft Academic Search

We investigated the relationships between total cerebrospinal fluid (CSF) protein in diabetic patients and the clinical characteristics of diabetes mellitus. The subjects comprised 16 diabetic patients (median age = 60.5 years, range = 47–71) who were studied retrospectively. Patients with diseases known to be associated with increases in total CSF protein were excluded as far as possible. The median total

Hiroshi Kobessho; Kenichi Oishi; Hirotoshi Hamaguchi; Fumio Kanda



Polymerase chain reaction (PCR) for rapid detection of cerebrospinal fluid shunt or ventriculostomy infections  

Microsoft Academic Search

Introduction: Infections of cerebrospinal fluid (CSF) shunts or ventriculostomies are common complications that are associated with significant morbidity and mortality. Detection of infection may be difficult or delayed as it requires colonial growth of microorganisms in culture medium. PCR provides rapid and accurate detection of bacterial DNA.Methods: Under Institutional Review Board approval (X030403011), 50 samples of CSF samples were collected

Jason T. Banks; Charles L. Wolff; Suman Bharara; Jeffrey P. Blount; R. Shane Tubbs; G. Yancey Gillespie; James M. Markert



Cerebrospinal fluid biomarkers in Guillain-Barré syndrome – Where do we stand?  

Microsoft Academic Search

\\u000a Abstract\\u000a   Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy affecting the myelin-protein sheathing and the axons\\u000a themselves to various degrees. Damage to these structures causes biomarkers to be released into the adjacent body fluid compartment.\\u000a In case of the proximal nerve roots these biomarkers diffuse into the cerebrospinal fluid (CSF). Here we review the literature\\u000a on CSF biomarkers in GBS,

Johannes Brettschneider; Axel Petzold; Sigurd Süssmuth; Hayrettin Tumani



Management of Persistent Cerebrospinal Fluid Leakage Following Thoraco-lumbar Surgery  

PubMed Central

Study Design This was a retrospective study of patients who had developed a dural tear after thoracic and lumbar spine surgery that was not recognized during the surgery, and was treated either by lumbar drainage or over-sewing of the wounds. Purpose To revisit the treatment strategies in postoperative dural leaks and present our experience with over-sewing of the wound and lumbar drainage. Overview of Literature Unintended durotomy is a frequent complication of spinal surgery. Management of subsequent cerebrospinal fluid leakage remains controversial. There is no distinct treatment guideline according to the etiology in the current literature. Methods The records of 368 consecutive patients who underwent thoracic and/or lumbar spine surgery from 2006 throug h 2010 were retrospectively reviewed. Seven cerebrospinal fluid fistulas and five pseudomeningoceles were noted in 12 (3.2%) procedures. Cerebrospinal fluid diversion by lumbar drainage in five pseudomeningoceles and over-sewing of wounds in seven cerebrospinal fluid fistulas employed in 12 patients. Clinical grading was evaluated by Wang. Results Of the 12 patients who had a dural tear, 5 were managed successfully with lumbar drainage, and 7 with oversewing of the wound. The clinical outcomes were excellent in 9 patients, good in 2, and poor in 1. Complications such as neurological deficits, or superficial or deep wound infections did not develop. A recurrence of the fistula or pseudomeningocele after the treatment was not seen in any of our patients. Conclusions Pseudomeningoceles respond well to lumbar drainage, whereas over-sewing of the wound is an alternative treatment option in cerebrospinal fluid fistulas without neurological compromise.

Ilbay, Konuralp; Kim, Michael Sun Min; Selek, Ozgur



Ventriculoperitoneal shunt malfunction from cerebrospinal fluid eosinophilia in children: case-based update  

Microsoft Academic Search

Introduction  Malfunction of cerebrospinal shunts is common and is due to multiple etiologies ranging from obstruction due to infiltrated\\u000a brain tissue to mechanical disconnection.\\u000a \\u000a \\u000a \\u000a \\u000a Discussion  We review the differential diagnosis and recommended evaluation and treatment for cerebrospinal fluid (CSF) eosinophilia.\\u000a \\u000a \\u000a \\u000a Illustrative case  We report a child who, following the use of an antibiotics-impregnated ventricular catheter, developed sterile ventriculoperitoneal\\u000a shunt malfunction thought to be

R. Shane Tubbs; Mitchel Muhleman; Marios Loukas; Aaron A. Cohen-Gadol


Cerebrospinal fluid creatine kinase in acutely psychotic patients 1  

PubMed Central

Significantly elevated serum creatine phosphokinase concentrations have been demonstrated in 70% of patients with acute psychosis. Elevations in spinal fluid creatine phosphokinase (CPK) activity have been reported in several neurological diseases, often in association with otherwise normal routine spinal fluid studies. Spinal fluid and serum were obtained simultaneously from 11 patients with acute psychosis, the majority being schizophrenic. Although the serum CPK was elevated in eight of the 11 subjects, spinal fluid glucose, protein, colloidal gold, and CPK were normal in all cases. The theoretical implications of these results are discussed.

Martin, William A.; Garey, Richard E.; Heath, Robert G.



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


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

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



A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases*  

PubMed Central

Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as ?? crystallin, enolase, and 14–3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin response mediator protein-2 was increased, whereas Ubiquitin carboxy-terminal hydrolase L1 was down-regulated, not only highlights the importance of these molecules in the pathology of this disease, but also illustrates the use of our approach in attempting to decipher the complex pathological processes leading to multiple sclerosis and other neurodegenerative diseases.

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



Use of cerebrospinal fluid biomarkers in clinical trials for schizophrenia and depression.  


The pharmaceutical industry is increasingly using biomarkers in clinical trials in order to determine if new drug candidates are displaying the expected pharmacological properties and to give early indications if they are showing efficacy or unexpected toxicity. This is especially true for the development of new drug candidates for psychiatric disorders such as schizophrenia and depression, where it is imperative to understand whether the drug is reaching the brain and acting on the target. A particular challenge for biochemical biomarkers used to determine centrally mediated activity is the relative inaccessibility of the brain to direct sampling of cells or tissues. As a result, the use of biomarkers located in the cerebrospinal fluid and in close contact with the interstitial fluid of the brain has risen in prominence. Cerebrospinal fluid biomarkers allow for the analysis of biochemical changes that reflect pharmacological activity or that may be related to the disease. In the area of psychiatric disorders, many studies have utilized biochemical biomarkers in the cerebrospinal fluid for gaining pharmacodynamic or disease modification information. This review summarizes many of these efforts, and identifies challenges and opportunities for utilizing biomarkers for new drug candidates targeting psychiatric disorders. PMID:22296205

Wan, Hong I; Soares, Holly; Waring, Jeffrey F



Burr Hole Drainage : Could Be Another Treatment Option for Cerebrospinal Fluid Leakage after Unidentified Dural Tear during Spinal Surgery?  

PubMed Central

Authors report a rare case of acute intracranial subdural and intraventricular hemorrhage that were caused by intracranial hypotension resulted from cerebrospinal fluid leakage through an unidentified dural tear site during spinal surgery. The initial brain computed tomography image showed acute hemorrhages combined with preexisting asymptomatic chronic subdural hemorrhage. One burr hole was made over the right parietal skull to drain intracranial hemorrhages and subsequent drainage of cerebrospinal fluid induced by closure of the durotomy site. Among various methods to treat cerebrospinal fluid leakage through unidentified dural injury site, primary repair and spinal subarachnoid drainage are well known treatment options. The brain imaging study to diagnose intracranial hemorrhage should be taken before selecting the treatment method, especially for spinal subarachnoid drainage. Similar mechanism to its spinal counterpart, cranial cerebrospinal fluid drainage has not been mentioned in previous article and could be another treatment option to seal off an unidentified dural tear in particular case of drainage of intracranial hemorrhage is needed.



Stanthrdization of theCoomassie BlueMethodforCerebrospinal FluidProteins  

Microsoft Academic Search

Coomassie Brilliant Blue G-250 can be used to quantita- tively determine proteins in cerebrospinal fluid. Whenthe dye combines with protein, the absorption maximum of the dye shifts. The dye-protein color forms almost instanta- neously and is stable for at least 1 h. The procedure is also insensitive to changes in temperature in the range of 20-30 #{176}C. The absorptivities of



2?, 3?Cyclic nucleotide 3?-phosphodiesterase activity in the cerebrospinal fluid of patients with demyelinating diseases  

Microsoft Academic Search

We aimed to study the level of CNPase activity in the cerebrospinal fluid of patients with demyelinating diseases and other\\u000a neurological diseases, particularly multiple sclerosis, with reference to CSF myelin basic protein content. CNPase activity\\u000a was measured paper chromatographically using radioactive 2?,3?-cAMP as a substrate. Myelin basic protein content was measured\\u000a with a radioimmunoassay. The mean level of CNPase activity

Haruhiko Suda; Takeshi Hosokawa; Ryozo Ohno; Kastuhiko Hamaguchi; Yasuzo Tsukada



Neopterin and biopterin concentrations in cerebrospinal fluid in controls less than 1 year old  

Microsoft Academic Search

Neopterin and biopterin concentrations were measured in cerebrospinal fluid (CSF) and urine samples from controls less than 1 year old. This is the first time for CSF reference data for controls less than 1 year old to be reported. The ratio of neopterin to biopterin in CSF 0–30 days (n=48) of age in control samples was 0.65±0.31 (SD), which was

Yoshitomo Sawada; Haruo Shintaku; Gen Isshiki



Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations  

Microsoft Academic Search

Background: The diagnosis of pediatric neurologic disorders with a deficiency in the biosynthesis of either the neurotransmitters serotonin and dopamine, or the co-factor tetrahydrobiopterin or a cerebral 5-methyltetrahydrofolate (5-MTHF) deficiency, strongly relies on a robust analysis of neurotransmitter metabolites, pterins and 5-MTHF in the cerebrospinal fluid (CSF). The aim of this study was to investigate which technical and biochemical factors

M. M. Verbeek; A. M. Blom; R. A. Wevers; A. J. Lagerwerf; J. van de Geer; M. A. A. P. Willemsen



Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome  

Microsoft Academic Search

BackgroundNeurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.Methods and Principal FindingsPooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry

Steven E. Schutzer; Thomas E. Angel; Tao Liu; Athena A. Schepmoes; Therese R. Clauss; Joshua N. Adkins; David G. Camp; Bart K. Holland; Jonas Bergquist; Patricia K. Coyle; Richard D. Smith; Brian A. Fallon; Benjamin H. Natelson; Howard Gendelman



Detection of cancer cells in the cerebrospinal fluid: current methods and future directions  

Microsoft Academic Search

The spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality.\\u000a The current tools available for detecting the spread of cancer into the cerebrospinal fluid (CSF) are cytology, neurologic\\u000a examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer\\u000a from

Cody L Weston; Michael J Glantz; James R Connor



Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis  

Microsoft Academic Search

BackgroundAdjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone.Methodology\\/Principal FindingsThe kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations

Justin A. Green; Chau T. H. Tran; Jeremy J. Farrar; Mai T. H. Nguyen; Phu H. Nguyen; Sinh X. Dinh; Nghia D. T. Ho; Chuong V. Ly; Hien T. Tran; Jon S. Friedland; Guy E. Thwaites



Cerebrospinal fluid proteomic patterns discriminate Parkinson's disease and multiple system atrophy.  


The differential diagnosis of Parkinson's disease and multiple system atrophy can be challenging, especially in the early stages of the diseases. We developed a proteomic profiling strategy for parkinsonian diseases using mass spectrometry analysis for magnetic-bead-based enrichment of cerebrospinal fluid peptides/proteins and subsequent multivariate statistical analysis. Cerebrospinal fluid was obtained from 37 patients diagnosed with Parkinson's disease, 32 patients diagnosed with multiple system atrophy, and 26 patients diagnosed with other neurological diseases as controls. The samples were from the first cohort and the second cohort. Cerebrospinal fluid peptides/proteins were purified with C8 magnetic beads, and spectra were obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Principal component analysis and support vector machine methods are used to reduce dimension of the data and select features to classify diseases. Cerebrospinal fluid proteomic profiles of Parkinson's disease, multiple system atrophy, and control were differentiated from each other by principal component analysis. By building a support vector machine classifier, 3 groups were classified effectively with good cross-validation accuracy. The model accuracy was well preserved for both cases, training by the first cohort and validated by the second cohort and vice versa. Receiver operating characteristics proved that the peak of m/z 6250 was the most important to differentiate multiple system atrophy from Parkinson's disease, especially in the early stages of the disease. A proteomic pattern classification method can increase the accuracy of clinical diagnosis of Parkinson's disease and multiple system atrophy, especially in the early stages. PMID:22674850

Ishigami, Noriko; Tokuda, Takahiko; Ikegawa, Masaya; Komori, Mika; Kasai, Takashi; Kondo, Takayuki; Matsuyama, Yumiko; Nirasawa, Takashi; Thiele, Herbert; Tashiro, Kei; Nakagawa, Masanori



Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt–Jakob disease  

Microsoft Academic Search

Objective: To determine the concentrations of microtubule associated protein tau and multiple phosphorylated tau epitopes in the cerebrospinal fluid of patients with sporadic Creutzfeldt–Jakob disease (sCJD), dementias, and controls, in order to evaluate their diagnostic use and clinical relevance.Methods: The CSF concentrations of total tau and phosphorylated tau at epitope 181 were determined by enzyme linked immunosorbent assay in 66

B Van Everbroeck; A J E Green; E Vanmechelen; H Vanderstichele; P Pals; R Sanchez-Valle; N Cuadrado Corrales; J-J Martin; P Cras



Peptide repertoire of human cerebrospinal fluid: novel proteolytic fragments of neuroendocrine proteins  

Microsoft Academic Search

Polypeptides in human cerebrospinal fluid (CSF), isolated by phase separation in chloroform–methanol–water and reversed-phase HPLC, were characterised by sequence analysis and mass spectrometry. This identified the presence of peptide fragments of testican, neuroendocrine specific protein VGF, neuroendocrine protein 7B2, chromogranin B\\/secretogranin I, chromogranin A, osteopontin, IGF-II E-peptide and proenkephalin. The majority of these fragments were generated by proteolysis at dibasic

Margareta Stark; Olle Danielsson; William J. Griffiths; Hans Jörnvall; Jan Johansson



Phytoestrogens and thyroid hormone levels in the cerebrospinal fluid of ewes fed red clover silage  

Microsoft Academic Search

In sheep, phytoestrogens are known to act at various levels on the hypothalamo–pituitary–gonadal axis, as well as the hypothalamo–pituitary–thyroid axis. The levels of genistein and daidzein and their metabolites, p-ethylphenol and equol, in the cerebrospinal fluid (CSF) were studied in ewes fed red clover silage. Moreover, to test the hypothesis that phytoestrogens may affect the access of thyroid hormones in

J. Skipor; T. Misztal; M. Pisku?a; W. Wiczkowski; J.-C. Thiéry


Failure of cerebrospinal fluid shunts: part II: overdrainage, loculation, and abdominal complications.  


Complications from cerebrospinal fluid shunts are common and can present with a variety of signs and symptoms. In this second part of a two-part review, shunt overdrainage, loculation of the ventricular system in patients with shunts, and abdominal complications related to ventriculoperitoneal shunts are discussed. Familiarity with these types of shunt failure is essential for neurologists and pediatricians because they are often the first to evaluate and triage these children. PMID:16504785

Browd, Samuel R; Gottfried, Oren N; Ragel, Brian T; Kestle, John R W



Clinical significance of cerebrospinal fluid nitric oxide concentrations in degenerative cervical and lumbar diseases  

Microsoft Academic Search

In animal models of degenerative lumbar disease, inducible nitric oxide synthase (iNOS) is expressed in macrophages and Schwann\\u000a cells following compression of the cauda equina. We previously reported that NO metabolites (nitrite plus nitrate: [NOx])\\u000a in the cerebrospinal fluid (CSF) correlate with postoperative pain relief in patients with degenerative lumbar disease and\\u000a with neurologic recovery rate postoperatively or after conservative

Hiroshi Denda; Shinji Kimura; Akiyoshi Yamazaki; Noboru Hosaka; Yuichi Takano; Kenji Imura; Yoichi Yajiri; Naoto Endo



Evaluation of Cerebrospinal Fluid Tau\\/Beta-Amyloid(42) Ratio as Diagnostic Markers for Alzheimer Disease  

Microsoft Academic Search

Background: Alzheimer’s disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. Cerebrospinal fluid (CSF) concentrations of amyloid ? (A?1-42) peptides and total tau proteins (T-tau) may serve as biomarkers for AD. Aim: The objective of this study was to investigate the usefulness of CSF A?1-42 and T-tau analyses in the diagnosis of AD

Mohamed Ali Smach; Bassem Charfeddine; Leila Ben Othman; Turkia Lammouchi; Hedi Dridi; Souhir Nafati; Afef Ltaief; Soufien Bennamou; Khalifa Limem



No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia  

Microsoft Academic Search

Tau protein levels in cerebrospinal fluid (CSF-tau) were determined in 29 patients with old cerebrovascular disease (CVD, 21 demented and eight non-demented), 69 patients with Alzheimer's disease (AD) and 17 age-matched normal controls. The CSF-tau level in the vascular dementia (VD) group (24.0±17.0 pg\\/ml) was significantly lower (P<0.0001) than that in the AD group (90.0±45.3 pg\\/ml), but not significantly different

Hiroyuki Arai; Takuma Satoh-Nakagawa; Makoto Higuchi; Yu-ichi Morikawa; Masakazu Miura; Hisako Kawakami; Hisatomo Seki; Sadao Takase; Hidetada Sasaki



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

Microsoft Academic Search

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

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



Neuronal targets of serum and cerebrospinal fluid autoantibodies in amyotrophic lateral sclerosis  

Microsoft Academic Search

Sera and cerebrospinal fluid (CSF) from 25 patients with amyotrophic lateral sclerosis (ALS) were tested by immunofluorescence\\u000a on fetal, juvenile and adult central and peripheral neuronal (CNS\\/PNS) tissues and on nerve biopsy material from affected\\u000a patients for the presence of autoantibodies. Results were compared with control sera from normal blood donors (n = 45) and patients with other neurological diseases

Axel Greiner; Bernd Schmaußer; Klaus Petzold; Hans Krüger; Alexander Marx



Tamoxifen Paradoxically Decreases Paclitaxel Deposition into Cerebrospinal Fluid of Brain Tumor Patients  

Microsoft Academic Search

Summary  Background: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the\\u000a available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in\\u000a human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component\\u000a of the blood–cerebrospinal fluid

Johnson Chen; Casilda Balmaceda; Jeffrey N. Bruce; Michael B. Sisti; May Huang; Ying Kuen K. Cheung; Guy M. McKhann; Robert R. Goodman; Robert L. Fine



Proteome analysis of cerebrospinal fluid in Guillain–Barré syndrome (GBS)  

Microsoft Academic Search

We used two-dimensional difference in-gel electrophoresis (2-D-DIGE) for proteome analysis of cerebrospinal fluid (CSF) in Guillain–Barré syndrome (GBS). Spots showing >2-fold difference between GBS and controls were analysed using MALDI-TOF mass spectrometry.Proteins that were up-regulated in GBS included haptoglobin, serine\\/threonine kinase 10, ?-1-antitrypsin, SNC73, alpha II spectrin, IgG kappa chain and cathepsin D preprotein, while transferrin, caldesmon, GALT, human heat

V. Lehmensiek; S. D. Süssmuth; J. Brettschneider; G. Tauscher; S. Felk; F. Gillardon; H. Tumani



The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A)  

Microsoft Academic Search

Objectives: Biological markers of narcolepsy with cataplexy (classical narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF) hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF leptin. The clinical borderland of narcolepsy and the diagnostic value of different markers of narcolepsy remain controversial and were

Claudio Bassetti; Matthias Gugger; Matthias Bischof; Johannes Mathis; Christian Sturzenegger; Esther Werth; Bogdan Radanov; Beth Ripley; Seiji Nishino; Emmanuel Mignot



Central Nervous System Toxicity and Cerebrospinal Fluid Pharmacokinetics of Intraventricularly Administered Bleomycin in Beagles1  

Microsoft Academic Search

The neurotoxic effects and cerebrospinal fluid (CSF) pharma- cokinetics of bleomycin were evaluated in beagles after chronic intraventricular administration twice a week for 8 consecutive weeks. Bleomycin was reasonably well tolerated at doses of 0.067 to 0.3 mg\\/week. Doses higher than 0.3 mg\\/week produced marked elevation of CSF protein levels and a necrotizing vas- culitis within the central nervous system.

Victor A. Levin; Deborah Byrd; Branimir I. Sikic; B. Bill Etiz; Julia Campbell; Janice K. Bereich; Richard L. Davis


DNA single cell cytometry in lymphocytic pleocytosis of the cerebrospinal fluid  

Microsoft Academic Search

The value of DNA single-cell cytometry for the detection of neoplasia in Feulgen-stained cerebrospinal fluid cytological specimens was tested on 34 cases of Non-Hodgkin's lymphoma or leukemia and on 66 cases of viral or bacterial meningitis as a disease control group. The DNA content of 200 randomly chosen nuclei was measured on one pre-existing, cytologically representative slide per case, using

Stefan Biesterfeld; Bettina Bernhard; Stephan Bamborschke; Alfred Böcking



Kearns-Sayre syndrome: Cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features  

Microsoft Academic Search

We evaluated cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF), biogenic amines, and white matter status in six Kearns-Sayre syndrome (KSS) patients. They presented severe 5-MTHF deficiency. A significant negative correlation was observed between CSF 5-MTHF and protein concentration. CSF homovanillic acid was clearly high. Regarding neuroimaging, the main feature was hyperintensity in the basal ganglia, brainstem, and cerebral\\/cerebellar white matter. The severity

Mercedes Serrano; María Teresa García-Silva; Elena Martin-Hernandez; Maria del Mar O’Callaghan; Pilar Quijada; Ana Martinez-Aragón; Aida Ormazábal; Alberto Blázquez; Miguel A. Martín; Paz Briones; Ester López-Gallardo; Eduardo Ruiz-Pesini; Julio Montoya; Rafael Artuch; Mercedes Pineda



Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer's disease  

Microsoft Academic Search

Cerebrospinal fluid (CSF) concentrations of tau protein were measured using an enzyme-linked immunosorbent assay which measures both normal and hyperphosphorylated tau. Levels of CSF tau were measured in 17 patients with Alzheimer's disease and 23 patients with frontotemporal dementia, and were compared to age-matched healthy controls. The CSF tau concentration in control subjects was 198±49 pg\\/ml and no relationship was

A. J. E Green; R. J Harvey; E. J Thompson; M. N Rossor



New PCR assay for rapid and quantitative detection of human cytomegalovirus in cerebrospinal fluid.  

PubMed Central

Rapid Chelex extraction combined with an automated hybridization assay for the detection of PCR-amplified human cytomegalovirus DNA from cerebrospinal fluid was established. Quantitation of DNA was performed with a plasmid being used as an external standard. The detection limit was 10 copies per microliter. Quantitative detection of human cytomegalovirus DNA could be achieved over a range from 10 to 10(4) copies per microliter.

Vogel, J U; Cinatl, J; Lux, A; Weber, B; Driesel, A J; Doerr, H W



Pediatric Neurosurgical Practice Patterns Designed to Prevent Cerebrospinal Fluid Shunt Infection  

Microsoft Academic Search

Background\\/Aims: Various factors have been associated with cerebrospinal fluid (CSF) shunt infection risk, leading to many recommendations intended to reduce that risk. We sought to assess current North American pediatric neurosurgical practice patterns in this regard via a web-based survey. Particular attention was paid to the use of antibiotic-impregnated materials and prophylactic perioperative antibiotics. Methods: The membership of the section

Thomas J. Gruber; Sara Riemer; Curtis J. Rozzelle



Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica  

Microsoft Academic Search

Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1#, IL-6, IL-8, interferon (IFN)-% and tumour necrosis factor (TNF)-! were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar

H. Brisby; K. Olmarker; K. Larsson; M. Nutu; B. Rydevik



Determination of haem derivatives in the cerebrospinal fluid--a semi-quantitative method.  

PubMed Central

A spectrophotometric method for semi-quantitative determination of oxyhaemoglobin, methaemoglobin and bilirubin in the cerebrospinal fluid is described and evaluated. The method involves correction for CSF protein. It is based on absorbance registrations on three wavelengths; 400, 420 and 470 nm. Reference values for a healthy control group and a hyperbilirubinaemic group are presented. Evaluation of the method shows that it is well suited to semi-quantitative determination of haem derivatives in the CSF.

Wahlgren, N G; Bergstrom, K



Plasma and cerebrospinal fluid pharmacokinetics of SU5416 after intravenous administration in nonhuman primates  

Microsoft Academic Search

Purpose: SU5416 is a small, lipophilic synthetic molecule that selectively inhibits the tyrosine kinase activity of the VEGF receptor\\u000a Flk-1\\/KDR. The role of this agent in brain tumors is currently being investigated. Pharmacokinetic studies of SU5416 have\\u000a been performed in humans; however, there have been no studies of its penetration in the cerebrospinal fluid (CSF). We studied\\u000a the pharmacokinetics of

Jamie Renbarger; Alexander Aleksic; Leticia McGuffey; Robert Dauser; Stacey Berg; Susan Blaney



Cerebrospinal fluid Tau/?-synuclein ratio in Parkinson's disease and degenerative dementias.  


Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, A?(1-42) , total tau, phosphorylated tau, and ?-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. A?(1-42) , total tau, phosphorylated tau, and ?-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean ?-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of ?-synuclein with total tau (r = -0.196, P < .01) was observed. In the group of patients with Parkinson's disease, A?(1-42) , total tau, and phosphorylated tau values were similar to controls, whereas total tau/?-synuclein and phosphorylated tau/?-synuclein ratios showed the lowest values. Cerebrospinal fluid ?-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/?-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of ?-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/?-synuclein and phosphorylated tau/?-synuclein ratios can contribute to the discrimination of Parkinson's disease. © 2011 Movement Disorder Society. PMID:21469206

Parnetti, Lucilla; Chiasserini, Davide; Bellomo, Gianni; Giannandrea, David; De Carlo, Claudia; Qureshi, Mohamed M; Ardah, Mustafa T; Varghese, Shiji; Bonanni, Laura; Borroni, Barbara; Tambasco, Nicola; Eusebi, Paolo; Rossi, Aroldo; Onofrj, Marco; Padovani, Alessandro; Calabresi, Paolo; El-Agnaf, Omar



Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis  

Microsoft Academic Search

To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from

Violaine K. Harris; Andrew Diamanduros; Pamela Good; Elina Zakin; Varun Chalivendra; Saud A. Sadiq



Infection of Cerebrospinal Fluid Shunts: Causative Pathogens, Clinical Features, and Outcomes  

Microsoft Academic Search

SUMMARY: This retrospective chart review describes the clinical features, pathogens, and outcomes of 46 patients with cerebrospinal fluid (CSF) shunt infections collected over 16 years. The overall CSF shunt infection rate was 2.1%, broken down into 1.7 and 9.3% in adult and pediatric groups, respectively. Fever and progressive consciousness disturbance were the most prominent clinical features in the adult patient

Kuo-Wei Wang; Wen-Neng Chang; Teng-Yuan Shih; Chi-Ren Huang; Nai-Wen Tsai; Chen-Sheng Chang; Yao-Chung Chuang; Po-Chou Liliang; Thung-Ming Su; Cheng-Shyuan Rau; Yu-Duan Tsai; Ben-Chung Cheng; Pi-Lien Hung; Chin-Jung Chang; Cheng-Hsien Lu


Oxidative Stress in Cerebrospinal Fluid of Patients with Aseptic and Bacterial Meningitis  

Microsoft Academic Search

This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress\\u000a parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status\\u000a has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS)\\u000a and antioxidant defense systems such as superoxide

Charlene Cavalheiro de Menezes; Aracélli Gnatta Dorneles; Rita Leal Sperotto; Marta Medeiros Frescura Duarte; Maria Rosa Chitolina Schetinger; Vania Lúcia Loro



Cerebrospinal Fluid Amyloid ? 1–42 Levels in the Mild Cognitive Impairment Stage of Alzheimer's Disease  

Microsoft Academic Search

Cerebrospinal fluid (CSF) levels of amyloid ?-protein ending at amino acid position 42 (CSF-A ?1–42) and CSF-tau levels were quantified by sandwich ELISAs in 19 patients with mild cognitive impairment (MCI) who eventually developed Alzheimer's disease (AD) on follow-up as well as in 15 age-matched normal controls and 54 AD patients at diverse stages of the disease. In the present

Masahiro Maruyama; Hiroyuki Arai; Mitsunori Sugita; Haruko Tanji; Makoto Higuchi; Nobuyuki Okamura; Toshifumi Matsui; Susumu Higuchi; Sachio Matsushita; Hiroshi Yoshida; Hidetada Sasaki



The molecular forms of acetylcholinesterase in cerebrospinal fluid of normal subjects — effect of aging  

Microsoft Academic Search

Summary Acetylcholinesterase (AChE) activity is increased in human cerebrospinal fluid (CSF) during aging. The present study investigated whether the relative amounts of different molecular forms of CSF-AChE are also affected during aging. Thus, the CSF samples of healthy human subjects (age range 20–79 years, n=23) were analyzed for sedimentation forms of AChE activity. Five different forms of AChe activity were

J. Sirviii; Z. Rakonczay; P. Hartikainen; P. Kasa; P. J. Riekkinen



Intracranial Hypotension Caused by Cervical Cerebrospinal Fluid Leak: Treatment with Epidural Blood Patch  

Microsoft Academic Search

This report describes treatment with cervical epidural blood patch of low cerebrospinal fluid (CSF) pressure headache resulting from spontaneous CSF leak via a tear in a cervical dural cuff. The leak was diagnosed by a dynamic computed tomography (CT)-myelography study followed by gadolinium enhanced magnetic res- onance imaging(MRI)-scan. The epidural needle was inserted with the aid of image intensifier and

Michael J. Cousins; David Brazier; Raymond Cook



5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid  

Microsoft Academic Search

ACCORDING to the serotonin (5-hydroxytryptamine, 5-HT) hypothesis there is a causal relationship between mental depression and 5-HT deficiency in the brain1-3. Some depressive patients-mainly those suffering from an endogenous depression-display the following clinical signs. (1) The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) (refs. 4 and 5) and the urinary concentrations of 5-HT (ref. 6) and 5-HIAA

H. M. van Praag; J. Korf; J. Puite



Polyclonal B-Cell Expansion in the Cerebrospinal Fluid of Patients with Psedotumor Cerebri  

Microsoft Academic Search

To investigate the hypothesis that pseudotumor cerebri (PTC) is associated with humoral immunity, we analyzed immunoglobulin heavy chain variable region (Ig-VH) genes of B cells in the cerebrospinal fluid (CSF) of 10 patients with PTC. Using RT-PCR and sequencing techniques, intrathecal B-cell Ig-VH genes were amplified in 6 of 10 PTC samples. Sequence analysis of complementarity-determining region 3 (CDR 3)




Cerebrospinal fluid (CSF) and serum S100B: release and wash-out pattern  

Microsoft Academic Search

S100B is an important brain specific protein for monitoring damage and activation of astrocytes. Using a straight forward, non-resource demanding in-house ELISA technique we measured S100B in cerebrospinal fluid (CSF) and serum in patients with traumatic brain injury (TBI) (serum), subarachnoid hemorrhage (SAH) (CSF, serum), intracranial hemorrhage (ICH) (CSF, serum), normal controls (NC) (serum) and a reference population (CSF, N=409).

A. Petzold; G. Keir; D. Lim; M. Smith; E. J. Thompson



Treatment of Cerebrospinal Fluid Shunting Complications in a Nigerian Neurosurgery Programme  

Microsoft Academic Search

Background\\/Aims: For a century since the first cerebrospinal fluid (CSF) shunt surgery, ventriculoperitoneal (VP) shunt insertion for the treatment of hydrocephalus has routinely been performed. A lot of common and rare complications following this procedure have been reported in 24–47% of the cases. The aim of this paper was to present our experience with the treatment of hydrocephalus in our

Edward O. Komolafe; Augustine A. Adeolu; Morenikeji A. Komolafe



S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease  

Microsoft Academic Search

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the\\u000a German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective\\u000a case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive\\u000a dementia

Markus Otto; Holger Stein; Annemarie Szudra; Inga Zerr; Monika Bodemer; Olaf Gefeller; Sigrid Poser; Hans A. Kretzschmar; Michael Mäder; Thomas Weber



Quantification of poly(ADP-ribose)-modified proteins in cerebrospinal fluid from infants and children after traumatic brain injury  

Microsoft Academic Search

Poly-ADP-ribosylation (PAR) of proteins by poly(ADP-ribose) polymerases (PARP) occurs after experimental traumatic brain injury (TBI) and modulates neurologic outcome. Several promising pharmacological PARP inhibitors have been developed for use in humans, but there is currently no clinically relevant means of monitoring treatment effects. We therefore used an enzyme-linked immunosorbent assay to measure PAR-modified proteins in cerebrospinal fluid (CSF). Cerebrospinal fluid

Ericka L Fink; Yichen Lai; Xiaopeng Zhang; Keri Janesko-Feldman; P David Adelson; Csaba Szabó; Rachel P Berger; Ajit A Sarnaik; Patrick M Kochanek; Robert S B Clark; RSB Clark



Peripheral neuroactive steroids may be as good as the steroids in the cerebrospinal fluid for the diagnostics of CNS disturbances  

Microsoft Academic Search

To compare the predictivity of the neuroactive steroids in the cerebrospinal fluid and peripheral blood for the diagnostics of CNS disturbances, eighteen unconjugated steroids were quantified in the cerebrospinal fluid (CSF) from the 3rd ventricle and 18 unconjugated steroids and 7 steroid polar conjugates were measured in the serum using GC–MS and RIA. Eight postmenopausal women (56–78 years of age)

Radmila Kancheva; Martin Hill; Zden?k Novák; Jan Chrastina; Marta Velíková; Lyudmila Kancheva; Ivo ?íha; Luboslav Stárka



Development of a theoretical framework for analyzing cerebrospinal fluid dynamics  

PubMed Central

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 conservation; but control volume analysis enforces independent conditions on pressure and volume. Previously, utilization of clinical measurements has been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Methods Control volume analysis is presented to introduce the reader to the theoretical background of this foundational fluid mechanics technique for application to general control volumes. This approach is able to directly incorporate the diverse measurements obtained by clinicians to better elucidate intracranial dynamics and progression to disorder. Results Several examples of meaningful intracranial control volumes and the particular measurement sets needed for the analysis are discussed. Conclusion Control volume analysis provides a framework to guide the type and location of measurements and also a way to interpret the resulting data within a fundamental fluid physics analysis.

Cohen, Benjamin; Voorhees, Abram; Vedel, S?ren; Wei, Timothy



Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis.  


Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of a single viral agent and to correlate between cytokine levels and leukocytes. Cerebrospinal fluid samples, collected during an outbreak of echovirus type 4 meningitis in infants and children in Israel, were tested for routine characteristics. In addition, cytokine levels were measured in 71 meningitis patients and compared with those of 11 nonmeningitis patients. Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P < 0.01) and interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P < 0.01) were significantly higher in patients with meningitis than in the control group, whereas soluble intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did not differ significantly. In addition, only interleukin-6 levels correlated with leukocyte counts in viral meningitis patients. Interleukin-6 was the most sensitive and specific characteristic in predicting meningitis in this homogeneous group of patients. Furthermore, only interleukin-6 correlated with leukocyte counts in the cerebrospinal fluid. PMID:14643393

Dalal, Ilan; Tzhori, Sharon; Somekh, Eli; Mandelberg, Avigdor; Levine, Arie; Ballin, Ami



Radioimmunoassay of serotonin (5-hydroxytryptamine) in cerebrospinal fluid, plasma, and serum  

SciTech Connect

A direct radioimmunoassay is described for serotonin (5-hydroxytryptamine) in cerebrospinal fluid, platelet-poor plasma, and serum. Antisera in rabbits was raised against serotonin diazotized to a conjugate of bovine albumin and D,L-p-aminophenylalanine. Polyethylene glycol, alone or in combination with anti-rabbit immunoglobulins, is used to separate bound and unbound tritiated serotonin. The minimum concentration of serotonin detectable is 2 nmol/L in a sample. Within-day precision (CV) is 4.3% between-day precision 7.7%. Analytical recoveries of serotonin are 109% and 101% for cerebrospinal fluid and plasma, respectively. Tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol do not interfere with the assay. However, 5-methoxytryptamine and tryptamine cross react. Of samples of cerebrospinal fluid from patients with disc herniations (n=21) or low-pressure hydrocephalus (n=10), one-third had concentrations of 2-4 nmol/L and two-thirds were below the minimum detectable concentration. The observed range for the concentration of serotonin in plasma of 14 normal subjects was 5-14 nmol/L (mean +/- SD, 9 +/- 3 nmol/L). The observed ranges for serotonin in serum were: for 10 women 520-900 (mean +/- SD: 695 +/- 110) nmol/L and for 10 men 380-680 (520 +/- 94) nmol/L.

Engbaek, F.; Voldby, B



Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis  

PubMed Central

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

Dujmovic, Irena



Application of Control Volume Analysis to Cerebrospinal Fluid Dynamics  

NASA Astrophysics Data System (ADS)

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.

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



Effect of cerebral injury on cerebrospinal fluid cyclic AMP concentration.  


Cerbrospinal fluid (CSF) cyclic adenosine-3', 5'-monophosphate (cAMP) was measured in rabbits after experimental brain injury as well as in patients with cerebral contusion and cerebral concussion. In rabbits a marked elevation lasting for two weeks was observed. From the third week onwards after the injury the CSF cAMP concentration was lower than the basal level before the injury. Dexamethasone partly inhibited the elevation. Ethanol treatment decreased the CSF cAMP values. In man, the CSF cAMP concentration was significantly higher in patients with cerebral contusion than in those with cerebral concussion. Also in the latter group the cAMP values were higher than in control patients. Due to the clear differences between the various groups, measurement of cAMP concentration in CSF might have diagnostic value in evaluation of the severity of cerebral lesion in the acute phase. Also the activities of some enzymes were measured, and the results were parallel with cAMP changes but less striking. PMID:186266

Myllyla, V V



Cerebrospinal fluid (CSF) transient responses induced by hypercapnia  

SciTech Connect

CSF transient responses to CO/sub 2/ inhalation were measured before and after facilitated perfusate flow through subarachnoid spaces of anesthetized cats during ventriculocisternal perfusion with artificial CSF containing /sup 14/C-dextran. Convective mixing of perfusate in subarachnoid spaces was augmented while infusion constant, either by impeding cisternal efflux of perfusate by raising the cisternal outflow cannula (high CSF pressure), or by preventing CSF outflow by clamping the cisternal outflow cannula (stopflow; S-F). CSF transients were also measured before and after systemic administration of phenoxybenzamine (PBZ) in order to evaluate the contribution of sympatho-adrenergic activity to craniospinal CSF redistribution and mixing. Results from high CSF pressure and S-F experiments indicate that unequilibrated CSF contributes significantly to the reduced tracer concentration in CSF volume (Vd) since SCF effluent tracer concentration (Cd) was decreased after subarachnoid facilitated flow. Further, results from S-F studies indicate that at least 50% of Cd is due to craniospinal fluid redistribution, a process which, along with CSF outflow transients, was unaffected by PBZ. Conversely, PBZ administration decreased steady state SCF formation and absorption through alpha-mediated cerebrovascular responses and/or through beta-adrenoceptor inhibition of metabolism of CSF secretory epithelium.

Fisher, M.J.



Cerebrospinal fluid flow imaging by using phase-contrast MR technique  

PubMed Central

Cerebrospinal fluid (CSF) spaces include ventricles and cerebral and spinal subarachnoid spaces. CSF motion is a combined effect of CSF production rate and superimposed cardiac pulsations. Knowledge of CSF dynamics has benefited considerably from the development of phase-contrast (PC) MRI. There are several disorders such as communicating and non-communicating hydrocephalus, Chiari malformation, syringomyelic cyst and arachnoid cyst that can change the CSF dynamics. The aims of this pictorial review are to outline the PC MRI technique, CSF physiology and cerebrospinal space anatomy, to describe a group of congenital and acquired disorders that can alter the CSF dynamics, and to assess the use of PC MRI in the assessment of various central nervous system abnormalities.

Battal, B; Kocaoglu, M; Bulakbasi, N; Husmen, G; Tuba Sanal, H; Tayfun, C



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

SciTech Connect

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.

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



Distal Aortic Perfusion and Cerebrospinal Fluid Drainage for Thoracoabdominal and Descending Thoracic Aortic Repair  

PubMed Central

Objective: To report the long-term results of our experience using cerebrospinal fluid drainage and distal aortic perfusion in descending thoracic and thoracoabdominal aortic repair. Summary Background Data: Repair of thoracoabdominal and thoracic aortic aneurysm by the traditional clamp-and-go technique results in a massive ischemic insult to several major organ systems. Ten years ago, we began to use distal aortic perfusion and cerebrospinal fluid drainage (adjunct) to reduce end-organ ischemia. Methods: Between January 1991 and February 2003, we performed 1004 thoracoabdominal or descending thoracic repairs. Adjunct was used in 741 (74%) of 1004. Multivariable data were analyzed by Cox regression. Number needed to treat was calculated as the reciprocal of the risk difference. Results: Immediate neurologic deficit was 18 (2.4%) of 741 with adjunct and 18 (6.8%) of 263 without (P < 0.0009). In high-risk extent II aneurysms, the numbers were 11 (6.6%) of 167 with adjunct, and 11 (29%) of 38 without. Long-term survival was improved with adjunct (P < 0.002). The long-term survival results persisted after adjustment for age, extent II aneurysm, and preoperative renal function. Conclusion: Use of adjunct over a long period of time has produced favorable results; approximately 1 neurologic deficit saved for every 20 uses of adjunct overall. In extent II aneurysms, where the effect is greatest, this increases to 1 saved per 5 uses. Adjunct is also associated with long-term survival, which is consistent with mitigation of ischemic end-organ injury. These long-term results indicate that cerebrospinal fluid drainage and distal aortic perfusion are safe and effective adjunct for reducing morbidity and mortality following thoracic and thoracoabdominal aortic repair.

Safi, Hazim J.; Miller, Charles C.; Huynh, Tam T.T.; Estrera, Anthony L.; Porat, Eyal E.; Winnerkvist, Anders N.; Allen, Bradley S.; Hassoun, Heitham T.; Moore, Frederick A.



Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson’s disease  

Microsoft Academic Search

Summary. Quantifications of Al, Ca, Cu, Fe, Mg, Mn, Si and Zn were performed in urine, serum, blood and cerebrospinal fluid (CSF) of 26 patients affected by Parkinson’s disease (PD) and 13 age-matched controls to ascertain the potential role of biological fluids as markers for this pathology. Analyses were performed by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field

G. Forte; B. Bocca; O. Senofonte; F. Petrucci; L. Brusa; P. Stanzione; S. Zannino; N. Violante; A. Alimonti; G. Sancesario



Cerebrospinal fluid concentrations of nitrate plus nitrite during the treatment of acute lymphoblastic leukaemia in childhood.  


To investigate the hypothesis that acute lymphoblastic leukaemia (ALL) and its treatment disturb central nervous system nitric oxide metabolism, 11 patients were studied. Serial cerebrospinal fluid (CSF) samples were collected throughout treatment and the concentration of nitrate plus nitrite (NOx) was measured. Compared to an age-matched reference population, CSF NOx was significantly increased before treatment and rose further during the induction phase of treatment. Concentrations remained high during consolidation treatment, but fell during continuing treatment and normalised by the end of treatment. In conclusion, ALL and its treatment cause an increase in central nervous system nitric oxide production. reserved. PMID:9680103

Surtees, R; Clelland, J; Heales, S



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

NASA Astrophysics Data System (ADS)

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 "synthetic 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.

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



Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury  

Microsoft Academic Search

Summary  \\u000a Objective. To determine whether sFas, caspase-3, proteins which propagate apoptosis, and bcl-2, a protein which inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in patients with severe traumatic brain\\u000a injury (TBI) and to examine the correlation of sFas, caspase-3, and bcl-2 with each other and with clinical variables.\\u000a \\u000a \\u000a Methods. sFas, caspase-3, and bcl-2 were measured in CSF of

M. Uzan; H. Erman; T. Tanriverdi; G. Z. Sanus; A. Kafadar; H. Uzun



A tomographic study of the skull base in primary spontaneous cerebrospinal fluid leaks  

Microsoft Academic Search

Introduction  This study aims to evaluate the existence of anatomic abnormalities in the skull base that could contribute to the origin\\u000a of primary spontaneous cerebrospinal fluid leaks (PSL).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twenty PSL patients were compared with 20 healthy individuals. The following features were measured through an analysis of\\u000a computed tomography scans: the angles of the petrosal bones and skull base in both the

Alexandre Varella Giannetti; Roberto Eustáquio S. Guimarães; Ana Paula M. S. Santiago; Francisco Otaviano L. Perpétuo; Marco Antônio O. Machado


Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease.  


Protozoal merozoites were identified in the cerebrospinal fluid of two sheep with neurological disease in the UK. Polymerase chain reaction (PCR) identified the merozoites as Sarcocystis capracanis, a common protozoal pathogen of goats. This is the first report of this species infecting sheep and may represent an aberrant infection with sheep acting as dead end hosts, or alternatively could indicate that sheep are able to act as intermediate hosts for S. capracanis, widening the previously reported host range of this pathogen. It is possible that S. capracanis is a previously unrecognised cause of ovine protozoal meningoencephalitis (OPM) in the UK. PMID:23312871

Formisano, P; Aldridge, B; Alony, Y; Beekhuis, L; Davies, E; Del Pozo, J; Dunn, K; English, K; Morrison, L; Sargison, N; Seguino, A; Summers, B A; Wilson, D; Milne, E; Beard, P M



Cranial computerized tomography and cerebrospinal fluid procoagulant activity in childhood acute lymphoblastic leukemia.  


Thirty-three children with acute lymphoblastic leukemia (ALL) were studied using serial cranial computerized tomography (CCT) and cerebrospinal fluid procoagulant activity (PCA) for 5 years from the time of diagnosis. PCA was also studied in control children without neurological disease and in those with a variety of neurological disorders. Temporary elevation in the CSF PCA was observed during the phase of prophylactic central nervous system treatment in ALL and there was a late rise at 2-3 years off treatment. PCA also rose in the CSF following CNS disturbance in neurologically abnormal children, which suggests that the elevation observed in ALL is not specific to myelin disturbance. PMID:3152956

O'Hare, A E; Eden, O B; Simpson, R M; Donaldson, A; Sainsbury, C P



Cerebrospinal fluid protein changes in multiple sclerosis after dental amalgam removal.  


A relationship between multiple sclerosis (MS) and dental silver-mercury fillings has been suggested by some investigators, but never proven. This study documents objective biochemical changes following the removal of these fillings along with other dental materials, utilizing a new health care model of multidisciplinary planning and treatment. The dramatic changes in photolabeling of cerebrospinal fluid (CSF) proteins following these dental interventions suggest CSF photolabeling may serve as an objective biomarker for monitoring MS. The clear-cut character of these changes should also encourage more research to better define this possible association between dental mercury and MS. PMID:9727079

Huggins, H A; Levy, T E



Predictive Value of Serum and Cerebrospinal Fluid Procalcitonin Levels for the Diagnosis of Bacterial Meningitis  

Microsoft Academic Search

Background: The value of serum and cerebrospinal fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis\\u000a was assessed and compared to other parameters which are usually used in clinical practice.\\u000a \\u000a \\u000a \\u000a \\u000a Patients: 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study.\\u000a \\u000a \\u000a \\u000a \\u000a Results: The median serum procalcitonin level in patients with

M. Jereb; I. Muzlovic; S. Hojker; F. Strle



Decreased Lithium Disposition to Cerebrospinal Fluid in Rats with Glycerol-induced Acute Renal Failure  

Microsoft Academic Search

Purpose  The lithium disposition to cerebrospinal fluid (CSF) was evaluated in rats with acute renal failure (ARF) to examine whether\\u000a electrolyte homeostasis of the CSF is perturbed by kidney dysfunction. In addition, the effects of renal failure on choroid\\u000a plexial expressions of the Na+–K+–2Cl? co-transporter (NKCC1) and Na+\\/H+ exchanger (NHE1) were also studied.\\u000a \\u000a \\u000a \\u000a Methods  After lithium was intravenously administered at a dose

Rie Sakae; Atsuko Ishikawa; Tomoko Niso; Yukiko Komori; Tetsuya Aiba; Hiromu Kawasaki; Yuji Kurosaki



Hepatic cerebrospinal fluid pseudocyst mimicking hydatid liver disease: a case report  

PubMed Central

Introduction An abdominal pseudocyst is a rare complication of a ventriculo-peritoneal shunt. Etiological factors include infection, obstruction and dislodgement. This is the first report of a hepatic cerebrospinal fluid pseudocyst mimicking hydatid liver disease. Case presentation We report the case of an 18-year-old Caucasian male patient who presented with a hepatic pseudocyst secondary to a ventriculo-peritoneal shunt, misdiagnosed as hydatid disease of the liver. Conclusion Hepatic pseudocysts, a rare complication of a ventriculo-peritoneal shunt, have similar clinical and radiological characteristics to those of hydatid liver disease. The formation of a pseudocyst should always be considered in patients with ventriculo-peritoneal shunts in situ.



Hearing loss and cerebrospinal fluid pressure: case report and review of the literature.  


A decrease in cerebrospinal fluid pressure may result in an endolymphatic hydrops through a patent cochlear aqueduct or through the fundus of the internal auditory canal. This hydrops typically leads to low-frequency sensorineural hearing loss. We describe the case of a man who presented with a subjective and objective hearing loss in addition to a headache 4 days after he had undergone a dural puncture. We treated him with a standard epidural blood patch. Immediately after treatment, his hearing improved and his headache resolved. PMID:18404909

Pogodzinski, Matthew S; Shallop, Jon K; Sprung, Juraj; Weingarten, Toby N; Wong, Gilbert Y; McDonald, Thomas J



Kearns-Sayre syndrome: cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features.  


We evaluated cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF), biogenic amines, and white matter status in six Kearns-Sayre syndrome (KSS) patients. They presented severe 5-MTHF deficiency. A significant negative correlation was observed between CSF 5-MTHF and protein concentration. CSF homovanillic acid was clearly high. Regarding neuroimaging, the main feature was hyperintensity in the basal ganglia, brainstem, and cerebral/cerebellar white matter. The severity of hemispheric white matter disturbances appeared to be qualitatively associated with 5-MTHF values. The negative correlation between 5-MTHF and proteins supports the hypothesis of impaired choroid plexus function. Interestingly, despite very low 5-MTHF, clearly high neurotransmitter metabolites were found. PMID:20388557

Serrano, Mercedes; García-Silva, María Teresa; Martin-Hernandez, Elena; O'Callaghan, Maria del Mar; Quijada, Pilar; Martinez-Aragón, Ana; Ormazábal, Aida; Blázquez, Alberto; Martín, Miguel A; Briones, Paz; López-Gallardo, Ester; Ruiz-Pesini, Eduardo; Montoya, Julio; Artuch, Rafael; Pineda, Mercedes



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


Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1-42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total tau or total tau/amyloid beta levels and the change of the Unified Parkinson Disease Rating Scale was observed. Notably, these correlations did not appear to be influenced by APOE genotype. These results are one of the very first pieces of evidence suggesting that tau and amyloid beta are critically involved in early Parkinson disease progression, potentially by a different mechanism than that in Alzheimer disease, although their applications as Parkinson disease progression markers will likely require the addition of other proteins. PMID:23644819

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



Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptoms.  


