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1

Apolipoproteins in human cerebrospinal fluid.  

PubMed Central

The presence of apolipoproteins A-I, E, C-II, and C-III and the absence of apolipoprotein B was demonstrated in human cerebrospinal fluid. The concentration of apolipoproteins was measured by electroimmunoassay. Apolipoproteins E, C-II, and C-III were present in cerebrospinal fluid at 3--5% of their concentration in plasma; the cerebrospinal fluid level of apolipoprotein A-I was 0.4%. Most of the cerebrospinal fluid apolipoproteins were present in the rho less than 1.21 g/ml lipoprotein fraction. The major apolipoporteins of cerebrospinal fluid are E and A-I. The possible mechanism of transfer and the physiological and pathophysiological role of apolipoproteins in cerebrospinal fluid are postulated. Images

Roheim, P S; Carey, M; Forte, T; Vega, G L

1979-01-01

2

Cerebrospinal Fluid Shunts  

PubMed Central

Cerebrospinal fluid (CSF) shunt technology has undergone rapid advances in the past two decades. As a result, pediatricians and other primary care physicians are being asked with increasing frequency to provide care for persons with CSF shunts. Familiarity with the more common shunts is a prerequisite to intelligent management of shunt related problems. Physicians providing daily care must have carefully documented hospital records and operative notes available to them as well as information detailing the safe evaluation of shunt patency and function if they are to manage patients with CSF shunts properly. In addition, parents and guardians must be alerted to signs and symptoms related to shunt malfunction. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 7.Figure 8.

Sells, Clifford J.; Shurtleff, David B.

1977-01-01

3

Proteomics of Human Cerebrospinal Fluid  

Microsoft Academic Search

Examination of human cerebrospinal fluid (CSF) has been performed for over 100 years. Since CSF is in direct contact with\\u000a the extracellular surface of the brain, the biochemical composition of this fluid is altered in disorders related to the central\\u000a nervous system. Hence, it is of great interest to investigate thoroughly the human CSF proteome, to identify proteins, and\\u000a to

Margareta Ramström; Jonas Bergquist

4

Human cytomegalovirus DNA in cerebrospinal fluid.  

PubMed Central

To determine the involvement of human cytomegalovirus (CMV) in conditions of neurological impairment, detection of CMV DNA was attempted in cerebrospinal fluid obtained from 45 neurologically affected children aged from 1 month to 17 years by means of the polymerase chain reaction. Four patients (congenital CMV encephalopathy with West's syndrome, acute encephalitis, chronic epileptic encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinal fluid. CMV DNA was absent in the cerebrospinal fluid of 11 neurologically unaffected controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis had no CMV DNA in their cerebrospinal fluid. Among the four patients who had CMV DNA in their cerebrospinal fluid, two did not excrete CMV DNA or CMV antigen in the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinal fluid is discussed. By applying the polymerase chain reaction to cerebrospinal fluid, the mode of brain invasion by CMV can be clarified further. Images

Kohyama, J; Kajiwara, M; Shimohira, M; Iwakawa, Y; Okawa, H

1994-01-01

5

Infections in cerebrospinal fluid shunts  

Microsoft Academic Search

Bacterial colonization of cerebrospinal fluid shunts is a cause of significant morbidity, causing not only shunt malfunction\\u000a and chronic ill-health but has also been implicated in an immune-complex glomerulonephritis. Almost all shunt colonizations\\u000a involve Staphylococcus albus which gains access to the shunt during surgery and grows in microcolonies inside the shunt. The\\u000a most reliable means of diagnosis at present is

Prashant Upadhyaya

1985-01-01

6

Cerebrospinal fluid penetration of tigecycline.  