We report the concentrations of maraviroc in the cerebrospinal fluid (CSF) and plasma of six HIV-1-infected patients with both neurological impairment and detectable HIV-1 replication in CSF. One month after starting maraviroc, the viral load in the CSF decreased significantly (P = 0.005). The median (range) maraviroc concentration in plasma was 347 ng/ml (123-2678). Four patients had CSF concentrations above the protein-adjusted inhibitory concentration (IC90) of 0.57 ng/ml (0.06-10.7) with a median of 102 ng/ml (35-173). PMID:20601852

Melica, Giovanna; Canestri, Ana; Peytavin, Gilles; Lelievre, Jean D; Bouvier-Alias, Magali; Clavel, Cyril; Calvez, Vincent; Lascaux, Anne S; Katlama, Christine; Levy, Yves



The role of cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis. where are we now?  


Alzheimer's disease (AD) is a rapidly growing disease that is estimated to affect about 36 million people worldwide, therefore there is an immediate need for its' early diagnosis and treatment. A number of research studies are performed on possible accurate and reliable diagnostic biomarkers of AD. This review study provides an update on the cerebrospinal fluid (CSF) proteins that are being currently used in clinical practice and studied as biomarkers for early AD diagnosis and their future prospects, as well as relevant patents. PMID:23489287

Papaliagkas, Vasileios T



Non-linear relationships of cerebrospinal fluid biomarker levels with cognitive function: an observational study  

Microsoft Academic Search

Introduction  Levels of cerebrospinal fluid (CSF) ?-amyloid (A?) and Tau proteins change in Alzheimer's disease (AD). We tested if the relationships\\u000a of these biomarkers with cognitive impairment are linear or non-linear.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We assessed cognitive function and assayed CSF A? and Tau biomarkers in 95 non-demented volunteers and 97 AD patients. We\\u000a then tested non-linearities in their inter-relations.\\u000a \\u000a \\u000a \\u000a \\u000a Results  CSF biomarkers related to

Jonathan H Williams; Gordon K Wilcock; Jeffrey Seeburger; Aimee Dallob; Omar Laterza; William Potter; A David Smith



Linezolid for treatment of catheter-related cerebrospinal fluid infections in preterm infants.  


Ventriculostomy-related cerebrospinal fluid (CSF) infection remains a major problem in neonatal intensive care. The spectrum of pathogens causing these infections is dominated by coagulase-negative staphylococci, and vancomycin is the antibiotic of choice for treatment. However, vancomycin is known to have only poor penetration into the CSF when applied intravenously and is therefore being applied intraventricularly. The oxazolidinone linezolid has antibacterial activity against most drug-resistant Gram-positive bacteria and has been shown to have excellent penetration into the CSF in adults. Here, its successful use in five neonates with infected ventriculostomies is described. PMID:21686411

Langgartner, M; Mutenthaler, A; Haiden, N; Pollak, A; Berger, A



N-acetylaspartic acid (NAA) and N-acetylaspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid.  


N-Acetylaspartic and N-acetylaspartylglutamic acid concentrations in human ventricular, subarachnoid and lumbar cerebrospinal fluid were measured by combined gas chromatography-mass spectrometry using selected ion monitoring with deuterated internal standards. N-Acetylaspartate concentrations were in the range 55, 9, and 1 microM, respectively; N-acetylaspartylglutamate concentrations in the same fluids were in the range 8, 3 and 4 microM, respectively. There did not appear to be any difference in lumbar fluid concentrations of either compound between control subjects, schizophrenic patients, Alzheimer's disease patients and a pooled group of patients with neurological degeneration. Ventricular concentrations of both compounds were greatly increased in deceased patients suggesting that maintenance of their intracellular concentrations is probably energy dependent. The concentrations of these compounds in lumbar cerebrospinal fluid from living, and ventricular cerebrospinal fluid from deceased subjects were weakly correlated with one another. In lumbar fluid neither compound appeared to be correlated with age. Analysis of serially collected lumbar samples from two subjects showed a weak concentration gradient for both compounds. Neither antipsychotic medication nor the acid transport inhibitor probenecid had any effect on lumbar concentrations of either compound. Attempts to use anion exchange high pressure liquid chromatography with UV detection for measurement of the low concentrations of N-acetylaspartate found in cerebrospinal fluid from living subjects were unsuccessful. PMID:10492520

Faull, K F; Rafie, R; Pascoe, N; Marsh, L; Pfefferbaum, A



Optimization of PIXE analysis for Cu and other trace elements in cerebrospinal fluid to improve the detection limits  

NASA Astrophysics Data System (ADS)

An external beam PIXE system was optimized for the determination of the extremely low trace element content of normal cerebrospinal fluid. In order to improve the detection limits of the elements of interest the ultrafiltrated cerebrospinal fluid samples were deposited onto ultrathin Formvar foils and measured in a helium atmosphere. Since the main emphasis was on copper, the absorber used in the measurements was optimized to give a favourable peak/background ratio for this element. The resulting detection limits for Fe, Cu, Zn and Br were (6.3+/-2.9), (4.1+/-1.4), (8.5+/-2.6) and (18.1+/-1.1) ppb, respectively. This allowed sufficiently precise determination of the low elemental concentrations in 50 ?l of human cerebrospinal fluid.

Kupila-Rantala, T.; Hyvönen-Dabek, M.; Dabek, J. T.



14-3-3 protein detection in the cerebrospinal fluid of patients with influenza-associated encephalopathy.  


Influenza-associated encephalopathy is characterized by high fever, convulsions, and loss of consciousness associated with influenza infection in children, but its pathophysiology remains to be clarified. We examined 14-3-3 proteins, which are acidic brain proteins, in cerebrospinal fluid by immunoblotting in four patients with influenza-associated encephalopathy, four patients with influenza without encephalopathy, and four patients with another encephalopathy. Interestingly, we detected 14-3-3 proteins in all four patients with influenza-associated encephalopathy (100%) but not in any of the other patients. 14-3-3 isoforms, including beta, gamma, epsilon, xi, and theta, were found in the cerebrospinal fluid of the patients with influenza-associated encephalopathy, suggesting extensive damage to the brain. We conclude that 14-3-3 proteins in cerebrospinal fluid are highly detectable in influenza-associated encephalopathy and thus can be used as a rapid diagnostic marker. PMID:16970844

Fujii, Katsunori; Tanabe, Yuzo; Uchikawa, Hideki; Kobayashi, Kazuhiko; Kubota, Hiroaki; Takanashi, Jun-ichi; Kohno, Yoichi



Effect of atrial natriuretic factor on permeability of the blood-cerebrospinal fluid barrier.  


The demonstration of 125I-labelled atrial natriuretic factor (ANF)-binding sites on choroid plexus suggests a physiological role of ANF on the blood-cerebrospinal fluid barrier. This ultrastructural study was undertaken to determine whether ANF (0.5 microgram) alters the permeability of rat blood-cerebrospinal fluid barrier under steady states. Horseradish peroxidase (HRP) was used as a marker of protein permeability and ionic lanthanum as a marker of ionic permeability. HRP was not observed in the walls of choroid plexus vessels of control rats at 3 or 6 min, while at 12 min HRP was present in vessel walls and occasionally in continuity in the adjacent intercellular space between choroidal epithelial cells. In ANF-treated rats, HRP was observed in vessel walls and in the intercellular space between the choroidal epithelial cells up to the apical tight junctions at 3 min, indicating an accelerated passage of tracer. Although HRP was never observed beyond the apical tight junctions in control or test animals, at 6 min test rats showed ionic lanthanum within these junctions in focal areas and in continuity in the adjacent ventricular cavity. These studies demonstrate that ANF causes accelerated passage of both HRP and ionic lanthanum from blood into choroid plexuses with passage of ionic lanthanum into the ventricular cavity through the apical tight junctions of choroidal epithelial cells. The latter is in keeping with the known function of ANF in regulating water and electrolyte fluxes. PMID:1836927

Nag, S



Cerebrospinal fluid beta-glucocerebrosidase activity is reduced in Dementia with Lewy Bodies.  


The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely beta-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes - alpha-mannosidase (EC, beta-mannosidase (EC, beta-glucocerebrosidase (EC, beta-galactosidase (EC and beta-hexosaminidase (EC - in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies. PMID:19303930

Parnetti, L; Balducci, C; Pierguidi, L; De Carlo, C; Peducci, M; D'Amore, C; Padiglioni, C; Mastrocola, S; Persichetti, E; Paciotti, S; Bellomo, G; Tambasco, N; Rossi, A; Beccari, T; Calabresi, P



GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.  


Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and A??? are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10?? for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10?? and p = 3.22 × 10?? for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10?? for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10??, 0.039, 4.86 × 10??, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. PMID:23562540

Cruchaga, Carlos; Kauwe, John S K; Harari, Oscar; Jin, Sheng Chih; Cai, Yefei; Karch, Celeste M; Benitez, Bruno A; Jeng, Amanda T; Skorupa, Tara; Carrell, David; Bertelsen, Sarah; Bailey, Matthew; McKean, David; Shulman, Joshua M; De Jager, Philip L; Chibnik, Lori; Bennett, David A; Arnold, Steve E; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Williams, Julie; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Shaw, Leslie M; Trojanowski, John Q; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Peskind, Elaine R; Galasko, Douglas; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M



Psychiatric patient stratification using biosignatures based on cerebrospinal fluid protein expression clusters.  


Psychiatric disorders are caused by perturbed molecular pathways that affect brain circuitries. The identification of specific biosignatures that are the result of altered pathway activities in major depression, bipolar disorder and schizophrenia can contribute to a better understanding of disease etiology and aid in the implementation of diagnostic assays. In the present study we identified disease-specific protein biosignatures in cerebrospinal fluid of depressed (n: 36), bipolar (n: 27) and schizophrenic (n: 35) patients using the Reverse Phase Protein Microarray technology. These biosignatures were able to stratify patient groups in an objective manner according to cerebrospinal fluid protein expression patterns. Correct classification rates were over 90%. At the same time several protein sets that play a role in neuronal growth, proliferation and differentiation (NEGR1, NPDC1), neurotransmission (SEZ6) and protection from oxidative damage (GPX3) were able to distinguish diseased from healthy individuals (n: 35) indicating a molecular signature overlap for the different psychiatric phenotypes. Our study is a first step toward implementing a psychiatric patient stratification system based on molecular biosignatures. Protein signatures may eventually be of use as specific and sensitive biomarkers in clinical trials not only for patient diagnostic and subgroup stratification but also to follow treatment response. PMID:23962679

Maccarrone, Giuseppina; Ditzen, Claudia; Yassouridis, Alexander; Rewerts, Christiane; Uhr, Manfred; Uhlen, Mathias; Holsboer, Florian; Turck, Christoph W



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


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

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



Surgical Technique for the Prevention of Cerebrospinal Fluid Leakage After Bifrontal Craniotomy.  


BACKGROUND: Cerebrospinal fluid leakage and meningitis caused by frontal sinus (FS) exposure are characteristic complications of bifrontal craniotomy used for treating skull base tumors and anterior communicating artery aneurysms. Prevention of these complications is of utmost importance. We describe in detail our procedure for sealing exposed FSs during bifrontal craniotomy and present the results and outcomes of the procedure. METHODS: A total of 51 consecutive patients who had undergone bifrontal craniotomy for tuberculum sellae meningiomas, craniopharyngiomas, anterior cerebral artery aneurysms, or other frontal skull base lesions at our institute were selected for the study. Our technique for sealing exposed FSs is described below. The mucosa was sterilized using surgical cotton dipped in iodine. After craniotomy, the exposed mucosa was sealed using 7-0 nylon sutures, whereas Gelfoam with fibrin glue was used to ensure watertight closure. The exposed portions of the FSs were covered by bone covers made of internal table bone and sealed. As a final layer, frontal periosteal flaps were sutured to the frontal base dura mater. RESULTS: Postoperative cerebrospinal fluid leakage or meningitis did not occur in any of our patients. CONCLUSION: Our results indicate the effectiveness of our technique in the prevention of FS-related postoperative complications. PMID:23314023

Murai, Yasuo; Mizunari, Takayuki; Kobayashi, Shiro; Teramoto, Akira



[Determination of tetramethylpyrazine in animal serum and cerebrospinal fluid by high performance liquid chromatography].  


A reversed-phase high performance liquid chromatographic (RP-HPLC) method for the determination of the tetramethylpyrazine(TMP) in Chuanxiong extract, the animal(mouse) serum and cerebrospinal fluid has been developed. The TMP was separated on an ODS column Zorbax SB-C18(4.6 mm i.d. x 250 mm, 5 microns) at room temperature and detected by using UV detector at 270 nm. The mobile phase was methanol-water (50:50, V/V) containing 0.2 mmol/L of NH4H2PO4 flowing at a rate of 0.8 mL/min and 20 microL samples were injected. The detection limit of TMP was 1 mg/L and the calibration curve is linear between 5 and 500 mg/L with a correlation coefficient (r) of 0.999. The recovery of TMP ranged 98%-103%. The extract of Chuanxiong and pretreated serum and cerebrospinal fluid sample are stable for a week at room temperature. PMID:12541454

Ding, M Y; Luo, S Z; Liu, H; Chen, P R; Liu, D L



Reassessing cerebrospinal fluid (CSF) hydrodynamics: a literature review presenting a novel hypothesis for CSF physiology.  


The traditional model of cerebrospinal fluid (CSF) hydrodynamics is being increasingly challenged in view of recent scientific evidences. The established model presumes that CSF is primarily produced in the choroid plexuses (CP), then flows from the ventricles to the subarachnoid spaces, and is mainly reabsorbed into arachnoid villi (AV). This model is seemingly based on faulty research and misinterpretations. This literature review presents numerous evidence for a new hypothesis of CSF physiology, namely, CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit. IF and CSF are mainly formed and reabsorbed across the walls of CNS blood capillaries. CP, AV and lymphatics become minor sites for CSF hydrodynamics. The lymphatics may play a more significant role in CSF absorption when CSF-IF pressure increases. The consequences of this complete reformulation of CSF hydrodynamics may influence applications in research, publications, including osteopathic manual treatments. PMID:23768280

Chikly, Bruno; Quaghebeur, Jörgen



Stabilization media increases recovery in paucicellular cerebrospinal fluid specimens submitted for flow cytometry testing.  


BACKGROUND: Flow cytometric immunophenotpying (FCI) of cerebrospinal fluid (CSF) and other paucicellular fluids has been demonstrated to have increased sensitivity in detection of lymphoma and leukemia when compared to cytomorphology [(1) de Graaf et al., Cytometry Part B 2011, 80B:271-281; (2) Szamosi et al., CLSI Document H56-A-Body Fluid Analysis for Cellular Composition; Approved Guideline, Wayne, PA: Clinical and Laboratory Standards Institute, 2006; (3) Kraan et al., Flow Cytometric Immunophenotyping of Cerebrospinal Fluid. Current Protocols in Cytometry, Hoboken, NJ: Wiley, 2008]. However, low cellularity has been an historical problem with these samples. Several studies indicate that immediate addition of a stabilization media (e.g., RPMI with fetal calf serum (FCS)) to CSF improves the cell yield for FCI [(1) de Graaf et al.]. Such stabilization medias can, however, significantly increase cost. METHODS: We compared FCI results in CSF stabilized with RPMI 1640 (without additional additives) to results obtained using non-stabilized CSF. Samples were processed according to published CLSI guidelines [(2) Szamosi et al.]. RESULTS: About 98/105 (93%) CSF specimens stabilized with RPMI had adequate numbers of viable cells (>100) for performing FCI. About 65/217 (30%) CSF specimens without stabilization had adequate numbers of viable cells for analysis (70% either quantity not sufficient (QNS) or specimen viability below analytical limits). CONCLUSIONS: Utilizing RMPI without FCS as a stabilization media results in increased cell yield and improved FCI results. We have found FCS is not required to achieve high quality results in FCI of paucicellular CSF specimens. © 2013 International Clinical Cytometry Society. PMID:23674507

Greig, B; Stetler-Stevenson, M; Lea, J



Coordinated stasis: An overview  

Microsoft Academic Search

Coordinated stasis, as defined herein, represents an empirical pattern, common in the fossil record, wherein groups of coexisting species lineages display concurrent stability over extended intervals of geologic time separated by episodes of relatively abrupt change. In marine benthic fossil assemblages, where the pattern was first recognized, the majority of species lineages (60 to more than 80%) are present in

Carlton E. Brett; Linda C. Ivany; Kenneth M. Schopf



Association between excessive frontal cerebrospinal fluid and illness duration in males but not in females with schizophrenia  

Microsoft Academic Search

Objective. – Excessive cortical cerebrospinal fluid (CSF) has been acknowledged as a possible marker of a gray matter loss. This excess in schizophrenia is found predominantly in the prefrontal and temporal regions. We hypothesized that the poorer global outcome and treatment response in males with schizophrenia are related to a greater cortical volume loss as compared to females.Subjects and methods.

Vicente Molina; Javier Sanz; Fernando Sarramea; José M. Misiego; Carlos Benito; Tomás Palomo



ORIGINAL ARTICLE Cerebrospinal fluid and serum zinc, copper, magnesium and calcium levels in children with Idiopathic seizure  

Microsoft Academic Search

Objectives: The present study was conducted to observe the alteration and their relations in cerebrospinal fluid (CSF) and serum Zinc (Zn), Copper (Cu), Magnesium (Mg) and calcium (Ca) levels in patients with different types of idiopathic seizure and to determine the ratios of serum and CSF Ca\\/Mg and Cu\\/Zn. Methods: The children aged 1 to 14 years, having two or




Brain Metabolic Correlates of Cerebrospinal Fluid Beta-Amyloid 42 and Tau in Alzheimer’s Disease  

Microsoft Academic Search

Background: The cerebrospinal fluid (CSF) proteins ?-amyloid 42 (A?42) and Tau are believed to indirectly reflect some core pathological features of Alzheimer’s disease (AD). Their topographic origin and their association with synaptic dysfunction are still not well understood. Aim: The present study aimed to explore possible associations between cerebral glucose metabolism and CSF A?42 as well as Tau protein levels

Ruth Vukovich; Robert Perneczky; Alexander Drzezga; Hans Förstl; Alexander Kurz; Matthias Riemenschneider



Cerebrospinal fluid drainage and distal aortic perfusion: Reducing neurologic complications in repair of thoracoabdominal aortic aneurysm types I and II  

Microsoft Academic Search

Purpose: This study was conducted to evaluate the role of cerebrospinal fluid (CSF) drainage and distal aortic perfusion (DAP) in the prevention of postoperative neurologic complications for high-risk patients who had undergone type I and type II thoracoabdominal aortic aneurysm (TAAA) repair.Methods: CSF drainage and DAP were used as an adjunct in the treatment of 94 patients with TAAA (31

Hazim J. Safi; Kenneth R. Hess; Mark Randel; Dimitrios C. Iliopoulos; John C. Baldwin; Ravi K. Mootha; Salwa S. Shenaq; Roy Sheinbaum; Thomas Greene



Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression  

Microsoft Academic Search

In contrast to relapse, the mechanisms of multiple sclerosis (MS) disease progression are less understood and appear not to be exclusively inflammatory in nature. In this pilot study we investigated the relationship between disturbed CNS energy metabolism and MS disease progression. We tested the hypothesis that cerebrospinal fluid (CSF) concentrations of sorbitol, fructose, and lactate, all metabolites of extra-mitochondrial glucose

William T. Regenold; Pornima Phatak; Michael J. Makley; Roger D. Stone; Mitchel A. Kling



Detection of Aspergillus DNA in Cerebrospinal Fluid from Patients with Cerebral Aspergillosis by a Nested PCR Assay  

Microsoft Academic Search

Invasive aspergillosis (IA), a complication with high mortality rates, especially in disseminated IA with cerebral involvement, is difficult to diagnose. Biopsy of cerebral lesions is often not feasible, and culture of Aspergillus spp. from cerebrospinal fluid (CSF) is frequently negative. New molecular methods have emerged for diagnosing IA. So far, there are only few reports of Aspergillus DNA detection in

M. Hummel; B. Spiess; K. Kentouche; S. Niggemann; C. Bohm; S. Reuter; M. Kiehl; H. Morz; R. Hehlmann; D. Buchheidt



Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans  

Microsoft Academic Search

Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinal fluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure

Kathleen T Sachse; Edwin K Jackson; Stephen R Wisniewski; Delbert G Gillespie; Ava M Puccio; Robert S B Clark; C Edward Dixon; Patrick M Kochanek



Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture  

Microsoft Academic Search

We report a patient treated for small lymphocytic lymphoma\\/leukemia with cerebral venous and sinus thrombosis (CVST) after lumbar puncture with intrathecal administration of methotrexate (MTX). He also developed a cerebrospinal fluid flow block. This is the first report of an association between lumbar puncture and intrathecally administered MTX and the development of CVST. Intrathecal treatment in this patient was discontinued

H. P. Bienfait; J. Gijtenbeek; M. van den Bent; H. de Bruin; P. Voogt; M. Pillay



Rapid determination of piracetam in human plasma and cerebrospinal fluid by micellar electrokinetic chromatography with sample direct injection  

Microsoft Academic Search

A simple micellar electrokinetic chromatography (MEKC) method with UV detection at 200nm for analysis of piracetam in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of piracetam from biological matrix was performed at 25°C using a background electrolyte consisting of Tris buffer with sodium dodecyl sulfate (SDS) as the electrolyte solution.

Hsin-Hua Yeh; Yuan-Han Yang; Ju-Yun Ko; Su-Hwei Chen



Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia  

Microsoft Academic Search

Background: The role of various proteases in the pathogenesis of Alzheimer's disease is well documented. Recently, many members of the human tissue kallikrein family, a group of 15 secreted serine proteases, were found to be highly expressed in the central nervous system (CNS). Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies.Methods: We quantified

Eleftherios P Diamandis; Andreas Scorilas; Tadaaki Kishi; Kaj Blennow; Liu-Ying Luo; Antoninus Soosaipillai; Alfred W Rademaker; Magnus Sjogren



Fear and power-dominance motivation: proposed contributions of peptide hormones present in cerebrospinal fluid and plasma  

Microsoft Academic Search

We propose that fear and power-dominance drive motivation are generated by the presence of elevated plasma and cerebrospinal fluid (CSF) levels of certain peptide hormones. For the fear drive, the controlling hormone is corticotropin releasing factor, and we argue that elevated CSF and plasma levels of this peptide which occur as a result of fear-evoking and other stressful experiences in

Terence V. Sewards; Mark A. Sewards



Identification of nociceptin in human cerebrospinal fluid: comparison of levels in pain and non-pain states  

Microsoft Academic Search

We have measured plasma and cerebrospinal fluid (CSF) concentrations of nociceptin, the endogenous agonist of the orphan opioid receptor-like receptor (ORL- 1). We studied two groups of ten patients presenting for elective Caesarean section (Group E) or in established labour and requiring combined spinal epidural anaesthesia for pain relief (Group L). Nociceptin was identified in all CSF samples with mean±SD

H Brooks; C. D Elton; D Smart; D. J Rowbotham; A. T McKnight; D. G Lambert



Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease  

Microsoft Academic Search

Background: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase and may alter NO production during pathological conditions. Concerning Alzheimer’s disease (AD), there are reports on altered cerebral NO metabolism, but only few studies on ADMA concentrations in plasma and cerebrospinal fluid (CSF). Methods: We assessed plasma ADMA in 80 AD patients and 80 age- and gender-matched

Sönke Arlt; Friedrich Schulze; Martin Eichenlaub; Renke Maas; Jan T. Lehmbeck; Edzard Schwedhelm; Holger Jahn; Rainer H. Böger



Decrease of E and EA but Not EAC Rosette Formation after Incubation of Blood Lymphocytes in Cerebrospinal Fluid  

Microsoft Academic Search

Peripheral blood lymphocytes (PBL) were incubated in autologous cerebrospinal fluid (CSF) or Hanks’ balanced salt solution (HBSS) for between 5 and 60 min at 37 °C. Incubation in CSF caused an increase in cell death as measured by trypan blue inclusion. Incubation in CSF also resulted in a decreased percentage of E and EA rosette-forming cells (RFC) – but not

A. Næss



Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System  

Microsoft Academic Search

The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of

Amanda McRae-Degueurce; Serney Booj; Kenneth Haglid; Lars Rosengren; Jan Erik Karlsson; Ingvar Karlsson; Anders Wallin; Lars Svennerholm; Carl-Gerhard Gottfries; Annica Dahlstrom



Cerebrospinal Fluid Leptin in Anorexia Nervosa: Correlation with Nutritional Status and Potential Role in Resistance to Weight Gain  

Microsoft Academic Search

Studies in rodents have shown that leptin acts in the central ner- vous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects in- cluded 11 female patients with anorexia nervosa studied




Excitability of neurons in the ventromedial nucleus in rat hypothalamic slices: modulation by amino acids at cerebrospinal fluid levels  

Microsoft Academic Search

Free amino acid composition of cerebrospinal fluid (CSF) in the rat was measured to examine if electrical activity of neurons in the ventromedial nucleus of the hypothalamus (VMH) is modulated by amino acids at CSF levels. In CSF collected through a cannula in the cerebromedullary cistern of freely moving rats, the total concentration of amino acids was 979 ?M, while

Fusae Nishimura; Masugi Nishihara; Masato Mori; Kunio Torii; Michio Takahashi



Detection of Measles Virus Genomic RNA in Cerebrospinal Fluid of Children with Regressive Autism: a Report of Three Cases  

Microsoft Academic Search

In light of encephalopathy presenting as autistic regression (autistic encephalopathy, AE) closely following measles-mumps- rubella (MMR) vaccination, three children underwent cerebrospinal fluid (CSF) assessments including studies for measles virus (MV). All three children had concomitant onset of gastrointestinal (GI) symptoms and had already had MV genomic RNA detected in biopsies of ileal lymphoid nodular hyperplasia (LNH). Presence of MV Fusion

J. J. Bradstreet; J. El Dahr; A. Anthony; J. J. Kartzinel; A. J. Wakefield



Disturbances of the clotting and anticlotting system of the blood and cerebrospinal fluid in experimental brain trauma  

Microsoft Academic Search

In the course of an experimental study of the effect of brain trauma on the structure of the vascular system of the choroid plexuses,the writer noted that, besides a disturbance of the coagulability of the blood, components of the clotting and anticlotting systems appear in the cerebrospinal fluid (CSF). After brain trauma, thechemieal composition of the CSF is known to

Vo P. Yurchenko



Transforming growth factor-?1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease  

Microsoft Academic Search

Transforming growth factor (TGF)-?1 content was measured for the first time in the brain (caudate nucleus, putamen, and cerebral cortex) and in ventricular cerebrospinal fluid (VCSF) from control and parkinsonian patients by a sandwich enzyme immunoassay. The concentrations of TGF-?1 were significantly higher in the dopaminergic striatal regions in parkinsonian patients than those in controls, but were not significantly different

Makio Mogi; Minoru Harada; Tomoyoshi Kondo; Hirotaro Narabayashi; Peter Riederer; Toshiharu Nagatsu



Cerebrospinal fluid of Alzheimer's disease and dementia with Lewy bodies patients enhances ?-synuclein fibril formation in vitro  

Microsoft Academic Search

Deposition of ?-synuclein (?S) aggregates inside brain cells is a pathological hallmark of several neurodegenerative diseases, including Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Recently, extracellular ?S was detected in cerebrospinal fluid (CSF) and plasma of humans. We investigated whether CSF influences ?S aggregation in vitro using fluorescence spectroscopy with thioflavin S and electron microscopy. We found that

Kenjiro Ono; Moeko Noguchi-Shinohara; Mitsuhiro Yoshita; Hironobu Naiki; Masahito Yamada



Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species  

Microsoft Academic Search

BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to

Miles Johnston; Andrei Zakharov; Christina Papaiconomou; Giselle Salmasi; Dianna Armstrong



A flexible metal ventricular catheter for treatment of complicated and protracted infections of the cerebrospinal fluid spaces: Preliminary experiences  

Microsoft Academic Search

Summary In the management of shunt infection, the use of ventricular catheters made of silicone rubber for the temporary external drainage of cerebrospinal fluid (CSF) is general practice. However, the eradication of the primary source of infection may be hindered by the affinity of bacteria to silicone-based material. Compared to silicone catheters, a metal drainage device for temporary ventriculostomy appears

U. Vieweg; B. Kaden; D. Van Roost



Cerebrospinal Fluid (1,3)-?-d-Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis  

PubMed Central

This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-?-d-glucan in cerebrospinal fluid during the current U.S. outbreak of fungal meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.

Lyons, Jennifer L.; Roos, Karen L.; Marr, Kieren A.; Neumann, Henry; Trivedi, Julie B.; Kimbrough, Dorlan J.; Steiner, Lisa; Thakur, Kiran T.; Harrison, Daniel M.



Improved resolution of human cerebrospinal fluid proteins on two-dimensional gels.  


Proteomics combines two-dimensional gel electrophoresis and peptide mass fingerprinting and can potentially identify a protein(s) unique to disease. Such proteins can be used either for diagnosis or may be relevant to the pathogenesis of disease. Because patients with multiple sclerosis (MS) have increased amounts of immunoglobulin (Ig) G in their cerebrospinal fluid (CSF) that is directed against an as yet unidentified protein, we are applying proteomics to MS CSF, studies that require optimal separation of proteins in human CSF. We found that recovery of proteins from CSF of MS patients was improved using ultrafiltration, rather than dialysis, for desalting. Resolution of these proteins was enhanced by acetone precipitation of desalted CSF before electrophoresis and by fractionation of CSF using Cibacron Blue sepharose affinity chromatography. Improved protein recovery and resolution will facilitate excision from gels for analysis by peptide mass fingerprinting. PMID:14582772

Hammack, B N; Owens, G P; Burgoon, M P; Gilden, D H



Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms.  


Anandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated ?(9)-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use. PMID:23580381

Morgan, Celia J A; Page, Emma; Schaefer, Carola; Chatten, Katharine; Manocha, Amod; Gulati, Sumit; Curran, H Valerie; Brandner, Brigitta; Leweke, F Markus



Effects of spatial variation of skull and cerebrospinal fluid layers on optical mapping of brain activities  

NASA Astrophysics Data System (ADS)

In order to investigate the effects of anatomical variation in human heads on the optical mapping of brain activity, we perform simulations of optical mapping by solving the photon diffusion equation for layered-models simulating human heads using the finite element method (FEM). Particularly, the effects of the spatial variations in the thicknesses of the skull and cerebrospinal fluid (CSF) layers on mapping images are investigated. Mapping images of single active regions in the gray matter layer are affected by the spatial variations in the skull and CSF layer thicknesses, although the effects are smaller than those of the positions of the active region relative to the data points. The increase in the skull thickness decreases the sensitivity of the images to active regions, while the increase in the CSF layer thickness increases the sensitivity in general. The images of multiple active regions are also influenced by their positions relative to the data points and by their depths from the skin surface.

Wang, Shuping; Shibahara, Nanae; Kuramashi, Daishi; Okawa, Shinpei; Kakuta, Naoto; Okada, Eiji; Maki, Atsushi; Yamada, Yukio



Elevated glial fibrillary acidic protein levels in the cerebrospinal fluid of patients with narcolepsy.  


Glial fibrillary acidic protein (GFAP) is an established indicator of astrogliosis. Therefore, variable cerebrospinal fluid (CSF) concentrations of this protein might reflect disease-specific pathologic profiles. In patients with narcolepsy, a loss of hypocretin-1 (hcrt-1) neurons in the brain and low concentrations of hcrt-1 in CSF have been reported. We performed a commercially available enzyme-linked immunosorbent assay to investigate if GFAP also is altered in the CSF of these patients. Here we detected significantly higher CSF levels of GFAP in patients with low hcrt-1 levels, of which the majority had a diagnosis of narcolepsy and cataplexy (NC); however, this finding was not observed in patients with hcrt-1 levels that were within reference range. In conclusion, GFAP may be useful as an additional disease biomarker in patients with narcolepsy, and this hypothesis should be investigated in larger studies. PMID:23746601

Feneberg, Emily; Steinacker, Petra; Lehnert, Stefan; Böhm, Bernhard; Mayer, Geert; Otto, Markus



Plasma Cell Cerebrospinal Fluid Pleocytosis Does Not Predict West Nile Virus Infection  

PubMed Central

Purpose. Diagnosis of WNV (WNV) relies upon serologic testing which may take several days after the onset of clinical symptoms to turn positive. Anecdotal reports suggest the presence of plasma cells or plasmacytoid lymphocytes in the cerebrospinal fluid (CSF) may be an early indicator of WNV infection. Methods. The CSFs of 89 patients (12 with WNV, 12 with other viral illness {OVI}, and 65 with nonviral illness{NVI}) were compared for the presence of either plasma cells or plasmacytoid lymphocytes. Results. Plasma cells were rarely seen in any of the patients. Plasmacytoid lymphocytes were more commonly seen in WNV (58%) and OVI (50%) than NVI (11%). The differences were significant for WNV versus NVI, but not WNV versus OVI (P < 0.001 and P = 0.58, resp.). Conclusions. A CSF pleocytosis with plasma cells or plasmacytoid lymphocytes was neither sensitive nor specific for the diagnosis of WNV infection.

Jordan, Michael; Nagpal, Avish; Newman, William; Thompson, Paul A.; Carson, Paul J.



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

PubMed Central

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

Palha, Joana A.; Santos, Nadine C.; Marques, Fernanda; Sousa, Joao; Bessa, Joao; Miguelote, Rui; Sousa, Nuno; Belmonte-de-Abreu, Paulo



Postoperative cerebrospinal fluid leak after septoplasty: A potential complication of occult anterior skull base encephalocele  

PubMed Central

Postoperative cerebrospinal fluid (CSF) rhinorrhea after septoplasty is a known entity resulting from errors in surgical technique and improper handling of the perpendicular plate of the ethmoid bone. When these occur, urgent management is necessary to prevent deleterious sequelae such as meningitis, intracranial abscess, and pneumocephalus. Encephaloceles are rare occurrences characterized by herniation of intracranial contents through a skull base defect that can predispose patients to CSF rhinorrhea. In this report, we present a case of CSF rhinorrhea occurring 2 weeks after septoplasty likely from manipulation of an occult anterior skull base encephalocele. To our knowledge, no previous similar case has been reported in the literature. Otolaryngologists should be aware of the possibility of occult encephaloceles while performing septoplasties because minimal manipulation of these entities may potentially result in postoperative CSF leakage.

Soni, Resha S.; Choudhry, Osamah J.; Liu, James K.



Jacalin-unbound fraction of Taenia saginata in immunodiagnosis of neurocysticercosis in human cerebrospinal fluid.  


The aim of this study was to evaluate jacalin-bound fraction (JBF) and jacalin-unbound fraction (JUF) of the total saline extract from Taenia saginata metacestodes for human neurocysticercosis (NC) immunodiagnosis in cerebrospinal fluid. Total extract, JBF, and JUF were separated by affinity chromatography using Sepharose(®)-jacalin and were tested in enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) to detect immunoglobulin G. In ELISA test, JUF showed the higher diagnostic efficiency and specificity indexes, 92% and 100%, respectively. In WB, 5 immunodominant proteins (39-42, 47-52, 64-68, 70, and 75 kDa) were detected when using JUF. In conclusion, the results achieved demonstrate that JUF, obtained from T. saginata metacestodes, are an important source of specific peptides and are efficient in the diagnosis of NC. PMID:20846809

da Silva Nunes, Daniela; da Silva Ribeiro, Vanessa; Manhani, Marianna Nascimento; Costa-Cruz, Julia Maria



Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.  


Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS. PMID:23225075

Roos, Per M; Vesterberg, Olof; Syversen, Tore; Flaten, Trond Peder; Nordberg, Monica



Interpretation of positive molecular tests of common viruses in the cerebrospinal fluid.  


Many central nervous system infections are historically difficult to diagnose. Polymerase chain reaction (PCR) has revolutionized the diagnosis of these infections because of their high sensitivity despite the lack of data on clinical usefulness. We conducted a retrospective study that included patients with positive cerebrospinal fluid (CSF) PCR for herpes simplex virus, varicella-zoster virus, JC virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) between January 2009 and December 2011. The positive results were grouped into definite, likely, and possible true positives and likely false-positive categories based on pre-specified definitions specific to each virus. Of 1663 CSF viral PCR tests, 88 were positive (5%). The combined positive predictive value (PPV) was 58%. The PPVs were least for CMV and EBV at 29 and 37%, respectively. A positive CSF viral PCR result has to be interpreted with caution due to several false-positive results. PMID:24035384

Bhaskaran, Archana; Racsa, Lori; Gander, Rita; Southern, Paul; Cavuoti, Dominick; Alatoom, Adnan



A Window into the Heterogeneity of Human Cerebrospinal Fluid A? Peptides  

PubMed Central

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

Ghidoni, Roberta; Paterlini, Anna; Albertini, Valentina; Stoppani, Elena; Binetti, Giuliano; Fuxe, Kjell; Benussi, Luisa; Agnati, Luigi F.



Scanning electron microscopic observations of the arachnoid granulations in monkeys with cerebrospinal fluid hypotension.  


The changes in arachnoid granulations following the depletion of cerebrospinal fluid (CSF) were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In the normal tissue, the arachnoid granulations located at the inner walls of the superior sagittal sinus and the straight sinus had bulging protrusions of various sizes, as viewed with the SEM. With TEM, the outermost cells covering the surface of the arachnoid granulations had "giant vacuoles" in the cytoplasm. With CSF hypotension, the arachnoid granulations were smaller in size and the outermost layer of cells were thinner. The vacuoles in the outer layer were not developed. In the apical region of the individual arachnoid granulations with CSF hypotension, the arachnoid cells were densely clustered under the endothelial cells. With recovery to normal CSF pressure, the arachnoid cells appeared to protrude between the endothelial cells covering the apical portion of the arachnoid granulation. PMID:8007628

Takahashi, Y; Shigemori, M; Inokuchi, T; Miyajima, S; Maehara, T; Wakimoto, M; Matsuo, H



Effects of aluminum chloride on the rate of secretion of the cerebrospinal fluid  

SciTech Connect

The claim that AlCl/sub 3/ could produce 100% inhibition of cerebrospinal fluid secretion was investigated using ventriculocisternal perfusion in the rabbit, and it was shown that a large part of this inhibition was an artefact due to a pH sensitivity of Blue Dextran, used as an indiffusible marker, caused by AlCl/sub 3/. Thus the true inhibition found, using (/sup 3/H)labeled markers, was about 33% and usually only partly reversible. Penetration of /sup 22/Na from blood into the perfused ventricles was partially inhibited by AlCl/sub 3/. The effects of some other acid buffer systems, namely acetate and phosphate, on rate of secretion were measured; the results were highly variable. When mean arterial pressure was measured, it was found to be unaffected by AlCl/sub 3/ but elevated with acetate and phosphate buffer mixtures.

Zlokovic, B.V.; Davson, H.; Preston, J.E.; Segal, M.B.



Cerebrospinal fluid immunoreactive substance P and somatostatin in neurological patients with peripheral and spinal cord disease.  


We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance. PMID:2468107

Cramer, H; Rösler, N; Rissler, K; Gagnieu, M C; Renaud, B



Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.  

PubMed Central

Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis.

Lee, J B; Farshy, C E; Hunter, E F; Hambie, E A; Wobig, G H; Larsen, S A



Two dimensional difference gel electrophoresis analysis of cerebrospinal fluid in tuberculous meningitis patients.  


Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. Present methods to diagnose TBM are not suitable for early diagnosis. Molecular markers and sensitive methods to identify them in the early stage of infection of TBM are critically needed for efficient management. We have done the proteomic analysis of TBM cerebrospinal fluid (n=20) with 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. We identified 11 human proteins and 8 mycobacterial proteins with changed expression levels in comparison to controls. Arachidonate 5-lipoxygenase and glial fibrillary acidic protein, two of the identified proteins, were validated with western blot technique on a larger set of disease and control samples (n=40). These two proteins were also analyzed in fungal meningitis samples. We suggest that arachidonate 5-lipoxygenase can be considered for validation as a potential marker for diagnosis of TBM. PMID:21723968

Kataria, Jitender; Rukmangadachar, Lokesh A; Hariprasad, Gururao; O, Jithesh; Tripathi, Manjari; Srinivasan, Alagiri



Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation  

SciTech Connect

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

Meyer, J.S.; Tachibana, H.; Hardenberg, J.P.; Dowell, R.E. Jr.; Kitagawa, Y.; Mortel, K.F.



Plasma oxytocin and vasopressin do not predict neuropeptide concentrations in human cerebrospinal fluid.  


The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinal fluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification. PMID:23574490

Kagerbauer, S M; Martin, J; Schuster, T; Blobner, M; Kochs, E F; Landgraf, R



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

PubMed Central

Darunavir/ritonavir monotherapy maintains HIV suppression in most patients who have achieved an undetectable viral load on combination antiretroviral treatment, and is increasingly used in the clinic. However, concerns have been raised about the effectiveness of ritonavir-boosted protease inhibitor (PI/r) monotherapy in the prevention of HIV replication in the central nervous system (CNS). Here we report the cases of 2 patients on darunavir/r maintenance monotherapy with cerebrospinal fluid viral breakthrough together with increased immunoactivation and biomarker signs of neuronal injury. These 2 cases raise concerns about the effectiveness of darunavir/ritonavir monotherapy in HIV CNS infection. Thus, we recommend caution with protease inhibitor monotherapy until CNS results have been obtained from clinical studies.



Antibodies to varicella zoster virus in the cerebrospinal fluid of neonates with seizures  

PubMed Central

Four neonates with convulsions had IgG antibodies in their cerebrospinal fluid (CSF) to varicella zoster virus (VZV). These antibodies were found in the sera of two of these patients after the age of 6 months. Antibodies to 16 different microbes were studied from the serum and CSF of 201 neonates with neurological problems. The presence of DNA specific to HSV-1, HSV-2, and VZV in the CSF was also investigated using the polymerase chain reaction (PCR). Antibodies to VZV were detected in the CSF of four neonates. Antibody indices suggested production of VZV specific antibodies in the central nervous system. These findings suggest that intrathecal production of antibodies to VZV can appear in neonates with neurological problems, which suggests that intrauterine VZV infection can be acquired without cutaneous symptoms in the mother.??

Mustonen, K.; Mustakangas, P.; Smeds, M.; Mannonen, L.; Uotila, L.; Vaheri, A.; Koskiniemi, M.



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


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. PMID:21559420

Lubieniecka, Joanna M; Streijger, Femke; Lee, Jae H T; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K; Coorssen, Jens R; Foster, Leonard J; Grigliatti, Thomas A; Tetzlaff, Wolfram



Biomarkers for Severity of Spinal Cord Injury in the Cerebrospinal Fluid of Rats  

PubMed Central

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.

Lubieniecka, Joanna M.; Streijger, Femke; Lee, Jae H. T.; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K.; Coorssen, Jens R.; Foster, Leonard J.; Grigliatti, Thomas A.; Tetzlaff, Wolfram



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

SciTech Connect

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.

Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J. (Laboratoire d'etude du Metabolisme Azote, Ceyrat (France))



Oxidative stress in cerebrospinal fluid of patients with aseptic and bacterial meningitis.  


This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS) and antioxidant defense systems such as superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and ascorbic acid. TBARS levels, SOD and GST activity increase in aseptic meningitis and in bacterial meningitis. The ascorbic acid concentration increased significantly in patients with both meningitis types. The reduced glutathione levels were reduced in CSF of patients with aseptic and bacterial meningitis. In present study we may conclude that oxidative stress contributes at least in part to the severe neurological dysfunction found in meningitis. PMID:19205881

de Menezes, Charlene Cavalheiro; Dorneles, Aracélli Gnatta; Sperotto, Rita Leal; Duarte, Marta Medeiros Frescura; Schetinger, Maria Rosa Chitolina; Loro, Vania Lúcia



Low levels of LTB4 in cerebrospinal fluid of AIDS patients with cryptococcal meningitis.  


In this study we evaluated the release of leukotriene B4 (LTB4) in the cerebrospinal fluid (CSF) of 12 patients with Acquired Immunodeficiency Syndrome (AIDS), which disease was complicated by Cryptococcal Meninigitis and in CSF of 12 control subjects with inflammatory and degenerative pathologies of the Central Nervous System (CNS). We obtained low levels of LTB4 in all the AIDS patients (mean 60.5 pg/ml), while the HIV negative subjects with degenerative and inflammatory pathologies of CNS showed a mean of 91.5 pg/ml. The finding of low levels of this inflammatory reaction mediator agrees with the limited clinical symptoms of cryptococcal meningoencephalitis in patients affected by AIDS. PMID:8735435

Froldi, M; Parma, M; Marenzi, R; Piona, A; Lorini, M; Nobile Orazio, E; Castagna, A; Lazzarin, A



Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections  

PubMed Central

ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.



Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma, seminal plasma, and cerebrospinal fluid.  


Efavirenz (EFV) is one of the most commonly prescribed antiretrovirals for use in the treatment of human immunodeficiency virus (HIV) infection. EFV is extensively metabolized by cytochrome P450 to a number of oxygenated products; however, the pharmacologic activity and distribution of these metabolites in anatomic compartments have yet to be explored. The systemic distribution of EFV oxidative metabolites was examined in blood plasma, seminal plasma, and cerebrospinal fluid from subjects on an EFV-based regimen. The 8-hydroxy EFV metabolite was detected in blood plasma, seminal plasma, and cerebrospinal fluid, with median concentrations of 314.5 ng/ml, 358.5 ng/ml, and 3.37 ng/ml, respectively. In contrast, 7-hydroxy and 8,14-hydroxy EFV were only detected in blood plasma and seminal plasma with median concentrations of 8.84 ng/ml and 10.23 ng/ml, and 5.63 ng/ml and 5.43 ng/ml, respectively. Interestingly, protein-free concentrations of metabolites were only detectable in seminal plasma, where a novel dihdyroxylated metabolite of EFV was also detected. This accumulation of protein-free EFV metabolites was demonstrated to be the result of differential protein binding in seminal plasma compared with that of blood plasma. In addition, the oxidative metabolites of EFV did not present with any significant pharmacologic activity toward HIV-1 as measured using an HIV green fluorescent protein single-round infectivity assay. This study is the first to report the physiologic distribution of metabolites of an antiretroviral into biologic compartments that the virus is known to distribute and to examine their anti-HIV activity. These data suggest that the male genital tract may be a novel compartment that should be considered in the evaluation of drug metabolite exposure. PMID:23166317

Avery, Lindsay B; VanAusdall, Jennifer L; Hendrix, Craig W; Bumpus, Namandjé N



Aminoterminally truncated and oxidized amyloid-? peptides in the cerebrospinal fluid of Alzheimer's disease patients.  


Carboxyterminally elongated and aminoterminally truncated amyloid-? (A?) peptides and their oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to clarify the diagnostic impact of the A? peptides 1-38ox, 2-40, and 2-42 peptides on the neurochemical cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD). For this purpose, 22 patients with AD and 20 non-demented disease controls (NDC) were comparatively analyzed for their cerebrospinal fluid pattern of A?1-38ox, A?2-40, and A?2-42 along with A?1-37, A?1-38, A?1-39, A?1-40, A?1-40ox, and A?1-42 using a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and subsequent analysis in the A?-SDS-PAGE/immunoblot. The A? peptides 1-38ox, 2-40, and 2-42 could not be consistently detected in the investigated CSF samples, which applied to samples from AD and NDC patients alike. Otherwise, our approach revealed a striking decrease of A?1-42 and A?2-42, but not of A?1-38ox and A?2-40 in AD. Both A?1-42 and A?2-42 reached reasonable accuracies for diagnosing AD alone as well as in relation to A?1-40, A?1-38, or the sum of all measured A? peptides. A?1-38ox was negatively correlated to the Mini-Mental Status Examination score of AD patients, indicating that this peptide to linked to disease severity. We conclude that an exact analysis of CSF A? peptides regarding their carboxy- and aminoterminus as well as posttranslational modification may be a promising approach for diagnosing and tracking AD. PMID:22460324

Bibl, Mirko; Gallus, Marion; Welge, Volker; Esselmann, Hermann; Wiltfang, Jens



Serum and Cerebrospinal Fluid Levels of Transthyretin in Lewy Body Disorders with and without Dementia  

PubMed Central

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 Abeta1–42, 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.

Gauger, Tina; Odoj, Bartholomaus; Schmid, Benjamin; Schulte, Claudia; Deuschle, Christian; Heck, Susanna; Apel, Anja; Melms, Arthur; Gasser, Thomas; Berg, Daniela



On the significance of monoamines and their metabolites in the cerebrospinal fluid of the sheep.  

PubMed Central

Assays capable of concurrently measuring small quantities of noradrenaline, dopamine, serotonin, and several of their metabolites in cerebrospinal fluid (c.s.f.) were developed by the use of high performance liquid chromatography with electrochemical detection. For comparison, cortical subarachnoid, ventricular, cisternal and lumbar c.s.f. were obtained by puncture under barbiturate anaesthesia in sheep. Basal concentrations related to the adrenergic system, including methoxyhydroxyphenylglycol (MHPG), were similar in ventricular, cisternal and lumbar c.s.f., and those of the serotoninergic metabolites, 5-hydroxyindole-3-acetylacetic acid (5-HIAA), were similar in ventricular and cisternal c.s.f. High concentrations of the dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found only in ventricular c.s.f. Monoamine metabolites in ventricular c.s.f. under basal conditions and after various experimental manipulations were then determined over periods of 3 months in two different breeds of sheep fitted chronically with cannulae in lateral ventricles. A dose-related accumulation of all the acidic monoamine metabolites was recorded during treatment with probenecid. The increase in 5-HIAA was linear after administration of increased doses of tryptophan and 5-hydroxytryptophan. The concentrations of dopamine, DOPAC and HVA in the ventricular c.s.f. reflected the response of the dopaminergic system to agents capable of crossing the blood-brain barrier. It is concluded that cerebral metabolism in conscious sheep could be indirectly approached by recording the concentration of end-products of dopamine metabolism in ventricular cerebrospinal fluid, obtained under conditions of minimal stress.

Ruckebusch, M; Sutra, J F



Attenuated antiaggregation effects of magnetite nanoparticles in cerebrospinal fluid of people with Alzheimer's disease.  


It is well known that oligomeric/aggregated amyloid ? peptides are a key player in the pathogenesis of Alzheimer's disease and that different nanoparticles influence oligomerization/aggregation processes in experiments in vitro. Our previous results demonstrated antiaggregation effects of magnetite nanoparticles in the case of protein lysozyme, however, they have yet to be supported by biological samples containing peptides/proteins preaggregated in vivo. In the study, Thioflavin T based fluorescence was evaluated on cerebrospinal fluid samples from people with Alzheimer's disease/multiple sclerosis and corresponding age-related controls using magnetite nanoparticles incubated for 24 h. Our results are as follows: (i) fluorescence of samples without nanoparticles was significantly higher in both older groups (old controls and people with Alzheimer's disease) than in those of younger (young controls and people with multiple sclerosis), (ii) nanoparticles did not markedly influence a fluorescence intensity in young people but eliminated it in both old groups; nevertheless, the effects of nanoparticles were significantly lower in patients with Alzheimer's disease then in the age-matched controls, and finally (iii) significant positive correlation was observed between fluorescence of samples without nanoparticles and levels of phospho-tau. Our results support studies reporting enhanced aggregation of different peptides/proteins occurring during normal aging and demonstrate for the first time that peptides/proteins preaggregated in vivo during Alzheimer's disease are more resistant to the antiaggregation effects of magnetite nanoparticles than those of age-matched controls. A significant correlation with phospho-tau levels indicate that the in vitro test with magnetite nanoparticles and Thioflavin T dye on cerebrospinal fluid could be sensitive to changes mediated by early Alzheimer's disease stages. PMID:20721410

Gažová, Zuzana; Antošová, Andrea; Krištofiková, Zdena; Bartoš, Aleš; Rí?ný, Jan; Cechová, Linda; Klaschka, Jan; Rípová, Daniela



Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological disease  

PubMed Central

Objectives: To measure cerebrospinal fluid (CSF) tau in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. Methods: CSF tau was prospectively measured in 76 consecutive HIV infected patients admitted to a specialist unit at UCL Hospitals, London, for investigation of acute neurological episodes: the results were compared with the clinical diagnoses. Results: 24 patients had HIV associated dementia complex (HADC), 10 had lymphoma (including four with primary CNS lymphoma), 20 had cerebral infections (including five with CMV encephalitis, five with VZV infection, seven with cryptococcal meningitis, two with toxoplasmosis, and one with progressive multifocal leucoencephalopathy); 22 patients had miscellaneous conditions, including nine with self limiting headache/fever. 62 patients (82%) had normal CSF tau concentration and 14 patients (18%) had elevated tau. In those with HADC, there was no correlation between the degree of dementia or atrophy on magnetic resonance imaging and CSF tau. Elevated CSF tau was associated with poor outcome as six of eight patients who died within 4 weeks of lumbar puncture had elevated tau (p=0.0024, two tailed Fisher's exact test). Conclusions: CSF tau levels are not elevated in the majority of HIV infected patients presenting with acute neurological episodes. CSF tau levels show no correlation with severity of dementia/atrophy on magnetic resonance imaging. Although elevated CSF tau was observed in some patients with conditions causing cerebral necrosis, the finding did not delineate underlying pathology but was associated with poor outcome. Key Words: tau; AIDS; cerebrospinal fluid; dementia; magnetic resonance imaging

Green, A.; Giovannoni, G.; Hall-Craggs, M.; Thompson, E.; Miller, R.



Pseudocholinesterase activity in cerebrospinal fluid as a biomarker of solid central nervous system tumors in children.  


Aim. To determine the activity of pseudocholinesterase (PChE) in cerebrospinal fluid (CSF) and serum in children with solid central nervous system (CNS) tumor and to assess whether PChE activity could be a valid biomarker for solid CNS tumors in children. Methods. The study and control group included 30 children each. Children in the study group had a solid CNS tumor, while those from the control group had never suffered from any tumor diseases. CSF and serum samples were collected from all participants and PChE activity was determined using the Ellman's spectrophotometric method. PChE activity in CSF was shown as a cerebrospinal fluid/serum ratio expressed in percentage, ie, PChE CSF/serum ratio. Receiver operating characteristic (ROC) curve was used to assess whether PChE activity can be used as a biomarker for identifying children with solid CNS tumors. Results. Children with solid CNS tumor had significantly higher PChE activity in CSF and serum, as well as PChE CSF/serum ratio (P=0.001). PChE CSF/serum ratio in the study group was 2.38% (interquartile range [IQR] 1.14-3.97) and 1.09% (IQR 0.95-1.45) in the control group. ROC curve analysis of PChE CSF/serum ratio resulted in an area under the curve (AUC) value of 0.76 (95% confidence interval [CI] 0.63-0.88) and a cut-off of 1.09. Twenty five of 29 patients with elevated PChE CSF/serum ratio had a tumor, corresponding to a sensitivity of 83% and a specificity of 53%. Conclusion. PChE CSF/serum ratio may be used as a test or biomarker with good sensitivity for solid CNS tumors in children. PMID:24170721

Mikecin, Lili; Krizmaric, Miljenko; Stepan Giljevic, Jasminka; Gjurasin, Miroslav; Kern, Josipa; Lenicek Krleza, Jasna; Popovic, Ljiljana



Rapid Determination of Methadone in Plasma, Cerebrospinal Fluid, and Urine by Gas Chromatography and Its Application to Routine Drug Monitoring  

Microsoft Academic Search

Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, cerebrospinal fluid, or urine into n-hexane\\/isoamylalcohol (99\\/1, v\\/v). Dextropropoxyphene was used as internal standard. Separation was achieved with

Norbert Schmidt; Reinhard Sittl; Kay Brune; Gerd Geisslinger



Effects of irregular cerebrospinal fluid production rate in human brain ventricular system  

NASA Astrophysics Data System (ADS)

Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd



Hypothesis on the pathophysiology of syringomyelia based on simulation of cerebrospinal fluid dynamics  

PubMed Central

Objectives: Despite many hypotheses, the pathophysiology of syringomyelia is still not well understood. In this report, the authors propose a hypothesis based on analysis of cerebrospinal fluid dynamics in the spine. Methods: An electric circuit model of the CSF dynamics of the spine was constructed based on a technique of computational fluid mechanics. With this model, the authors calculated how a pulsatile CSF wave coming from the cranial side is propagated along the spinal cord. Results: Reducing the temporary fluid storage capacity of the cisterna magna dramatically increased the pressure wave propagated along the central canal. The peak of this pressure wave resided in the mid-portion of the spinal cord. Conclusions: The following hypotheses are proposed. The cisterna magna functions as a shock absorber against the pulsatile CSF waves coming from the cranial side. The loss of shock absorbing capacity of the cisterna magna and subsequent increase of central canal wall pressure leads to syrinx formation in patients with Chiari I malformation.

Chang, H; Nakagawa, H



Cisterna magna microdialysis of sup 22 Na to evaluate ion transport and cerebrospinal fluid dynamics  

SciTech Connect

Microdialysis is used in vivo for measuring compounds in brain interstitial fluid. The authors describe another application of this technique to the central nervous system, namely microprobe dialysis in the cisterna magna to study the dynamics of ion transport and cerebrospinal fluid (CSF) formation in the rat. The choroid plexus is the major source of CSF, which is produced by active transport of Na from blood into the cerebral ventricles. Formation of CSF is directly proportional to the blood-to-CSF transport of Na. By injecting {sup 22}Na into the systemic circulation and quantifying its movement into CSF by microdialysis, one can reliably estimate alterations in the rate of CSF formation. The sensitivity of this system was determined by administering acetazolamide, a standard inhibitor of CSF production. Because acetazolamide is known to decrease CSF formation by 40% to 50%, the cisternal microdialysis system in animals treated with this drug should detect a corresponding decrease in the amount of {sup 22}Na dialyzed. This hypothesis is supported by the {sup 22}Na uptake curves for control versus treated animals: that is, by the acetazolamide-induced average diminution of about 45% in both the rate and extent of tracer accession to dialysate. Bumetanide, a loop diuretic, reduced by 30% the {sup 22}Na entry into dialysate. Microprobe dialysis of fluid in the cisterna magna is thus a minimally invasive and economical method for evaluating effects of drugs and hormones on the choroid plexus-CSF system.

Knuckey, N.W.; Fowler, A.G.; Johanson, C.E.; Nashold, J.R.; Epstein, M.H. (Brown Univ./Rhode Island Hospital, Providence (USA))



Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease.  


Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. PMID:23868911

Fonteh, Alfred N; Chiang, Jiarong; Cipolla, Matthew; Hale, Jack; Diallo, Fatimatou; Chirino, Alejandra; Arakaki, Xianghong; Harrington, Michael G



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

SciTech Connect

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.

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



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

NASA Astrophysics Data System (ADS)

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.

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



Production and circulation of cerebrospinal fluid with respect to the subarachnoid space of the optic nerve.  


The function of cerebrospinal fluid (CSF) is to protect the brain and optic nerve from mechanical damage, provide nutrition for axons/neurons, and remove of toxic metabilites. CSF is produced mainly by the choroid plexus epithelium and ependymal cells of the ventricles and flows into interconnecting chambers; namely, the cisterns and the subarachnoid spaces. Based on studies of CSF circulation and direction of flow using radioisotopes and other tracers injected into the CSF, it is thought that there is a bulk circulation of fluid from the sites of production in the third, fourth, and lateral ventricles to the arachnoid villi and probably to the lymphatic capillaries in the cranial dura mater. The mechanism by which CSF is propelled is incompletely understood, but probably is influenced by the release of newly produced CSF, ventricular pulsations, and the pulse pressure of the vascular choroid plexus. This mechanism would account for the steady CSF pressure. In addition to the steady CSF pressure, overlapping pressure spikes occur during trunk inclination, coughing and other valsalva. PMID:23733131

Killer, Hanspeter E


[Magnetic resonance in dural post-puncture headache in patient with cerebrospinal fluid hypotension].  


Magnetic resonance imaging (MRI) has allowed us to establish a set of radiologic signs associated with intracranial hypotension syndrome. Findings are partly influenced by cerebral displacement. Intracranial hypotension syndrome is characterized by a decrease in cerebrospinal fluid (CSF) pressure to less than 60 mm H2O associated with occipital headache radiating to the frontal and temporal zones. For diagnostic purposes, the most common cause is anesthetic or therapeutic dural puncture, although spontaneous CSF leakage can occur. CSF protein and lymphocyte counts may be high, while the cranial meninges biopsy is normal. MRI images may show a descended brain, taking the start of the sylvian aqueduct and the location of the cerebellar amygdalae as points of reference; diminished size of the subarachnoidal cisterns and occasionally of the cerebral ventricles; meningeal enhancement from increased uptake of the contrast solution; subdural hygromas and hematomas; and pituitary enlargement. Paraspinal fluid and dilated epidural veins may be observed. Radiologic images and clinical signs are related. When CSF pressure is very low, there is greater meningeal enhancement, subdural collection and cerebral displacement. Findings gradually disappear as symptoms diminish. The signs and symptoms that might develop during intracranial hypotension syndrome vary according to the brain structure that might be affected during descent, repositioning and the traction of anchoring structures. MRI allows the degree of cerebral and spinal involvement to be ascertained, to predict whether resolution of the clinical picture will be early or late and to visualize the effect of approaches to reducing CSF leakage. PMID:12025253

Reina, M A; Alvarez-Linera, J; López, A; Benito-León, J; De Andrés, J A; Sola, R G



Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem  

PubMed Central

Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment.

Orts-Del'Immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jerome



Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem.  


Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment. PMID:22570378

Orts-Del'immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme



Alteration of cystatin C levels in cerebrospinal fluid of patients with Guillain-Barré Syndrome by a proteomical approach  

Microsoft Academic Search

Objective To better understand the pathophysiological mechanisms underlying Guillain-Barré Syndrome (GBS) and to ascertain the protein\\u000a that presents with the most observable changes in the cerebrospinal fluid (CSF) of patients GBS. Methods we analyzed individually the proteomes of CSF of patients with GBS (the experiment group) and control subjects suffering\\u000a from other neurological disorders (the control group) with two-dimensional gel

Yinrong Yang; Shilian Liu; Zhaoyu Qin; Yazhou Cui; Yanjiang Qin; Shumei Bai



High-performance liquid chromatographic method for determination of 2-difluoromethyl- dl-ornithine in plasma and cerebrospinal fluid  

Microsoft Academic Search

A simple, sensitive, selective and reproducible method based on anion-exchange liquid chromatography with post-column derivatisation was developed for the determination of eflornithine (2-difluoromethyl-dl-ornithine; DFMO) in human plasma and cerebrospinal fluid. The 1-alkylthio-2-alkyl-isoindoles fluorescent derivative of the drug was separated from the internal standard (MDL 77246A) on an anion-exchange column (PRP-X300, 250×2.1 mm, 7-?m particle size: Hamilton, USA), with retention times

W Hanpitakpong; B Kamanikom; V Banmairuroi; K Na-Bangchang



An amino acid mixture deficient in phenylalanine and tyrosine reduces cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet monkeys  

Microsoft Academic Search

An amino acid mixture devoid of tryptophan, given orally, was previously shown to reduce cerebrospinal fluid levels of tryptophan\\u000a and 5-hydroxyindoleacetic acid in vervet monkeys, as compared to a control mixture containing all essential amino acids. In\\u000a the present study, we tested the possibility that a similar amino acid mixture containing tryptophan, but devoid of phenylalanine\\u000a and tyrosine (the amino

R. M. Palmour; Frank R. Ervin; Glen B. Baker; Simon N. Young



Cerebrospinal fluid otorrhoea from an abnormal communication between the internal auditory meatus and the medial wall of the tympanic cavity.  


Patients who have had middle-ear or mastoid surgery are at an increased risk of developing cerebrospinal fluid (CSF) otorrhoea. The CSF leak is usually from defects in the tegmen or posterior cranial fossa. We present a patient with CSF otorrhoea following a modified radical mastoidectomy seven years ago. There was an unusual communication between the internal auditory meatus (IAM) and the middle ear. Radiologic imaging like the MRI is useful in identifying the site of leak. PMID:20527282

Philip, R; Prepageran, N; Raman, R; Waran, V



Cerebrospinal fluid levels of tau phosphorylated at threonine 181 in patients with Alzheimer’s disease and vascular dementia  

Microsoft Academic Search

In 31 patients with probable Alzheimer’s disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and\\u000a Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six\\u000a age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis\\u000a and after a

Sabrina Ravaglia; Paola Bini; Elena Sinforiani; Diego Franciotta; Elisabetta Zardini; Pietro Tosca; Arrigo Moglia; Alfredo Costa



Tumor necrosis factor-?, interleukin-1?, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy  

Microsoft Academic Search

There have been few reports describing cytokines in the cerebrospinal fluid (CSF) of patients with spinal degenerative disorders.\\u000a This study investigated whether interleukin-1? (IL-1?), interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?) could be\\u000a detected in CSF of patients with cervical myelopathy or lumbar radiculopathy and whether the concentrations of those cytokines\\u000a correlated with the severity of disease conditions. CSF samples

Hideki Nagashima; Yasuo Morio; Koji Yamane; Yoshiro Nanjo; Ryota Teshima



Concentrations of Metals, ?-Amyloid and Tau-Markers in Cerebrospinal Fluid in Patients with Alzheimer’s Disease  

Microsoft Academic Search

Background\\/Aims: In this study, metal concentrations were related to the levels of well-known Alzheimer markers in cerebrospinal fluid (CSF), such as amyloid-beta (A?), total tau (T-tau) and phosphorylated-tau (P-tau). Methods: Concentrations of 19 metals (Mg, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg and Pb by inductively coupled plasma-mass spectrometry) and

Lars Gerhardsson; Kaj Blennow; Thomas Lundh; Elisabet Londos; Lennart Minthon



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

Microsoft Academic Search

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 and diagnosis of ED-BM. METHODS: In a cohort of 230 consecutive patients in whom external drains had been

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



Cerebrospinal Fluid Concentrations of Somatostatin and Biogenic Amines in Grown Primates Reared by Mothers Exposed to Manipulated Foraging Conditions  

Microsoft Academic Search

Background: In an earlier study, infant primates were nursed by mothers randomly assigned to variable forag- ing demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentra- tions and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations

Jeremy D. Coplan; Ronald C. Trost; Michael J. Owens; Thomas B. Cooper; Jack M. Gorman; Charles B. Nemeroff; Leonard A. Rosenblum



Relationship between presence of vasoconstrictor activity in cerebrospinal fluid and time after subarachnoid haemorrhage from rupture of cerebral arterial aneurysms.  

PubMed Central

The relationship between clinical condition and vasoconstrictor factors in cerebrospinal fluid was studied in 19 patients for up to six weeks after subarachnoid haemorrhage. Vasoconstrictor activity was assayed biologically. Sixteen of 19 patients improved as vasoconstrictor activity declined; this pattern was not significantly influenced by surgery. Serial angiography was performed on three patients and a qualitative relationship was shown between arterial dilatation, clinical improvement, and reduced pharmacological activity.

Hunt, T M; Du Boulay, G H; Blaso, W P; Forster, D M; Boullin, D J



Kinetics of Entry and Distribution of 5Fluorouracil in Cerebrospinal Fluid and Brain following Intravenous Injection in a Primate1  

Microsoft Academic Search

SUMMARY The distribution of systemically or locally administered 5-fluorouracil-2-14C (5-FU) in brain and cerebrospinal fluid (CSF) of the monkey (Macaca mulatta) has been investiga ted. Following controlled i.v. injection, there was rapid penetration of the 5-FU into brain and CSF, concomitant with a rapid loss of 5-FU from the systemic plasma compartment. CSF repeatedly sampled from various sites (lumbar, cisternal,

Robert S. Bourke; Charles R. West; Girish Chheda; Donald B. Tower



Peak B endorphin concentration in cerebrospinal fluid: reduced in chronic pain patients and increased during the placebo response  

Microsoft Academic Search

The level of an endogenous opioid (peak B endorphin) was measured in chromatographically fractionated cerebrospinal fluid (CSF) sampled from two groups of chronic pain patients before and after intrathecal saline (placebo) injection. As assessed by a verbal rating scale, one group reported no change in their level of pain (non-responders, NR;n=6) while the other group reported complete or >50% pain

Jonathan J. Lipman; Barney E. Miller; Kit S. Mays; Merry N. Miller; William C. North; William L. Byrne



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

Microsoft Academic Search

This review addresses recent developments in amyloid beta (Abeta), total tau (t-tau), and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the protection of patients with mild cognitive impairment (MCI) into dementia and the differential diagnosis of Alzheimer's Disease (AD). A combination of Abeta42 and t-tau in CSF can

Suzanne V. Frankfort; Linda R. Tulner; Jos P. C. M. van Campen; Marcel M. Verbeek; Rene W. M. M. Jansen; Jos H. Beijnen



Semiautomatic Analysis of Phase Contrast Magnetic Resonance Imaging of Cerebrospinal Fluid Flow through the Aqueduct of Sylvius  

Microsoft Academic Search

Objective: Quantification of the cerebrospinal fluid (CSF) flow through the aqueduct of Sylvius by means of magnetic resonance imaging\\u000a (MRI) is subject to interobserver variability due to the region of interest (ROI) selection. Our objective is to develop a\\u000a semiautomatic measurement method to achieve reproducible quantitative analysis of CSF flow rate and stroke volume. Material and methods: MR examinations were

Yudy Natalia Flórez; David Moratal; Juana Forner; Luis Martí-Bonmatí; Estanislao Arana; Ulises Guajardo-Hernández; José Millet-Roig



Nano-HPLC–MS analysis of phospholipids in cerebrospinal fluid of Alzheimer’s disease patients—a pilot study  

Microsoft Academic Search

There is emerging evidence that lipids play an important role in many neurodegenerative processes, for example in Alzheimer’s\\u000a disease (AD). Although different lipid alterations in the AD brain have been reported, there have only been very few investigations\\u000a of lipid changes in the cerebrospinal fluid (CSF). Recent developments in mass spectrometry (MS) have enabled fast and sensitive\\u000a detection of lipid

M. Kosicek; S. Kirsch; R. Bene; Z. Trkanjec; M. Titlic; L. Bindila; J. Peter-Katalinic; S. Hecimovic



Healthcare Savings Associated with Reduced Infection Rates Using Antimicrobial Suture Wound Closure for Cerebrospinal Fluid Shunt Procedures  

Microsoft Academic Search

Background\\/Aims\\/Methods: This is a follow-up study from a recent randomized controlled trial conducted at the Women and Children’s Hospital of Buffalo that investigated the use of antimicrobial sutures (AMS) for wound closure during cerebrospinal fluid shunting procedures. Our purpose was to determine the average cost of shunt infections at our institution and estimate the healthcare savings associated with reduced infection

Jonathan Stone; Thomas J. Gruber; Curtis J. Rozzelle



Evaluation of postmortem serum and cerebrospinal fluid growth hormone levels in relation to the cause of death in forensic autopsy  

Microsoft Academic Search

Previous studies have shown that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly lower in\\u000a cases of asphyxia and poisoning than in other groups, whereas ACTH levels in cerebrospinal fluid (CSF) were significantly\\u000a lower for hypothermia and hyperthermia. This study comparatively analyzed growth hormone (GH) levels in serum and CSF in relation\\u000a to cause of death in routine forensic

Takaki Ishikawa; Tomomi Michiue; Hitoshi Maeda



Necessity of Meningococcal ?-Glutamyl Aminopeptidase for Neisseria meningitidis Growth in Rat Cerebrospinal Fluid (CSF) and CSF-Like Medium  

PubMed Central

The growth of a ?-glutamyl aminopeptidase (GGT)-deficient Neisseria meningitidis strain was much slower than that of the parent strain in rat cerebrospinal fluid (CSF) and in a synthetic CSF-mimicking medium, and the growth failure was suppressed by the addition of cysteine. These results suggested that, in the environment of cysteine shortage, meningococcal GGT provided an advantage for meningococcal multiplication by supplying cysteine from environmental ?-glutamyl-cysteinyl peptides.

Takahashi, Hideyuki; Hirose, Kenji; Watanabe, Haruo



IgM quantification in the cerebrospinal fluid of sleeping sickness patients by a latex card agglutination test  

Microsoft Academic Search

Summary An increased IgM concentration in cerebrospinal fluid (CSF), occurring as a consequence of massive intrathecal IgM synthesis, is a marker of interest for diagnosis of the meningo-encephalitic stage in human African trypanosomiasis. However, in current practice, IgM in CSF is not determined because of the lack of a simple and robust test that is applicable in African rural regions

V. Lejon; D. Legros; M. Richer; J. A. Ruiz; V. Jamonneau; P. Truc; F. Doua; N. Dje; F. X. N'Siesi; S. Bisser; E. Magnus; I. Wouters; J. Konings; T. Vervoort; F. Sultan; P. Buscher



Effects of Diazepam on Sleep, Temperature, 5-Hydroxyindoleacetic and Homovanillic Acids in Cisternal Cerebrospinal Fluid of Cats  

Microsoft Academic Search

The effects of diazepam (DZ) (0.3–1.5 mg\\/kg, i.p.) on sleep, cisternal cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), and rectal temperature of cats were examined. The results showed that administration of DZ produced a significant increase (p = 0.02) in slow-wave sleep (SWS) with a peak occurring at a dose of 0.9 mg\\/kg. Further increase

Mindaugas L. Griauzde; Edwin H. Chen



Neuron-Specific Enolase and S100B in Cerebrospinal Fluid After Severe Traumatic Brain Injury in Infants and Children  

Microsoft Academic Search

ABSTRACT. Background. Traumatic brain injury (TBI) is a leading cause of death and disability in chil- dren. Considerable insight into the mechanisms involved in secondary injury after TBI has resulted from analysis of ventricular cerebrospinal fluid (CSF) obtained in chil- dren with severe noninflicted and inflicted TBI (nTBI and iTBI, respectively). Neuron-specific enolase (NSE) is a glycolytic enzyme that is

Rachel Pardes Berger; Mph Mary Clyde Pierce; Stephen R. Wisniewski; P. David Adelson; Robert S. B. Clark; Randy A. Ruppel; Patrick M. Kochanek


Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.  


Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for CJD, tau-protein concentrations in CSF were significantly higher than in two control-groups of patients with other diseases (median 13,153 pg/ml, range 1,533-27,648 pg/ml; P = 0.0001). One group comprised 19 patients who were seen in the same study and were diagnosed as having other dementing diseases (tau concentration: median 558 pg/ml, range 233-1,769 pg/ml). The second control group comprised 13 patients from our hospital with no dementing disease (tau concentration: median 296 pg/ml, range 109-640 pg/ml). We conclude that determination of tau protein levels in CSF is a useful marker for laboratory diagnosis of CJD. PMID:9147407

Otto, M; Wiltfang, J; Tumani, H; Zerr, I; Lantsch, M; Kornhuber, J; Weber, T; Kretzschmar, H A; Poser, S



Cerebrospinal fluid proteomic profiling of HIV-1-infected patients with cognitive impairment.  


Advanced HIV-1 infection is commonly associated with progressive immune suppression and the development of cognitive, motor, and behavior disturbances. In its most severe form, it is diagnosed as HIV-1 associated dementia (HAD) and can progress to profound functional disability and death. Despite prodigious efforts to uncover biomarkers of HAD, none can adequately reflect disease onset or progression. Thus, we developed a proteomics platform for HAD biomarker discovery and used it to perform a pilot study on cerebrospinal fluid (CSF) from HIV-1-infected people with or without HAD. A 2-dimensional electrophoresis (2-DE) map of a HAD CSF proteome was focused on differentially expressed proteins. 2-DE difference gel electrophoresis (2-D DIGE) analysis showed >90 differences in protein spots of which 20 proteins were identified. Differential expression of 6 proteins was validated by Western blot tests and included vitamin D binding protein, clusterin, gelsolin, complement C3, procollagen C-endopeptidase enhancer 1, and cystatin C. We posit that these proteins, alone or together, are potential HAD biomarkers. PMID:17929958

Rozek, Wojciech; Ricardo-Dukelow, Mary; Holloway, Sondra; Gendelman, Howard E; Wojna, Valerie; Melendez, Loyda M; Ciborowski, Pawel



Aquaporin-4 expression in the cerebrospinal fluid in congenital human hydrocephalus  

PubMed Central

Background Aquaporin-4 (AQP4) is a water channel mainly located in the ventricular ependymal cells (brain-CSF barrier), the sub-ependymal glia, glia limitans and in end-feet of astrocytes in at the blood–brain barrier (BBB). Methods In the present work, the expression of AQP4 in the cerebrospinal fluid (CSF) in control and congenital human hydrocephalus infants (obstructive and communicating), was analysed by Western-blot and enzyme immunoassay (ELISA). Results AQP4 was found to be high compared to the control in the CSF in congenital hydrocephalus patients. Western-blot showed higher values for AQP4 than controls in communicating hydrocephalus (communicating: 38.3%, control: 6.9% p?



Understanding the origins of gliomas and developing novel therapies: cerebrospinal fluid and subventricular zone interplay.  


Glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, carries a poor prognosis, with median survival generally less than 1 year. Although initial therapy often eradicates the bulk of the tumor, disease recurrence, usually within 2 cm of the original tumor, is almost inevitable. This may be due to a failure of current therapies to eradicate viable chemotherapy- and radiotherapy-resistant neoplastic progenitor cells, which may then repopulate tumors. An increasing body of preclinical data suggests that these cells may correspond to stem cells derived from the subventricular zone (SVZ), which migrate to tumor sites and contribute to glioma growth and recurrence. Therapeutic targeting of SVZ stem cell populations via cerebrospinal fluid (CSF)-directed therapy may provide a means for limiting tumor recurrence. This approach has proved successful in the treatment of medulloblastoma, another brain tumor thought to be derived from stem cells. We discuss the rationale and design considerations for a clinical trial to evaluate the efficacy of CSF-directed therapy for preventing GBM recurrence. PMID:19660679

Glantz, Michael; Kesari, Santosh; Recht, Lawrence; Fleischhack, Gudrun; Van Horn, Alexis



Effect of clomipramine on monoamine metabolites in the cerebrospinal fluid of behaviorally normal dogs.  

PubMed Central

The tricyclic antidepressant, clomipramine, is an effective treatment for canine compulsive disorder (canine CD). This disorder is a clinical syndrome of abnormal conflict behaviors and its pathophysiology is unknown. However, because clomipramine is an effective treatment, information about the drug's neurochemical effect could enhance the understanding of canine CD. The following experiment used 6 behaviorally normal dogs to assess the effect of clomipramine (3 mg/kg, q24h, PO) on the central turnover of 3 monoamines (serotonin, dopamine, and norepinephrine) as measured by the concentrations of their respective metabolites in cerebrospinal fluid (CSF). In a randomized, placebo-controlled, AB-BA crossover experiment, cisternal CSF was taken after 1, 2, 4, and 6 wk on each treatment. No effect of clomipramine was detected. This contrasts with human studies that have suggested that clomipramine affects the concentrations of monoamine metabolites in lumbar CSF. However, those papers do not address methodological assumptions, such as (i) metabolites in CSF originate only from the brain, and (ii) concentrations of metabolites in cisternal/lumbar CSF reflect the concentrations in local areas of the brain. Notwithstanding the small sample size, our results suggest that more localized sampling techniques (e.g. microdialysis) are needed when examining the effect of drugs on central monoamine metabolites. Clomipramine's efficacy for canine CD indicates the need for neurobiological research and, to our knowledge, our study is the first of its kind in dogs. The resulting data are preliminary but they can inform optimal neurobiological studies of canine CD.

Hewson, C J; Luescher, U A; Parent, J M; Ball, R O



?-Amyloid Peptide Variants in Brains and Cerebrospinal Fluid from Amyloid Precursor Protein (APP) Transgenic Mice  

PubMed Central

In this study, we report a detailed analysis of the different variants of amyloid-? (A?) peptides in the brains and the cerebrospinal fluid from APP23 transgenic mice, expressing amyloid precursor protein with the Swedish familial Alzheimer disease mutation, at different ages. Using one- and two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry, we identified the A? peptides A?(1–40), -(1–42), -(1–39), -(1–38), -(1–37), -(2–40), and -(3–40) as well as minor amounts of pyroglutamate-modified A? (A?(N3pE)) and endogenous murine A? in brains from 24-month-old mice. Chemical modifications of the N-terminal amino group of A? were identified that had clearly been introduced during standard experimental procedures. To address this issue, we additionally applied amyloid extraction in ultrapure water. Clear differences between APP23 mice and Alzheimer disease (AD) brain samples were observed in terms of the relative abundance of specific variants of A? peptides, such as A?(N3pE), A?(1–42), and N-terminally truncated A?(2/3–42). These differences to human AD amyloid were also noticed in a related mouse line transgenic for human wild type amyloid precursor protein. Taken together, our findings suggest different underlying molecular mechanisms driving the amyloid deposition in transgenic mice and AD patients.

Schieb, Heinke; Kratzin, Hartmut; Jahn, Olaf; Mobius, Wiebke; Rabe, Sabine; Staufenbiel, Matthias; Wiltfang, Jens; Klafki, Hans W.



Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation  

PubMed Central

Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein inclusions. Thus, other components in the cell environment likely play a key role in triggering SOD1 toxic aggregation in ALS. Recently, it was found that ALS patients present a specific altered metabolomic profile in the cerebrospinal fluid (CSF) where SOD1 is also present and potentially interacts with metabolites. Here we have investigated how some of these small molecules affect apoSOD1 structure and aggregation propensity. Our results show that as co-solvents, the tested small molecules do not affect apoSOD1 thermal stability but do influence its tertiary interactions and dynamics, as evidenced by combined biophysical analysis and proteolytic susceptibility. Moreover, these compounds influence apoSOD1 aggregation, decreasing nucleation time and promoting the formation of larger and less soluble aggregates, and in some cases polymeric assemblies apparently composed by spherical species resembling the soluble native protein. We conclude that some components of the ALS metabolome that shape the chemical environment in the CSF may influence apoSOD1 conformers and aggregation.

Cristovao, Joana S.; Leal, Sonia S.; Cardoso, Isabel; Gomes, Claudio M.



Derivative spectrophotometric analysis of cerebrospinal fluid for the detection of a ruptured cerebral aneurysm  

NASA Astrophysics Data System (ADS)

A cerebral aneurysm is a weakened portion of an artery in the brain. When a cerebral aneurysm ruptures, a specific type of bleeding known as a subarachnoid hemorrhage (SAH) occurs. No test exists currently to screen people for the presence of an aneurysm. The diagnosis of a SAH is made after an aneurysm ruptures, and the literature indicates that nearly one-third of patients with a SAH are initially misdiagnosed and subjected to the risks associated with aneurysm re-rupture. For those individuals with a suspected SAH, a computerized tomography (CT) scan of the brain usually demonstrates evidence of the bleeding. However, in a considerable portion of people, the CT scan is unable to detect the blood that has escaped from the blood vessel. For circumstances when a SAH is suspected despite a normal CT scan, physicians make the diagnosis of SAH by performing a spinal tap. A spinal tap uses a needle to sample the cerebrospinal fluid (CSF) collected from the patient"s back; CSF is tainted with blood after the aneurysm ruptures. To distinguish between a common headache and a SAH, a fast and an effective solution is required. We describe the development of an effective detection system integrating hardware and a powerful software interface solution. Briefly, CSF from the patient is aspirated and excited with an appropriate wavelength of light. The software employs spectrophotometric analysis of the output spectra and lays the foundation for the development of portable and user-friendly equipment for detection of a ruptured cerebral aneurysm.

Bhadri, P. R.; Majumder, A.; Morgan, C. J.; Pyne, G. J.; Zuccarello, M.; Jauch, E.; Wagner, K. R.; Clark, J. F.; Caffery, J., Jr.; Beyette, Fred R., Jr.



Analysis of cerebrospinal fluid for detection of ruptured cerebral aneurysm using spectrophotometry and signal processing techniques  

NASA Astrophysics Data System (ADS)

An accurate quantification of bilirubin in cerebrospinal fluid (CSF) will provide a simple, sensitive and rapid mechanism for detecting subarachnoid hemorrhage (SAH) and for its differentiation from a traumatic spinal tap. Derivative analysis of the spectrophotometric data provides a model for determining bilirubin in CSF where the primary contaminant is Methemoglobin. Bilirubin values are determined in the range 0-9mg/dl within a methemoglobin concentration of 4.6g/dl using the derivative analysis method. The algorithm is also implemented on test samples in which the bilirubin value is constant (4.6mg/dl) and the methemoglobin varies between 0-9g/dl. The performance of the derivative analysis method is compared to the modified minimum distance method developed in reference one. We suggest a combination of these methods for accurate bilirubin estimation in CSF/hemoglobin. This will provide the foundation for the development of a portable user friendly device for diagnosis of SAH.

Majumder, Anindya; Caffery, James, Jr.; Bhadri, Prashant R.; Beyette, Fred R., Jr.; Clark, Joseph F.; Morgan, Chad J.; Pyne, Gail J.; Zuccarello, Mario; Jauch, Ed; Wagner, Ken R.



Effects of hyperthermia on enzymes and electrolytes in blood and cerebrospinal fluid in dogs  

NASA Astrophysics Data System (ADS)

The effects of exposure to various degrees of heat stress on serum glutamate—oxaloacetate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGPT), alkaline phosphatase (ALK-P-ase), calcium and chlorides have been studied on 75 dogs. Rectal temperature (Tre) was recorded before and after exposure to heat stress. These dogs were divided into 5 groups, according to the Tre level attained after exposure to heat stress. Rectal temperature was raised from normal to 39.45±0.47‡C in the first group, to 40.93±0.17‡C in the second group, to 41.87±0.22‡C in the third group, to 42.90 ± 0.21‡C in the fourth group and to 43.93±0.19‡C in the fifth group. The concentration of enzymes SGOT, SGPT and ALK-P-ase in blood and cerebrospinal fluid (CSF) increased significantly with hyperthermia. Calcium and chlorides concentrations in blood and in CSF tended to increase in hyperthermia. The integrity of the blood brain barrier for these enzymes and calcium is maintained under mild hyperthermia but it breaks down partially under influence of more severe hyperthermia. Core temperature above 41‡C results in damage to tissues and consequential rise of plasma enzymes. This degree of hyperthermia also seems to mark the beginning of injury to blood brain barrier. Critical core temperature tolerated by 50% of animals was 44‡C.

Deswal, K.; Chohan, I. S.



Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson's disease.  


Parkinson's disease (PD) is characterized neuropathologically by the cytoplasmic accumulation of misfolded ?-synuclein in specific brain regions. The endolysosomal pathway appears to be involved in ?-synuclein degradation and, thus, may be relevant to PD pathogenesis. This assumption is further strengthened by the association between PD and mutations in the gene encoding for the lysosomal hydrolase glucocerebrosidase. The objective of the present study was to determine whether endolysosomal enzyme activities in cerebrospinal fluid (CSF) differ between PD patients and healthy controls. Activity levels of 6 lysosomal enzymes (?-hexosaminidase, ?-fucosidase, ?-mannosidase, ?-galactosidase, ?-glucocerebrosidase, and cathepsin D) and 1 endosomal enzyme (cathepsin E) were measured in CSF from 58 patients with PD (Hoehn and Yahr stages 1-3) and 52 age-matched healthy controls. Enzyme activity levels were normalized against total protein levels. Normalized cathepsin E and ?-galactosidase activity levels were significantly higher in PD patients compared with controls, whereas normalized ?-fucosidase activity was reduced. Other endolysosomal enzyme activity levels, including ?-glucocerebrosidase activity, did not differ significantly between PD patients and controls. A combination of normalized ?-fucosidase and ?-galactosidase discriminated best between PD patients and controls with sensitivity and specificity values of 63%. In conclusion, the activity of a number of endolysosomal enzymes is changed in CSF from PD patients compared with healthy controls, supporting the alleged role of the endolysosomal pathway in PD pathogenesis. The usefulness of CSF endolysosomal enzyme activity levels as PD biomarkers, either alone or in combination with other markers, remains to be established in future studies. PMID:23712522

van Dijk, Karin D; Persichetti, Emanuele; Chiasserini, Davide; Eusebi, Paolo; Beccari, Tommaso; Calabresi, Paolo; Berendse, Henk W; Parnetti, Lucilla; van de Berg, Wilma D J



The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review  

PubMed Central

The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships. The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states.



Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease*S?  

PubMed Central

We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brain-specific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins.

Fang, Qiaojun; Strand, Andrew; Law, Wendy; Faca, Vitor M.; Fitzgibbon, Matthew P.; Hamel, Nathalie; Houle, Benoit; Liu, Xin; May, Damon H.; Poschmann, Gereon; Roy, Line; Stuhler, Kai; Ying, Wantao; Zhang, Jiyang; Zheng, Zhaobin; Bergeron, John J. M.; Hanash, Sam; He, Fuchu; Leavitt, Blair R.; Meyer, Helmut E.; Qian, Xiaohong; McIntosh, Martin W.



Metabolomic analysis of cerebrospinal fluid indicates iron deficiency compromises cerebral energy metabolism in the infant monkey.  


Iron deficiency anemia affects many pregnant women and young infants worldwide. The health impact is significant, given iron's known role in many body functions, including oxidative and lipid metabolism, protein synthesis and brain neurochemistry. The following research determined if (1)H NMR spectroscopy-based metabolomic analysis of cerebrospinal fluid (CSF) could detect the adverse influence of early life iron deficiency on the central nervous system. Using a controlled dietary model in 43 infant primates, distinct differences were found in spectra acquired at 600 MHz from the CSF of anemic monkeys. Three metabolite ratios, citrate/pyruvate, citrate/lactate and pyruvate/glutamine ratios, differed significantly in the iron deficient infant and then normalized following the consumption of dietary iron and improvement of clinical indices of anemia in the heme compartment. This distinctive metabolomic profile associated with anemia in the young infant indicates that CSF can be employed to track the neurological effects of iron deficiency and benefits of iron supplementation. PMID:23269483

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



Partial characterization of a novel endogenous opioid in human cerebrospinal fluid  

SciTech Connect

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 but not at higher (>6.0 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.

Miller, B.E.; Lipman, J.J.; Byrne, W.L.



A protocol for the management of canine cerebrospinal fluid for the proteomic assessment of putative biomarkers.  


Cerebrospinal fluid (CSF) is a potential source for disease-specific biomarkers that may assist in the staging and determining the prognosis of neurodegenerative conditions in animals. However, the validity of such putative biomarkers may be influenced by pre-analytical variables, including the procedures adopted to collect and store the CSF. This study assessed the effect of three handling practices on the stability of a panel of CSF proteins: clusterin (also known as apolipoprotein J), haptoglobin, cystatin C, and transthyretin (TTR). The three handling procedures for canine CSF were mimicked in the laboratory as follows: (1) storage in a refrigerator overnight (4°C for 18h); (2) carrying a sample in the pocket of a clinician (37°C for 4h); and (3) mailing a sample to a remote laboratory for analysis (room temp for 48h). The impact of these three scenarios on the concentrations of the selected proteins was assessed using Western blotting and compared to an aliquot of CSF that had been kept frozen. The level of clusterin was significantly reduced following 48h at room temperature (P<0.05), while the concentration of the dimeric form of TTR increased following this handling procedure and also when held at 37°C for 4h. A reducing agent prevented this increase at 37°C. In conclusion, exposing CSF samples to various environmental conditions can significantly alter their protein content, a factor that must be considered in studies assessing potential biomarkers in canine CSF. PMID:23820135

Shafie, Intan N F; Anderson, Thomas J; Penderis, Jacques; Eckersall, Peter D; McLaughlin, Mark



Cerebrospinal fluid antibodies to oxidized LDL are increased in Alzheimer's disease.  


Lipoprotein oxidation may play an important role in the pathogenesis of Alzheimer's Disease (AD), and therefore, we investigated cerebrospinal fluid (CSF) antibodies to oxidized low-density lipoprotein (OxLDL) in patients with AD and other neurodegenerative dementias. IgM and IgG antibody titers to OxLDL were measured in 50 CSF samples and 11 plasma samples using chemiluminescent ELISA. All CSF samples contained IgG antibodies, and also most IgM, binding to OxLDL. CSF antibodies to OxLDL were not related to CSF protein or albumin concentrations or plasma antibodies to OxLDL. Competition immunoassay for specificity demonstrated that about 50% of the CSF IgG binding to OxLDL was inhibited by soluble OxLDL. CSF IgG antibodies to OxLDL were significantly increased in AD patients compared to controls and to patients with frontotemporal lobar degeneration. The role of these antibodies in CSF is unknown and further investigations are needed. PMID:19130885

Kankaanpää, Jari; Turunen, S Pauliina; Moilanen, Virpi; Hörkkö, Sohvi; Remes, Anne M



Peptide repertoire of human cerebrospinal fluid: novel proteolytic fragments of neuroendocrine proteins.  


Polypeptides in human cerebrospinal fluid (CSF), isolated by phase separation in chloroform-methanol-water and reversed-phase HPLC, were characterised by sequence analysis and mass spectrometry. This identified the presence of peptide fragments of testican, neuroendocrine specific protein VGF, neuroendocrine protein 7B2, chromogranin B/secretogranin I, chromogranin A, osteopontin, IGF-II E-peptide and proenkephalin. The majority of these fragments were generated by proteolysis at dibasic sites, suggesting that they are derived by activities related to prohormone convertase(s). Several of the fragments have previously not been detected, and their functions in CSF or elsewhere are unknown. A characteristic feature of all these fragments is a very high content of acidic residues, in particular glutamic acid. In addition to the fragments of neuroendocrine proteins, endothelin-binding receptor-like protein 2, ribonuclease 1, IGF-binding protein 6, albumin, alpha1-acid glycoprotein 1, prostaglandin-H2 D-isomerase, apolipoprotein A1, transthyretin, beta2-microglobulin, ubiquitin, fibrinopeptide A, and C4A anaphylatoxin were found. PMID:11339279

Stark, M; Danielsson, O; Griffiths, W J; Jörnvall, H; Johansson, J



Penetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates.  

PubMed Central

We characterized the cerebrospinal fluid (CSF) penetration and pharmacokinetics of SCH-39304 in adult rhesus monkeys receiving a single oral dose of SCH-39304 (2.0 mg/kg of body weight). The mean CSF-to-plasma area under the curve ratio was 0.63 (+/- 0.18, standard error of the mean); maximum concentrations were 1.34 micrograms/ml (+/- 0.18) in CSF and 1.96 micrograms/ml (+/- 0.43) in plasma. The mean plasma half-life was 45.7 h (+/- 11), and mean CSF half-life was 38.7 h (+/- 3.5). The mean levels of SCH-39304 at 24 h were 1.48 micrograms/ml (+/- 0.3) in plasma and 0.96 microgram/ml (+/- 0.12) in CSF. We conclude that SCH-39304 effectively penetrates into CSF and achieves concentrations considered active against many opportunistic yeasts and that these concentrations are sustained in CSF for greater than or equal to 24 h.

Walsh, T J; Lester-McCully, C; Rinaldi, M G; Wallace, J E; Balis, F M; Lee, J W; Pizzo, P A; Poplack, D G



Detection of viral antigens in cerebrospinal fluid of patients with herpes simplex virus encephalitis.  


Thirty-two cerebrospinal fluid (CSF) samples from eighteen patients with confirmed herpes simplex encephalitis (HSE) were assayed by an indirect enzyme-linked immunosorbent assay (ELISA) for the presence of viral antigens. The results are expressed as an antigen ratio distinguishing between herpes simplex virus (HSV) antigens containing samples and negative samples. Judged by this criterion a positive result was obtained in 33% of the patients. Overall, 25% of the CSF samples from HSE patients were positive. In one out of 33 control patients with other neurological disorders a positive antigen ratio was found. Two or more CSF samples were available from eleven patients. In six of these, the second or later samples showed a decreased antigen ratio when compared to the first CSF sample. An increase of the anti-HSV antibody titer was seen in the CSF of five of these six patients. Five out of six patients with a decreasing antigen ratio had an unfavorable outcome of their encephalitis, while a favorable outcome was seen in four of the five patients with an increasing or steady antigen ratio. A decrease of the antigen ratio in the course of HSE can be explained by the presence of immune complexes in CSF and may indicate a poor prognosis. PMID:3029320

Bos, C A; Olding-Stenkvist, E; Wilterdink, J B; Scheffer, A J



Reduction of thyroxine uptake into cerebrospinal fluid and rat brain by hexachlorobenzene and pentachlorophenol.  


In the present study the effects of hexachlorobenzene (HCB) and the metabolite pentachlorophenol (PCP) were investigated with respect to uptake of thyroxine (T4) into cerebrospinal fluid (CSF) and brain structures of rats. [125I]T4 was taken up into CSF of control rats by a relatively slow process, reaching a steady state after about 3 h. Both repeated dosing of HCB and single doses of PCP caused decreased uptake of [125I]T4 into CSF, total brain tissue as well as specific brain structures, such as occipital cortex, thalamus, and hippocampus. Although HCB-treatment caused a build-up of HCB and PCP levels in serum in brain only HCB was present in significant amounts (16% of the serum level). In CSF, both HCB and PCP concentrations were below detection levels. Separate experiments with PCP showed, however, a dose- and time-dependent uptake of PCP into CSF. The present results indicate that PCP and the parent compound HCB are able to affect brain supply of T4. This may have consequences for an adequate development of the brain or proper brain function in adults. The exact mechanisms of interference of PCP and/or HCB in brain uptake of T4 remain to be established. PMID:7801323

van Raaij, J A; Frijters, C M; Kong, L W; van den Berg, K J; Notten, W R


Cerebrospinal fluid C-reactive protein in the laboratory diagnosis of bacterial meningitis.  


Samples of cerebrospinal fluid from 112 cases of suspected meningitis were tested for the presence of C-reactive protein (CRP), using a qualitative and quantitative slide test. Bacterial meningitis was confirmed in 34 patients, based on CSF and blood culture results, and/or elevated CSF white blood cell (WBC) count and typical biochemical profile. There were 8 patients with early onset, and 3 who had received prior antimicrobial therapy among the 5 neonates, 23 children, and 6 adults with bacterial meningitis. Organisms recovered from CSF, and/or blood, included Haemophilus influenzae 14, Streptococcus pneumoniae 9, Streptococcus group B-5, Staphylococcus aureus 2, E. coli 2 and Klebsiella pneumoniae 1. Slide test was positive for CRP in 33 cases, giving a sensitivity of 97% which compared favourably with elevated CSF protein 33%, decreased CFS glucose 64.7% CSF glucose/blood glucose less than 1/2, 85%, raised CSF WBC 38.2%, raised CSF PMN 61.7%, CSF culture positive 88.2%, and CSF gram-positive 82.5%. Slide test was positive for CRP in 1 of 78 CSF samples negative for bacterial meningitis, giving a specificity of 98%. It was concluded that testing of CSF for CRP is a simple, rapid and accurate method for the laboratory diagnosis of bacterial meningitis, which is particularly appropriate for areas lacking adequate laboratory facilities. PMID:3895817

Macfarlane, D E; Narla, V R



Tick-borne encephalitis is associated with low levels of interleukin-10 in cerebrospinal fluid  

PubMed Central

Tick-borne encephalitis (TBE) is associated with higher morbidity and induces a stronger intrathecal immune activation than most other viral induced meningo-encephalitis. The aim of this study was to investigate cytokine concentrations in cerebrospinal fluid (CSF) and serum in relation to aetiology and clinical course. Cytokines were analysed by Enzyme-linked Immuno Assay (ELISA) from 44 patients with TBE and from 36 patients with aseptic meningo-encephalitis of other aetiology (non-TBE). Significantly increased CSF levels of Interferon-? (IFN-?), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1ra), and soluble CD8 receptor (sCD8) were detected in both cohorts. Tumour necrosis factor-? (TNF-? showed low levels or was not detected in CSF in any group in the acute stage. However, the CSF levels of IL-10 were significantly lower in TBE than in non-TBE cases 0–6 days after onset of encephalitis. The TBE patients with encephalitis had significantly lower IL-10 CSF levels later in the clinical course (day 7–18) than TBE patients with meningeal disease. Increased IFN-? production, but low IL-10 secretion, may be of pathophysiological significance in TBE.

Gunther, Goran; Haglund, Mats; Lindquist, Lars; Forsgren, Marianne; Andersson, Jan; Andersson, Birger; Skoldenberg, Birgit



CXCL13 as a Cerebrospinal Fluid Marker for Neurosyphilis in HIV-infected Patients with Syphilis  

PubMed Central

Background Asymptomatic neurosyphilis is more difficult to diagnose in HIV-infected patients because HIV itself can cause cerebrospinal fluid (CSF) pleocytosis. The proportion of CSF lymphocytes that are B cells is elevated in neurosyphilis, suggesting that the CSF concentration of the B cell chemoattractant, chemokine (C-X-C motif) ligand 13 (CXCL13) concentration may also be elevated. Methods CSF and blood were collected from 199 HIV-infected patients with syphilis and neurosyphilis. Serum and CSF CXCL13 concentrations were determined. Results Patients with neurosyphilis had higher CSF and serum CXCL13 concentrations compared to patients with syphilis but not neurosyphilis. The odds of having symptomatic neurosyphilis were increased by 2.23 fold for every log increase in CSF CXCL13 concentration and were independent of CSF WBC and plasma HIV RNA concentrations, peripheral blood CD4+ T cell count and use of antiretroviral medications. A cut-off of 10 pg/mL CSF CXCL13 had high sensitivity and a cut-off of 250 pg/mL or evidence of intrathecal synthesis of CXCL13 had high specificity for diagnosis of both symptomatic and asymptomatic neurosyphilis. CSF concentrations of CXCL13 declined after treatment for neurosyphilis. Conclusions CSF CXCL13 concentration may be particularly useful for diagnosis of neurosyphilis in HIV-infected patients because it is independent of CSF pleocytosis and markers of HIV disease.

Marra, Christina M.; Tantalo, Lauren C.; Sahi, Sharon K.; Maxwell, Clare L.; Lukehart, Sheila A.



A case of cerebrospinal fluid leak in an infant after spinal anesthesia.  


A 2 month old, 51 kg female infant underwent neuraxial anesthesia for repair of a right inguinal hernia. After two unsuccessful attempts at obtaining free-flowing cerebrospinal fluid (CSF) in the L(3)-L(4) lumbar interspace with a 25-gauge (G) neonatal spinal needle, clear CSF was obtained using a Quincke 22-G needle. After easy aspiration, a total of 0.7 mL of 0.75% hyperbaric bupivicaine was injected intrathecally. Immediately after the spinal block, a caudal epidural block was placed by injecting 2 mL of 0.25% bupivacaine with 1:200,000 using a 22-G Quincke spinal needle. Surgery and recovery were uneventful. Two days later, after a crying spell, a bulging, grape size swelling was noted in the infant's lumbar region. Examination was normal except that her fontanel was mildly depressed when she was upright, and a 1 - 1.5 cm soft, nontender swelling in her lumbar area bulged out when she strained. The bulge resolved over the next 48 hours. In the majority of neonates, CSF leaks into the epidural space after lumbar puncture. In our case, the patient showed CSF accumulation at the site of puncture. PMID:23688958

Allee, Joy I; Goins, Kathryn M; Berde, Charles B; McCann, Mary Ellen



Small molecules present in the cerebrospinal fluid metabolome influence superoxide dismutase 1 aggregation.  


Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein inclusions. Thus, other components in the cell environment likely play a key role in triggering SOD1 toxic aggregation in ALS. Recently, it was found that ALS patients present a specific altered metabolomic profile in the cerebrospinal fluid (CSF) where SOD1 is also present and potentially interacts with metabolites. Here we have investigated how some of these small molecules affect apoSOD1 structure and aggregation propensity. Our results show that as co-solvents, the tested small molecules do not affect apoSOD1 thermal stability but do influence its tertiary interactions and dynamics, as evidenced by combined biophysical analysis and proteolytic susceptibility. Moreover, these compounds influence apoSOD1 aggregation, decreasing nucleation time and promoting the formation of larger and less soluble aggregates, and in some cases polymeric assemblies apparently composed by spherical species resembling the soluble native protein. We conclude that some components of the ALS metabolome that shape the chemical environment in the CSF may influence apoSOD1 conformers and aggregation. PMID:24048249

Cristóvão, Joana S; Leal, Sónia S; Cardoso, Isabel; Gomes, Cláudio M



Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.  


We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis. PMID:10604277

Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D



Radiation-induced spinal cord glioblastoma with cerebrospinal fluid dissemination subsequent to treatment of lymphoblastic lymphoma  

PubMed Central

Background: Radiation-induced glioma arising in the spinal cord is extremely rare. We report a case of radiation-induced spinal cord glioblastoma with cerebrospinal fluid (CSF) dissemination 10 years after radiotherapy for T-cell lymphoblastic lymphoma. Case Description: A 32-year-old male with a history of T-cell lymphoblastic lymphoma presented with progressive gait disturbance and sensory disturbance below the T4 dermatome 10 years after mediastinal irradiation. Gadolinium-enhanced magnetic resonance (MR) imaging revealed an intramedullary tumor extending from the C6 to the T6 level, corresponding to the previous radiation site, and periventricular enhanced lesions. In this case, the spinal lesion was not directly diagnosed because the patient refused any kind of spinal surgery to avoid worsening of neurological deficits. However, based on a biopsy of an intracranial disseminated lesion and repeated immmunocytochemical examination of CSF cytology, we diagnosed the spinal tumor as a radiation-induced glioblastoma. The patient was treated with radiotherapy plus concomitant and adjuvant temozolomide. Then, the spinal tumor was markedly reduced in size, and the dissemination disappeared. Conclusion: We describe our detailed diagnostic process and emphasize the diagnostic importance of immunocytochemical analysis of CSF cytology.

Kikkawa, Yuichiro; Suzuki, Satoshi O; Nakamizo, Akira; Tsuchimochi, Ryosuke; Murakami, Nobuya; Yoshitake, Tadamasa; Aishima, Shinichi; Okubo, Fumihiko; Hata, Nobuhiro; Amano, Toshiyuki; Yoshimoto, Koji; Mizoguchi, Masahiro; Iwaki, Toru; Sasaki, Tomio



Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis  

PubMed Central

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 < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters. 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.



Immunodiagnostic tests on cerebrospinal fluid in the diagnosis of meningoencephalitic Trypanosoma brucei rhodesiense infection.  


Fourteen cerebrospinal fluid (CSF) samples obtained from Rhodesian sleeping sickness patients from the Lambwe Valley at relapse were positive for the presence of anti-trypanosomal antibody by both IFAT and ELISA. The mean optical density (o.d.) in the ELISA test was 0.804 +/- 0.362 and ranged from 0.258 to 1.363. CSF from five patients from the same area without evidence of meningoencephalitis were all negative by ELISA (mean o.d. 0.023 +/- 0.016, range 0.011-0.051). Control CSF samples from U.K. patients without Rhodesian sleeping sickness but with elevated levels of CSF total protein were also negative. Antibody detected by ELISA declined after Mel-B treatment of relapse and most samples had returned to negative within two years of treatment. We present evidence that serological evaluation of the CSF by ELISA and/or IFAT can provide supportive evidence of the trypanosomal origin of the infection. This is especially important at the time of relapse, when parasitological diagnosis may be impossible and records of treatment for the primary infection may not be available. PMID:2694987

Smith, D H; Bailey, J W; Wellde, B T



Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome  

PubMed Central

Background Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS. Methods and Principal Findings Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01). CFS (n?=?43) had 2,783 non-redundant proteins, nPTLS (n?=?25) contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes. Conclusions nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

Schepmoes, Athena A.; Clauss, Therese R.; Adkins, Joshua N.; Camp, David G.; Holland, Bart K.; Bergquist, Jonas; Coyle, Patricia K.; Smith, Richard D.; Fallon, Brian A.; Natelson, Benjamin H.



Cerebrospinal fluid cytokine levels in migraine, tension-type headache and cervicogenic headache.  


Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1beta, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-beta1 (TGF-beta1)] were included. There were significant group differences in IL-1ra, TGF-beta1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-beta1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache. PMID:19175774

Bø, S H; Davidsen, E M; Gulbrandsen, P; Dietrichs, E; Bovim, G; Stovner, L J; White, L R



Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.  


Recent findings indicate that nitric oxide (NO*) over-production might be an important factor in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). We measured significantly higher concentrations of uric acid and thiol group-containing molecules (R-SH groups) in the cerebrospinal fluid (CSF) from SALS patients compared to controls. The above factors, together with a slightly increased free iron concentration found in the CSF, favour conditions necessary for the formation of the dinitrosyl iron complex, capable of NO* bio-transformation. Thus, we performed ex vivo saturation of CSF (from both SALS patients and controls) with NO*. A decrease in the level of R-SH was found. This was more pronounced in the CSF from SALS patients. In the CSF from SALS patients the production of nitrite and hydroxylamine was greater than that observed in the CSF from controls. Moreover, we also found increased Cu,Zn-SOD activity in the CSF from SALS patients (when compared to control subjects) but no activity corresponding to Mn-SOD in any CSF samples. As Cu,Zn-SOD can react with nitroxyl forming NO*, the conditions for a closed, but continuous, loop of NO* biotransformation are present in the CSF of ALS patients. PMID:16354415

Koki?, Aleksandra Nikoli?; Stevi?, Zorica; Stojanovi?, Srdjan; Blagojevi?, Dusko P; Jones, David R; Pavlovi?, Sanja; Niketi?, Vesna; Apostolski, Slobodan; Spasi?, Mihajlo B



Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.  


Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P<0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia. PMID:11029642

Do, K Q; Trabesinger, A H; Kirsten-Krüger, M; Lauer, C J; Dydak, U; Hell, D; Holsboer, F; Boesiger, P; Cuénod, M



Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development.  


Embryonic-cerebrospinal fluid (E-CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E-CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E-CSF contains all-trans-retinol and retinol-binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic-rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E-CSF helps to control RA synthesis in the IsO by means of the RBP and all-trans-retinol it contains; (2) E-CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E-CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. PMID:21594951

Alonso, M I; Martín, C; Carnicero, E; Bueno, D; Gato, A



The characterization of arachnoid cell transport II: paracellular transport and blood-cerebrospinal fluid barrier formation.  


We used an immortalized arachnoid cell line to test the arachnoid barrier properties and paracellular transport. The permeabilities of urea, mannitol, and inulin through monolayers were 2.9 ± 1.1 × 10(-6), 0.8 ± .18 × 10(-6), 1.0 ± .29 × 10(-6)cm/s. Size differential permeability testing with dextran clarified the arachnoidal blood-cerebrospinal fluid (CSF) barrier limit and established a rate of transcellular transport to be about two orders of magnitude slower than paracellular transport in a polyester membrane diffusion chamber. The theoretical pore size for paracellular space is 11Å and the occupancy to length ratio is 0.8 and 0.72 cm(-1) for urea and mannitol respectively. The permeability of the monolayer was not significantly different from apical to basal and vice versa. Gap junctions may have a role in contributing to barrier formation. Although the upregulation of claudin by dexamethasone did not significantly alter paracellular transport, increasing intracellular cAMP decreased mannitol permeability. Calcium modulated paracellular transport, but only selectively with the ion chelator, EDTA, and with disruption of intracellular stores. The blood-CSF barrier at the arachnoid is anatomically and physiologically different from the vascular-based blood-brain barrier, but is similarly subject to modulation. We describe the basic paracellular transport characteristics of this CSF "sink" of the brain which will allow for a better description of mass and constitutive balance within the intracranial compartment. PMID:22814001

Lam, C H; Hansen, E A; Janson, C; Bryan, A; Hubel, A



Avidity of anti-neurocytoskeletal antibodies in cerebrospinal fluid and serum.  


Antibodies have different avidities that can be evaluated using modified enzyme-linked immunosorbent assay (ELISA) techniques. We determined levels and avidities of antibodies to light (NFL) and medium (NFM) subunits of neurofilaments and tau protein in serum and cerebrospinal fluid (CSF) from 26 patients and anti-tau antibody levels and their avidities in 20 multiple sclerosis (MS) patients and 20 age- and sex-matched controls. Each sample was analyzed using both standard ELISA and also using a similar ELISA protocol with the addition of urea. The avidities of anti-neurocytoskeletal antibodies were higher in the CSF than those in serum (anti-NFL, p < 0.0001; anti-tau, p < 0.01; anti-NFM, n.s.). There was no relationship between avidities in serum and CSF for individual anti-neurocytoskeletal antibodies. We did not observe the relationship among the avidities of various anti-neurocytoskeletal antibodies. The avidities of anti-tau antibodies in the CSF were significantly higher in the MS patients than those in the controls (p < 0.0001). The study demonstrates the differences in avidities of CSF or serum neurocytoskeletal antibodies measured as the urea resistance by ELISA method. Avidity determination of anti-neurocytoskeletal antibodies could contribute to the evaluation of the immunological status of patients. PMID:22566118

Fialová, L; Švarcová, J; Bartos, A; Malbohan, I



Cerebrospinal fluid biomarkers in Alzheimer's disease, vascular dementia and ischemic stroke patients: a critical analysis.  


Vascular factors are thought to contribute to the development of disease pathology in neurodegenerative dementia such as Alzheimer's disease (AD). Another entity, called vascular dementia (VaD), comprises a less defined group of dementia patients having various vascular diseases that especially emerge in the elderly population and require valid options for examination and differential diagnosis. In the context of a retrospective study, we analyzed the cerebrospinal fluid (CSF) biomarkers t-tau, p-tau and Aß42 of a total of 131 patients with AD (n = 47), mild cognitive impairment (MCI) (n = 22), VaD (n = 44) and stroke (n = 18). We found a remarkable alteration in CSF biomarker profile in AD, VaD and in acute ischemic events. CSF profile in AD patients was altered in a very similar way as in stroke patients, without statistical differences. In stroke, increase depend largely on size and duration after the initial event. Total tau levels were useful to differ between VaD and stroke. Aß42 decreased in a similar way in AD, VaD and stroke and had a trend to lower levels in MCI but not in controls. PMID:23877436

Kaerst, Lisa; Kuhlmann, Andre; Wedekind, Dirk; Stoeck, Katharina; Lange, Peter; Zerr, Inga



Dural defect repair in translabyrinthine acoustic neuroma surgery and its implications in cerebrospinal fluid leak occurrence.  


Cerebrospinal fluid (CSF) leak is a complication that may occur after translabyrinthine (translab) acoustic neuroma (AN) removal. The aim of this study is to verify the incidence of CSF leak using two techniques for dural defect closure in translab AN surgery and present a new technique for dural repair. A retrospective study was held, reviewing charts of 34 patients in a tertiary neurotologic referral center. Out of these 34 patients that underwent translab AN excision in a 1-year period, 18 had their dural defect repaired using only abdominal fat graft and 16 using synthetic dura substitute (SDS) plus abdominal fat tissue. One patient (5.5%) in the first group had CSF leak and 1 (6.2%) in the second group had CSF leak postoperatively. Our data suggest that there are no significant differences in CSF leak rates using both techniques, although studies in a larger series must be undertaken to conclude it. We believe that the development of some points in the new technique for dural repair can achieve better results and reduce the CSF leak incidence in the translabyrinthine acoustic neuroma surgery in the near future. PMID:24083124

Netto, Aloysio Augusto Tahan de Campos; Colafêmina, José Fernando; Centeno, Ricardo Silva



Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease.  


Alzheimer's disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid ? peptide (A?), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5' and 3' regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner. PMID:22927204

Bekris, Lynn M; Millard, Steve; Lutz, Franziska; Li, Gail; Galasko, Doug R; Farlow, Martin R; Quinn, Joseph F; Kaye, Jeffrey A; Leverenz, James B; Tsuang, Debby W; Yu, Chang-En; Peskind, Elaine R



Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span.  


Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21-100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p = 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p = 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p = 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment. PMID:23639207

Wang, Lucy Y; Murphy, Richard R; Hanscom, Brett; Li, Ge; Millard, Steven P; Petrie, Eric C; Galasko, Douglas R; Sikkema, Carl; Raskind, Murray A; Wilkinson, Charles W; Peskind, Elaine R



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


The axonal cytoskeleton is a finely organized system, essential for maintaining the integrity of the axon. Axonal degeneration is implicated in the pathogenesis of unremitting disability of multiple sclerosis (MS). Purpose of this study is to evaluate levels of cytoskeletal proteins such as neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), and ?-tubulin (?-Tub) isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their correlation with MS clinical indices. CSF levels of cytoskeletal proteins were determined in 51 patients: 33 with MS and 18 with other neurological diseases (OND). NFL, GFAP and ?-Tub II proteins were significantly higher (p < 0.0001) in MS than in OND group; no significant difference (p > 0.05) was found between MS and OND with regard to ?-Tub III. Interestingly, levels of ?-Tub III and NFL were higher in progressive than in remitting MS forms; on the contrary, higher levels of ?-Tub II and GFAP were found in remitting MS forms. However, with the exception of ?-Tub III, all proteins tend to decrease their CSF levels concomitantly with the increasing disability (EDSS) score. Overall, our results might indicate ?-Tub II as a potential candidate for diagnostic and ?-Tub III as a possible prognostic biomarker of MS. Therefore, further analyses are legitimated and desirable. PMID:22362332

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



rmpM Genosensor for Detection of Human Brain Bacterial Meningitis in Cerebrospinal Fluid.  


Human brain bacterial meningitis is a life-threatening disease caused mainly by Neisseria meningitidis, lead to damage of the outer membrane covering (meninges) of brain or even death. The usual methods of diagnosis are either time-consuming or have some limitations. The specific rmpM (reduction-modifiable protein M) virulent gene based genosensor is more sensitive, specific, and can detect N. meningitidis directly from the patient cerebrospinal fluid in 30 min including 1-min response time. 5'-Thiol-labeled single-stranded DNA (ssDNA) probe was immobilized onto screen-printed gold electrode (SPGE) and hybridized with denatured (95 °C) single-stranded genomic DNA (ssG-DNA) for 10 min at 25 °C. The electrochemical response was measured by cyclic voltammetry, differential pulse voltammetry (DPV) and electrochemical impedance using redox indicators. The sensitivity of the genosensor was 9.5087?(?A/cm(2))/ng with DPV and limit of detection was 3 ng/6 ?L ssG-DNA. The immobilization of the ssDNA probe and hybridization with ssG-DNA from N. meningitidis was characterized by atomic force microscopy and Fourier transform infrared spectroscopy. The rmpM genosensor was stable for 6 months at 4 °C with 10 % loss in initial DPV current. The advantage of rmpM genosensor is to detect bacterial meningitis simultaneously in multiple patients using SPGE array during an outbreak of the disease. PMID:23824531

Dash, Sandip Kumar; Sharma, Minakshi; Khare, Shashi; Kumar, Ashok



Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).  


Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious complication in patients with acute leukemia. One of the major problems of this complication is the diagnosis process itself. CSF cytology is currently considered the gold standard for establishing the diagnosis, a technique which presents various processing limitations, seriously impacting the predictive values. In the last 11 years, studies of CSF flow cytometry analysis done in patients with acute leukemia have demonstrated superiority in comparison with CSF cytology. Although comparative studies between these two techniques have been reported since 2001, no new consensus or formal changes to the gold standard have been established for the CSF acute leukemia diagnosis. The evidence suggests that positive flow cytometry cases, considered as indeterminate cases, will behave like disease in the central nervous system (CNS). Nevertheless, we think there are some variables and considerations that must be first evaluated under research protocols before CNS relapse can be established with only one positive flow cytometry analysis in the setting of indeterminate CSF samples. This paper proposes a diagnostic algorithm and complementary strategies. PMID:22639108

Crespo-Solis, Erick; López-Karpovitch, Xavier; Higuera, Jesús; Vega-Ramos, Beatriz



The utility of cerebrospinal fluid for the molecular diagnosis of toxoplasmic encephalitis.  


The aim of this study was to assess the efficacy of nested polymerase chain reaction (PCR) and the loop-mediated isothermal amplification (LAMP) assay, which were developed to detect and identify toxoplasma parasites in human cerebrospinal fluid (CSF). Nested PCR was performed using primers generated by Dr. L.D. Sibley to target the 18S rDNA instead of the conventionally used primers which target the B1 gene. We also designed Toxoplasma gondii-specific LAMP primers targeting both genes. In vitro detection sensitivity was evaluated using 10-fold serially diluted genomic DNA purified from RH tachyzoites, and clinical sensitivity and specificity were evaluated using clinical CSF samples from 16 patients with toxoplasmic encephalitis (TE) and from 12 patients with other diseases. The 18S rDNA nested PCR showed the highest detection sensitivity limit with a minimum of 1.0 × 10(-8) ng/?L. However, sensitivity and specificity of nested PCR with clinical specimens were 50% and 100%, respectively. The sensitivity of molecular diagnosis of TE is not sufficient; therefore, patients clinically suspected of having TE should be treated promptly. Our molecular diagnostic tool would restrictively facilitate a definitive diagnosis of TE at an early stage in approximately 50% of patients. PMID:23219229

Mikita, Kei; Maeda, Takuya; Ono, Takeshi; Miyahira, Yasushi; Asai, Takashi; Kawana, Akihiko



Clinical characteristics of patients with Epstein Barr virus in cerebrospinal fluid  

PubMed Central

Background The role of Epstein-Barr (EBV) virus in central nervous system (CNS) infections is not fully resolved. It is clearly associated with lymphoproliferative disease of immunosuppressed persons, and may cause encephalitis. Methods We reviewed the medical records, imaging and laboratory findings of all patients EBV DNA PCR positive in cerebrospinal fluid (CSF) during 2000 to 2009 in the Helsinki University Central Hospital. Results We identified 32 patients with EBV DNA in CSF. 11 had history of allogeneic hematopoietic stem cell transplantation, 7 solid organ transplantation and 5 HIV/AIDS. 5 patients had no preceding immunodeficiency. In 8 of the cases, another pathogen was identified in CSF. These were M. tuberculosis (2), T. gondii (2), Aspergillus (1), Herpes simplex virus 1 (1), C. neoformans (1) and Human herpesvirus 6 (1). Altogether in 15/32 (47%) of the cases the clinician had a strong suspicion of cause other than EBV for the patients' CNS symptoms/findings. Of note, 7 of 11 (64%) patients with stem cell transplantation had encephalitis (univariate odds ratio 5.6; confidence Interval 1.1-27.4). Of these 6 had no other pathogen identified. Conclusions EBV DNA was often found together with other microbial findings in CSF of immunocompromised patients. EBV seems to be associated with encephalitis in stem cell transplant recipients.



Biodegradable Polymer Releasing Antibiotic Developed for Drainage Catheter of Cerebrospinal Fluid: In Vitro Results  

PubMed Central

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.

Han, Song Yup; Cho, Ki Hong; Cho, Han Jin; An, Jeong Ho; Ra, Young Sin



Tau proteins in the cerebrospinal fluid of patients with subacute sclerosing panencephalitis.  


Neurodegenerative diseases characterized by cytoskeletal deformation and neurofibrillary tangles are associated with altered levels of tau and related proteins in cerebrospinal fluid (CSF). Neuronal or glial fibrillary tangles have been shown in 20% of subacute sclerosing panencephalitis (SSPE) patients. We therefore investigated CSF samples from 60 newly diagnosed SSPE and 31 neurological control patients for total tau (t-tau), phosphorylated tau (p-tau), and S100-B levels by ELISA. There was no difference between patient and control groups in t-tau and S100-B levels. p-Tau was lower in the SSPE group (p=0.009). Past history of measles infection, measles immunization status, latent period between measles and onset of SSPE, duration of symptoms, frequency of myoclonia, neurological deficit index, stage and progression rate of the disease, CSF glucose levels and cell counts, CSF and serum measles IgG titer, distribution of lesions on brain magnetic resonance imaging were not related to t-tau, p-tau and S100-B levels. Mental status and age were negatively correlated with t-tau, and male gender and EEG abnormalities were associated with higher t-tau levels. The levels of tau proteins in our patients suggest there is no, or only scarce and immature, neurofibrillary tangle formation in SSPE. Autopsy studies showing neurofibrillary tangles might have examined older patients with longer disease and more parenchymal involvement. PMID:20031357

Yuksel, Deniz; Yilmaz, Deniz; Uyar, Neval Y; Senbil, Nesrin; Gurer, Yavuz; Anlar, Banu



Cerebrospinal Fluid Metabolome in Mood Disorders-Remission State has a Unique Metabolic Profile  

PubMed Central

Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion.

Kaddurah-Daouk, Rima; Yuan, Peixiong; Boyle, Stephen H.; Matson, Wayne; Wang, Zhi; Zeng, Zhao Bang; Zhu, Hongjie; Dougherty, George G.; Yao, Jeffrey K.; Chen, Guang; Guitart, Xavier; Carlson, Paul J.; Neumeister, Alexander; Zarate, Carlos; Krishnan, Ranga R.; Manji, Husseini K.; Drevets, Wayne



Proteome analysis of human cerebrospinal fluid as a diagnostic biomarker in patients with meningioma  

PubMed Central

Summary Background To identify meningioma-specific proteins, cerebrospinal fluid (CSF) from 4 patients with a meningioma and 4 patients with a non-brain tumorous lesion were analyzed. Material/Methods Two-dimensional electrophoresis and electrospray quadrupole time-of-flight tandem mass spectrometry analyses revealed 10 unique spots, containing 11 independent proteins (spot #2 and #4 each contained 2 proteins and spot #3 was not identified) were evident in CSF associated with human meningioma: serum albumin precursor (3 different isoforms), Apolipoprotein E (Apo E), Apolipoprotein J precursor (Apo J), Transthyretin precursor (TTR), Prostaglandin D2 synthase 21kDa (PTGDS), proapolipoprotein, Chain D hemoglobin Ypsilanti, alpha-1-antitrypsin (AAT), and beta-2-microglobulin precursor (?2M). Results The contents of Apo E, Apo J and AAT were increased, while PTGDS, TTR and ?2M were decreased. Conclusions The results observed by 2-dimensional electrophoresis were verified by Western blot analysis. The unique proteins may represent possible candidate biomarkers of meningioma.

Kim, Jae Ho; Lee, Sang Kwang; Yoo, Yong Cheol; Park, Nam Hyun; Park, Dan Bi; Yoo, Jong Shin; An, Hyun Joo; Park, Young Mok; Cho, Kyung Gi



Gender-dependent levels of hyaluronic acid in cerebrospinal fluid of patients with neurodegenerative dementia.  


Numerous reports over the years have described neuroinflammatory events and vascular changes in neurodegenerative diseases such as Alzheimers disease (AD) and Dementia with Lewy bodies (DLB). Interestingly, recent reports from other research areas suggest that inflammatory and vascular processes are influenced by gender. These findings are intriguing from the perspective that women show a higher incidence of AD and warrant investigations on how gender influences various processes in neurodegenerative dementia. In the current study we measured the cerebrospinal fluid (CSF) and plasma concentrations of hyaluroinic acid (HA), an adhesionmolecule known to regulate both vascular and inflammatory processes, in AD and DLB patients as well as in healthy elders. Our analysis showed that male AD and DLB patients had almost double the amount of HA compared to female patients whereas no gender differences were observed in the controls. Furthermore, we found that CSF levels of HA in foremost female AD patients correlated with various AD related biomarkers. Correlations between HA levels and markers of inflammation and vascular changes were only detected in female AD patients but in both male and female DLB patients. We conclude that HA may be linked to several pathological events present in AD, as reflected in CSF protein concentrations. The HA profile in CSF, but not in plasma, and associations to other markers appear to be gender-dependent which should be taken into account in clinical examinations and future biomarker studies. PMID:22191565

Nielsen, Henrietta M; Palmqvist, Sebastian; Minthon, Lennart; Londos, Elisabet; Wennström, Malin



A Luminex Assay Detects Amyloid ? Oligomers in Alzheimer's Disease Cerebrospinal Fluid  

PubMed Central

Amyloid beta (a?) protein assembles into larger protein aggregates during the pathogenesis of Alzheimer’s disease (AD) and there is increasing evidence that soluble a? oligomers are a critical pathologic species. Diagnostic evaluations rely on the measurement of increased tau and decreased a?42 in the cerebrospinal fluid (CSF) from AD patients and evidence for oligomeric a? in patient CSF is conflicting. In this study, we have adapted a monoclonal single antibody sandwich ELISA assay to a Luminex platform and found that this assay can detect oligomerized a?42 and sAPP? fragments. We evaluated oligomeric a? reactivity in 20 patients with AD relative to 19 age matched controls and compared these values with a commercially available Alzbio3 kit that detects tau, phosphorylated tau and a?42 on the same diagnostic platform. We found that CSF samples of patients with AD had elevated a? oligomers compared to control subjects (p < 0.05) and the ratio of a? oligomers to a?42 was also significantly elevated (p < 0.0001). Further research to develop high sensitivity analytical platforms and rigorous methods of developing stable assay standards will be needed before the analysis of oligomeric a? becomes a routine diagnostic assay for the evaluation of late onset AD patients.

Herskovits, Adrianna Z.; Locascio, Joseph J.; Peskind, Elaine R.; Li, Ge; Hyman, Bradley T.



Elevated cerebrospinal fluid neopterin concentration is associated with disease severity in acute Puumala hantavirus infection.  


Nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) is the most common hemorrhagic fever with renal syndrome (HFRS) in Europe. The infection activates immunological mechanisms that contribute to the pathogenesis and characteristics of the illness. In this study we measured cerebrospinal fluid (CSF) neopterin concentration from 23 acute-phase NE patients. We collected data on kidney function, markers of tissue permeability, haemodynamic properties, blood cell count, length of hospitalisation, inflammatory parameters, and ophthalmological properties. The neopterin levels were elevated (> 5.8?nmol/L) in 22 (96%) NE-patients (mean 45.8?nmol/L); these were especially high in patients with intrathecal PUUV-IgM production (mean 58.2?nmol/L, P = 0.01) and those with elevated CSF protein concentrations (mean 63.6?nmol/L, P < 0.05). We also observed a correlation between the neopterin and high plasma creatinine value (r = 0.66, P = 0.001), low blood thrombocyte count (r = -0.42, P < 0.05), and markedly disturbed refractory properties of an eye (r = 0.47, P < 0.05). Length of hospitalisation correlated with the neopterin (r = 0.42, P < 0.05; male patients r = 0.69, P < 0.01). Patients with signs of tissue oedema and increased permeability also had high neopterin concentrations. These results reinforce the view that PUUV-HFRS is a general infection that affects the central nervous system and the blood-brain barrier. PMID:23983770

Hautala, Timo; Partanen, Terhi; Sironen, Tarja; Rajaniemi, Saara-Mari; Hautala, Nina; Vainio, Olli; Vapalahti, Olli; Kauma, Heikki; Vaheri, Antti



Unilateral Endoscopic Approach for Repair of Frontal Sinus Cerebrospinal Fluid Leak  

PubMed Central

Cerebrospinal fluid (CSF) leak closure remains one of the most difficult surgeries for skull base surgeons, particularly with frontal sinus involvement. Technological advances in endoscopic surgery increasingly allow for less morbid approaches to the frontal sinus. We describe a series of patients who underwent endoscopic frontal sinus CSF leak repair utilizing a unilateral approach, to evaluate the utility and outcomes of this method. We performed a retrospective review of four cases in tertiary care centers. Participants included patients with CSF leak involving the frontal sinus. Main outcome measures included cessation of CSF leak and frontal sinus patency. Three patients were closed on the first surgical attempt; one with a communicating hydrocephalus required a revision procedure. Leak etiologies included prior craniotomy for frontal sinus mucopyocele, spontaneous meningoencephalocele, erosion due to mucormycosis, and prior endoscopic sinus surgery. The frontal sinus remained patent in three of four patients. No patients have evidence of a leak at a minimum of 1 year after surgery. The repair of frontal sinus CSF leaks is possible in specific cases with an endoscopic unilateral approach in leaks with multiple etiologies. Surgeons should consider this approach when selecting the appropriate procedure for repair of frontal sinus CSF leaks.

Roehm, Corrie E.; Brown, Seth M.



Identification of novel biomarker candidates by differential peptidomics analysis of cerebrospinal fluid in Alzheimer's disease.  


The objective of this work was the application of peptidomics technologies for the detection and identification of reliable and robust biomarkers for Alzheimer's disease (AD) contributing to facilitate and further improve the diagnosis of AD. Using a new method for the comprehensive and comparative profiling of peptides, the differential peptide display (DPD), 312 cerebrospinal fluid (CSF) samples from AD patients, cognitively unimpaired subjects and from patients suffering from other primary dementia disorders were analysed as four independent analytical sets. By combination with a cross validation procedure, candidates were selected from a total of more than 6,000 different peptide signals based on their discriminating power. Twelve candidates were identified using mass-spectrometric techniques as fragments of the possibly neuroprotective neuroendocrine protein VGF and another one as the complement factor C3 descendent C3f. The combination of peptide profiling and cross validation resulted in the detection of novel potential biomarkers with remarkable robustness and a close relation to AD pathophysiology. PMID:16464167

Selle, Hartmut; Lamerz, Jens; Buerger, Katharina; Dessauer, Andreas; Hager, Klaus; Hampel, Harald; Karl, Johann; Kellmann, Markus; Lannfelt, Lars; Louhija, Jukka; Riepe, Matthias; Rollinger, Wolfgang; Tumani, Hayrettin; Schrader, Michael; Zucht, Hans-Dieter



Genetic Variation and Cerebrospinal Fluid Levels of Mannose Binding Lectin in Pneumococcal Meningitis Patients  

PubMed Central

It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05–64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39–3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.

Brouwer, Matthijs C.; Baas, Frank; van der Ende, Arie; van de Beek, Diederik



Genetic variation and cerebrospinal fluid levels of mannose binding lectin in pneumococcal meningitis patients.  


It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05-64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39-3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis. PMID:23741476

Brouwer, Matthijs C; Baas, Frank; van der Ende, Arie; van de Beek, Diederik



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

PubMed Central

Background: The pathogenesis of posthaemorrhagic hydrocephalus (PHHC) following intraventricular haemorrhage (IVH) in premature infants includes a fibroproliferative reaction leading to arachnoidal fibrosis, ultimately causing malresorption of cerebrospinal fluid (CSF) at the arachnoid villi. Aims: To determine whether an increased concentration of the carboxyterminal propeptide of type I procollagen (PICP) in the CSF of neonates after IVH reflects the activation of collagen synthesis preceding the manifestation of PHHC. Methods: From 20 neonates with PHHC (median birth weight 740 g, median gestational age 25+1 weeks), 52 CSF samples were collected. CSF samples of four neonates (median birth weight 2170 g, median gestational age 32+4 weeks) with congenital non-haemorrhagic hydrocephalus served as controls. PICP was measured by radioimmunoassay. Results: PICP in CSF taken at the start of external CSF drainage (median day 21, range 17–25 days postnatal age) was significantly increased (median 851.5, range 153.5–1944 µg/l) compared with controls (median 136.1, range 33.8–169.5 µg/l). CSF concentrations of PICP declined until permanent shunt placement (median day 70, range days 41–113). Conclusion: In neonates who develop PHHC, significant elevation of PICP concentration in the CSF is present 3–4 weeks after IVH. It reflects the increase of local type I collagen turnover, thereby correlating with manifestation of PHHC.

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



Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis  

PubMed Central

We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system [CNS] shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and an additional 220 CSF specimens with positive cultures in which the organism isolated was judged to be a contaminant. Because 121 of these contaminants were isolated in broth only, elimination of the broth culture would decrease unnecessary work. However, 25% of the meningitis associated with CNS shunts would have been missed by this practice. The most common cause of meningitis was Cryptococcus neoformans, followed by Streptococcus pneumoniae and Neisseria meningitidis. In 48 of 56 (88%) of cases, examination of the Gram-stained specimen revealed the causative organism. If patients who had received effective antimicrobial therapy prior to lumbar puncture are excluded, the CSF Gram stain is 92% sensitive. Microscopic examination incorrectly suggested the presence of organisms in only 3 of 2,635 (0.1%) CSF examinations. Thus, microscopic examination of Gram-stained, concentrated CSF is highly sensitive and specific in early diagnosis of bacterial or fungal meningitis.

Dunbar, Sherry A.; Eason, Rachel A.; Musher, Daniel M.; Clarridge, Jill E.



Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease  

PubMed Central

Objectives: To compare cerebrospinal fluid (CSF) total homocysteine and MMA in elderly subjects, patients with Alzheimer's disease, and younger healthy controls. Subjects: CSF samples were obtained from 33 patients under 20 years of age; 28 patients aged 21 to 60 years; 22 normal elderly subjects aged over 60; and 38 Alzheimer patients aged over 60. Results: CSF total homocysteine increased with age (mean (SD): 57 (35) nmol/l in the youngest group v 123 (89) nmol/l in the elderly group (p<0.001)) There was no difference between the elderly group and Alzheimer patients (115 (62) nmol/l). CSF MMA did not differ in the elderly group and the Alzheimer group (38 (13) v 35 (14) ng/ml). In the youngest group, it was significantly higher (60 (15) ng/ml). Conclusions: CSF total homocysteine is not increased in Alzheimer's disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level.

Serot, J; Barbe, F; Arning, E; Bottiglieri, T; Franck, P; Montagne, P; Nicolas, J



Cerebrospinal fluid-based kinetic biomarkers of axonal transport in monitoring neurodegeneration.  


Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid-based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2H2O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson's disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects. PMID:22922254

Fanara, Patrizia; Wong, Po-Yin A; Husted, Kristofor H; Liu, Shanshan; Liu, Victoria M; Kohlstaedt, Lori A; Riiff, Timothy; Protasio, Joan C; Boban, Drina; Killion, Salena; Killian, Maudi; Epling, Lorrie; Sinclair, Elisabeth; Peterson, Julia; Price, Richard W; Cabin, Deborah E; Nussbaum, Robert L; Brühmann, Jörg; Brandt, Roland; Christine, Chadwick W; Aminoff, Michael J; Hellerstein, Marc K



Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia  

PubMed Central

Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinal fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (?2 = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder.

Karlsson, Hakan; Bachmann, Silke; Schroder, Johannes; McArthur, Justin; Torrey, E. Fuller; Yolken, Robert H.



Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.  


To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from Bri2, were significantly associated with patients having cerebellar dysfunction and cognition impairment. Furthermore, expression levels of Bri2 were specifically decreased in the cerebellum compared to other areas of same brain in MS but not in controls, suggesting that decreased cerebellar Bri2 expression may play a role in cerebellar dysfunction. The association with cognition impairment is also of interest because Bri2 is linked to the amyloid processing pathway in the brain. CSF levels of Bri2-23 may serve as a biomarker of these functions in MS and merits further investigation. PMID:20600910

Harris, Violaine K; Diamanduros, Andrew; Good, Pamela; Zakin, Elina; Chalivendra, Varun; Sadiq, Saud A



Tau Phosphorylation Pathway Genes and Cerebrospinal Fluid Tau Levels in Alzheimer's Disease  

PubMed Central

Alzheimer’s disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid ? peptide (A?), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5? and 3? regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner.

Bekris, Lynn M.; Millard, Steve; Lutz, Franziska; Li, Gail; Galasko, Doug R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby W.; Yu, Chang-En; Peskind, Elaine R.



Elimination kinetics of domoic acid from the brain and cerebrospinal fluid of the pregnant rat.  


Domoic acid (DA) causes neurological effects in multiple species upon exposure, including status epilepticus in pregnant sea lions and an epileptic disease state that commonly develops in juveniles. This study aims to define brain toxicokinetic parameters in the pregnant rat in the larger context of maternal-fetal toxin transfer. Specifically, Sprague-Dawley rats were exposed to a low observable effect level of 1.0 mg DA/kg intravenously at gestational day 20, and plasma, brain, and cerebrospinal fluid (CSF) samples were taken at discrete time points over 24 h. Domoic acid concentrations were determined by a tandem LC/MS method recently optimized for brain tissue and CSF. Data showed that 6.6% of plasma DA reached the brain, 5.3% reached the CSF, and DA levels were nearly identical in both brain and CSF for 12 h, remaining above the threshold to activate isolated hippocampal neurons for 2 h. The calculated terminal half-life of CSF was 4 h, consistent with the time for complete CSF regeneration, suggesting that CSF acts as a mechanism to clear DA from the brain. PMID:23134453

Maucher Fuquay, Jennifer; Muha, Noah; Wang, Zhihong; Ramsdell, John S



Cerebrospinal fluid ferritin level, a sensitive diagnostic test in late-presenting subarachnoid hemorrhage.  


The workup of patients with suspected subarachnoid hemorrhage (SAH) presenting late is complicated by a loss of diagnostic sensitivity of computed tomography (CT) brain imaging and cerebrospinal fluid (CSF) bilirubin levels. In this prospective longitudinal study of CSF ferritin levels in SAH, serial CSF samples from 14 patients with aneurysmal SAH requiring extraventricular drainage (EVD) were collected. The control group comprised 44 patients presenting with headache suspicious of SAH. Nine patients underwent a traumatic spinal tap. CSF ferritin levels were significantly higher in the patients with SAH compared with controls (P < .0001). The upper reference range of CSF ferritin is 12 ng/mL, and there was no significant difference between the traumatic and normal spinal taps (mean, 9.0 ng/mL vs 3.9 ng/mL; P = .59). CSF ferritin levels increased after SAH, from an average of 65 ng/mL on day 1 to 1750 ng/mL on day 11 (P < .01). Both the Fisher and Columbia CT scores were significantly correlated with CSF ferritin level. The increase in CSF ferritin level after SAH and possibly may provide additional diagnostic information in patients with suspected SAH who present late to the clinic. PMID:20719531

Petzold, Axel; Worthington, Viki; Appleby, Ian; Kerr, Mary E; Kitchen, Neil; Smith, Martin



Evaluating Amyloid-? Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer's Disease  

PubMed Central

The current study evaluated amyloid-? oligomers (A?o) in cerebrospinal fluid as a clinical biomarker for Alzheimer’s disease (AD). We developed a highly sensitive A?o ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized A? with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic A?o levels. Three clinical materials of well characterized AD patients (n?=?199) and cognitively healthy controls (n?=?148) from different clinical centers were included, together with a clinical material of patients with MCI (n?=?165). A?o levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased A?o levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable A?o levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.

Holtta, Mikko; Hansson, Oskar; Andreasson, Ulf; Hertze, Joakim; Minthon, Lennart; Nagga, Katarina; Andreasen, Niels; Zetterberg, Henrik; Blennow, Kaj



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


Accurate ante mortem diagnosis in frontotemporal lobar degeneration (FTLD) is crucial to the development and implementation of etiology-based therapies. Several neurodegenerative disease-associated proteins, including the major protein constituents of inclusions in Alzheimer's disease (AD) associated with amyloid-beta (A?(1-42)) plaque and tau neurofibrillary tangle pathology, can be measured in cerebrospinal fluid (CSF) for diagnostic applications. Comparative studies using autopsy-confirmed samples suggest that CSF total-tau (t-tau) and A?(1-42) levels can accurately distinguish FTLD from AD, with a high t-tau to A?(1-42) ratio diagnostic of AD; however, there is also an urgent need for FTLD-specific biomarkers. These analytes will require validation in large autopsy-confirmed cohorts and face challenges of standardization of within- and between-laboratory sources of error. In addition, CSF biomarkers with prognostic utility and longitudinal study of CSF biomarker levels over the course of disease are also needed. Current goals in the field include identification of analytes that are easily and reliably measured and can be used alone or in a multi-modal approach to provide an accurate prediction of underlying neuropathology for use in clinical trials of disease modifying treatments in FTLD. To achieve these goals it will be of the utmost importance to view neurodegenerative disease, including FTLD, as a clinicopathological entity, rather than exclusively a clinical syndrome. PMID:23440936

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



Cerebrospinal Fluid B Cells Correlate with Early Brain Inflammation in Multiple Sclerosis  

PubMed Central

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.

Kuenz, Bettina; Lutterotti, Andreas; Ehling, Rainer; Gneiss, Claudia; Haemmerle, Monika; Rainer, Carolyn; Deisenhammer, Florian; Schocke, Michael; Berger, Thomas; Reindl, Markus



Cerebrospinal fluid-based kinetic biomarkers of axonal transport in monitoring neurodegeneration  

PubMed Central

Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid–based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2H2O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson’s disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects.

Fanara, Patrizia; Wong, Po-Yin A.; Husted, Kristofor H.; Liu, Shanshan; Liu, Victoria M.; Kohlstaedt, Lori A.; Riiff, Timothy; Protasio, Joan C.; Boban, Drina; Killion, Salena; Killian, Maudi; Epling, Lorrie; Sinclair, Elisabeth; Peterson, Julia; Price, Richard W.; Cabin, Deborah E.; Nussbaum, Robert L.; Bruhmann, Jorg; Brandt, Roland; Christine, Chadwick W.; Aminoff, Michael J.; Hellerstein, Marc K.



Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.  


Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal through the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild-type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner. PMID:24042041

Cabral, A; Fernandez, G; Perello, M



The utility of cerebrospinal fluid analysis in patients with multiple sclerosis.  


Diagnosis of multiple sclerosis (MS) requires the exclusion of other possible diagnoses. For this reason, the cerebrospinal fluid (CSF) should be routinely analysed in patients with a first clinical event suggestive of MS. CSF analysis is no longer mandatory for diagnosis of relapsing-remitting MS, as long as MRI diagnostic criteria are fulfilled. However, caution is required in diagnosing MS in patients with negative MRI findings or in the absence of CSF analysis, as CSF investigation is useful to eliminate other causes of disease. The detection of oligoclonal IgG bands in CSF has potential prognostic value and is helpful for clinical decision-making. In addition, CSF analysis is important for research into the pathogenesis of MS. Pathophysiological and neurodegenerative findings of inflammation in MS have been derived from CSF investigations. Novel CSF biomarkers, though not yet validated, have been identified for diagnosis of MS and for ascertaining disease activity, prognosis and response to treatment, and are likely to increase in number with modern detection techniques. In this Review, we summarize CSF findings that shed light on the differential diagnosis of MS, and highlight the potential of novel biomarkers for this disease that could advance understanding of its pathophysiology. PMID:23528543

Stangel, Martin; Fredrikson, Sten; Meinl, Edgar; Petzold, Axel; Stüve, Olaf; Tumani, Hayrettin



Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier  

SciTech Connect

Unidirectional flux of /sup 125/I-labeled DSIP at the blood-tissue interface of the blood-cerebrospinal fluid (CSF) barrier was studied in the perfused in situ choroid plexuses of the lateral ventricles of the sheep. Arterio-venous loss of /sup 125/I-radioactivity suggested a low-to-moderate permeability of the choroid epithelium to the intact peptide from the blood side. A saturable mechanism with Michaelis-Menten type kinetics with high affinity and very low capacity (approximate values: Kt = 5.0 +/- 0.4 nM; Vmax = 272 +/- 10 fmol.min-1) was demonstrated at the blood-tissue interface of the choroid plexus. The clearance of DSIP from the ventricles during ventriculo-cisternal perfusion in the rabbit indicated no significant flux of the intact peptide out of the CSF. The results suggest that DSIP crosses the blood-CSF barrier, while the system lacks the specific mechanisms for removal from the CSF found with most, if not all, amino acids and several peptides.

Zlokovic, B.V.; Segal, M.B.; Davson, H.; Jankov, R.M.



Recurrent anaplastic medulloblastoma in cerebrospinal fluid after autologous hematopoietic stem cell transplant.  


Cerebrospinal fluid (CSF) dissemination can be seen relatively frequently in medulloblastomas and its presence at diagnosis is important for determining both treatment and prognosis. The anaplastic variant is an aggressive variant of medulloblastoma with characteristic histopathologic features and unfavorable prognosis that was included in the latest WHO classification. Herein, we report the CSF cytologic features of a case of recurrent anaplastic medulloblastoma in a 17-year-old male patient who had undergone autologous hematopoietic stem cell transplant as a part of the treatment protocol. The malignant cells were large, had high nucleocytoplasmic ratios, and highly pleomorphic, frequently polylobated nuclei with coarse chromatin and 1-3 visible nucleoli. These CSF cytologic features differed significantly from those of classic medulloblastoma, which usually shows small cells with rounded, rather uniform nuclei with fine ("blastic") chromatin. The differential diagnosis of anaplastic medulloblastoma is broader than that of classic medulloblastoma, as it includes metastatic carcinomas and large cell lymphoma, a differential diagnosis especially pertinent in this patient with a history of autologous hematopoietic stem cell transplant. Awareness of these unusual but distinctive cytologic features is important for the accurate diagnosis of anaplastic medulloblastomas in CSF specimens and to avoid possible diagnostic pitfalls. Diagn. Diagn. Cytopathol. 2013;41:980-985. © 2012 Wiley Periodicals, Inc. PMID:22550044

Nelson, Andrew C; Singh, Charanjeet; Brent Clark, H; Pambuccian, Stefan E



Delirium and Cerebrospinal Fluid S100B in Hip Fracture Patients: A Preliminary Study.  


OBJECTIVES: Delirium is associated with an increased risk of long-term cognitive decline, suggesting the possibility of concurrent central nervous system (CNS) injury. S100B is a putative biomarker of CNS injury and elevated serum levels in delirium have been reported. Here we hypothesize that delirium is associated with raised concentrations of cerebrospinal fluid (CSF) S100B. METHODS: Forty-five patients with hip fracture aged over 60 and awaiting surgery under spinal anesthesia were assessed for delirium pre- and post-operatively. CSF S100B levels were measured in samples collected at the onset of surgery. RESULTS: Participants with pre-operative delirium (N = 8) had elevated Log10 CSF S100B (mean: -0.156; SD: 0.238) compared with those without delirium (mean: -0.306; SD: 0.162), Student's t-test t = 2.18, df = 43, p = 0.035. CONCLUSIONS: This study provides preliminary evidence of elevated CSF S100B in current delirium, consistent with findings in serum and with other studies showing elevated S100B in the presence of diverse forms of CNS injury. PMID:23602305

Hall, Roanna J; Ferguson, Karen J; Andrews, Mary; Green, Alison J E; White, Tim O; Armstrong, Ian R; Maclullich, Alasdair M J



Immunocytochemical demonstration of feline infectious peritonitis virus within cerebrospinal fluid macrophages.  


A 4-month-old female entire domestic shorthair cat presented with an acute onset of blindness, tetraparesis and subsequent generalised seizure activity. Haematology and serum biochemistry demonstrated a moderate, poorly regenerative anaemia, hypoalbuminaemia and hyperglobulinaemia with a low albumin:globulin ratio. Serology for feline coronavirus antibody was positive with an elevated alpha-1 acid glycoprotein. Analysis of cisternal cerebrospinal fluid (CSF) demonstrated markedly elevated protein and a mixed, predominately neutrophilic pleocytosis. Immunocytochemistry for feline coronavirus was performed on the CSF with positive staining observed inside macrophages. The cat was subsequently euthanased, and both histopathology and immunohistochemistry were consistent with a diagnosis of feline infectious peritonitis. This is the first reported use of immunocytochemistry for detection of feline coronavirus within CSF macrophages. If this test proves highly specific, as for identification of feline coronavirus within tissue or effusion macrophages, it would be strongly supportive of an ante-mortem diagnosis of feline infectious peritonitis in cats with central nervous system involvement without the need for biopsy. PMID:23744728

Ives, Edward J; Vanhaesebrouck, An E; Cian, Francesco



Cerebrospinal Fluid BACE1 Activity and Brain Amyloid Load in Alzheimer's Disease  

PubMed Central

The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([11C]PIB PET). [11C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [11C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.

Grimmer, Timo; Alexopoulos, Panagiotis; Tsolakidou, Amalia; Guo, Liang-Hao; Henriksen, Gjermund; Yousefi, Behrooz H.; Forstl, Hans; Sorg, Christian; Kurz, Alexander; Drzezga, Alexander; Perneczky, Robert



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


To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of neurological symptoms, and proteomics analysis was performed using nano-LC-Orbitrap mass spectrometry. Additionally, the minocycline concentration in CSF was determined using quantitative matrix-assisted laser desorption/ionization-triple-quadrupole tandem mass spectrometry (MALDI-MS/MS) in the selected reaction monitoring (SRM) mode. Fifty percent of the minocycline-treated EAE animals did not show neurological symptoms on day 14 ("responders"), while the other half displayed neurological symptoms ("nonresponders"), indicating that minocycline delayed disease onset and attenuated disease severity in some, but not all, animals. Neither CSF nor plasma minocycline concentrations correlated with the onset of symptoms or disease severity. Analysis of the proteomics data resulted in a list of 20 differentially abundant proteins between the untreated animals and the responder group of animals. Two of these proteins, complement C3 and carboxypeptidase B2, were validated by quantitative LC-MS/MS in the SRM mode. Differences in the CSF proteome between untreated EAE animals and minocycline-treated responders were similar to the differences between minocycline-treated responders and nonresponders (70% overlap). Six proteins that remained unchanged in the minocycline-treated animals but were elevated in untreated EAE animals may be related to the mechanism of action of minocycline. PMID:22768796

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



Spectrum of total fatty acids in cerebrospinal fluid determined by gas chromatography.  


A simple gas-liquid chromatographic method for the determination of the spectrum of fatty acids in a small volume of cerebrospinal fluid (CSF) is presented. In a group of 49 neurological patients it has been found that in the CSF of the controls (n = 12) there are the following main fatty acids: oleic (27.28%), palmitic (23.23%), stearic (12.21%), linoleic (7.66%), myristic (5.02%), and palmitoleic (4.51%). Altogether 28 fatty acid methyl esters (FAME'S) from 12:0 to 22:2 have been tentatively identified. The majority of them appeared irregularly, sometimes in less than in 10% of cases. The composition of FAME'S in the CSF of patients with lumbar discopathy and with acute ischaemic cerebrovascular accidents does not differ from the control group. A significant difference (P less than 0.01) has been found in the group of hypophyseal adenomas in which the amounts of practically all saturated FAME'S with an odd carbon number are elevated. The same applies to the 18:0 and 20:0 compounds. In the group of atrophic and degenerative CNS processes the palmitic and stearic acids predominated to the detriment of oleic and linoleic acids. PMID:762221

Tichý, J; Skorkovská, I; Base, J