PubMed

We report, in a clinical setting, the tigecycline concentration and area under the concentration-time curve (AUC) - both in blood and in cerebrospinal fluid (CSF) - of a patient with a ventriculo-atrial shunt infection. Tigecycline weakly penetrates CSF the CSF-to-serum concentration ratio was 0.079 and CSF-to-serum AUC(0-12) ratio was 0.067. PMID:24131423

Pallotto, Carlo; Fiorio, Maurizio; D'Avolio, Antonio; Sgrelli, Alessio; Baldelli, Franco; Di Perri, Giovanni; De Socio, Giuseppe Vittorio

2014-01-01

7

Cerebrospinal Fluid Shunt Infections in Children  

Microsoft Academic Search

Infections of cerebrospinal fluid shunts continue to be a substantial source of mortality and morbidity in children with hydrocephalus. Although several therapeutic modalities are currently used for the treatment of shunt infections, there are no clear guidelines for treatment. The purpose of this study was to determine the common pathogens of cerebrospinal fluid shunt infections and evaluate the success of

M. Turgut; D. Alabaz; F. Erbey; E. Kocabas; T. Erman; E. Alhan; N. Aksaray

2005-01-01

8

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.

2012-01-01

9

The maze of the cerebrospinal fluid discovery.  

PubMed

The author analyzes a historical, long, and tortuous way to discover the cerebrospinal fluid. At least 35 physicians and anatomists described in the text have laid the fundamentals of recognition of this biological fluid's presence. On the basis of crucial anatomical, experimental, and clinical works there are four greatest physicians who should be considered as equal cerebrospinal fluid's discoverers: Egyptian Imhotep, Venetian Nicolo Massa, Italian Domenico Felice Cotugno, and French François Magendie. PMID:24396600

Herbowski, Leszek

2013-01-01

10

Cerebrospinal fluid in multiple sclerosis  

PubMed Central

Background: Technological advances have made it possible to examine the human cerebrospinal fluid (CSF) in a manner that was previously impossible. CSF provides a window into the changes that occur in the central nervous system (CNS) in health and disease. Through analysis of the CSF, we discern indirectly the state of health of the CNS, and correctly or incorrectly, draw conclusions regarding mechanisms of CNS injury and repair. Objective, Materials and Methods: To review the current state of knowledge of changes in the CSF in multiple sclerosis. Discussion: Establishing CSF markers that permit evaluation of the various biological processes in multiple sclerosis remains a challenge. Of all the biological processes, inflammatory markers are probably the best identified. Detection of oligoclonal immunoglobulin bands in the CSF is now established as the single most useful laboratory marker in the CSF to aid in the diagnosis of multiple sclerosis. Markers of demyelination, remyelination, neuro-axonal loss, neural repair and regeneration, and astrogliosis are only now being recognized. A good surrogate for any of these pathophysiological processes has not been defined to date. Conclusion: The goal of future research is not only to define surrogate markers in the CSF for each of the above functions, but also to extend it to other more readily accessible body fluids like blood and urine. A synopsis of the current literature in most of these areas of CSF evaluation pertaining to multiple sclerosis is presented in this article.

Rammohan, Kottil W.

2009-01-01

11

Cerebrospinal fluid zinc concentrations in febrile convulsions.  

PubMed Central

Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal fluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinal fluid zinc was tested. Cerebrospinal fluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinal fluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinal fluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinal fluid zinc concentrations.

Garty, B Z; Olomucki, R; Lerman-Sagie, T; Nitzan, M

1995-01-01

12

Cerebrospinal Fluid Pressure and Glaucoma  

PubMed Central

Eyes with normal-pressure glaucoma and those with high-pressure glaucoma can show a similar optic nerve head appearance, while eyes with vascular optic neuropathies show a markedly different optic disc appearance. Factors in addition to intraocular pressure (IOP) may thus play a role in the pathogenesis of glaucomatous optic neuropathy. Clinical and experimental studies showed that (1) physiologic associations between cerebrospinal fluid (CSF) pressure, systemic arterial blood pressure, IOP and body mass index exist; (2) a low CSF pressure was associated with the development of glaucomatous optic nerve damage in cats; (3) patients with normal (intraocular) pressure glaucoma had significantly lower CSF pressure and a higher trans lamina cribrosa pressure difference when compared to normal subjects; and (4) patients with normal- pressure glaucoma as compared with patients with high-pressure glaucoma have a significantly narrower orbital CSF space. A shallow orbital CSF space has been shown to be associated with a low CSF pressure. Due to anatomic reasons, the orbital CSF pressure and the optic nerve tissue pressure (and not the atmospheric pressure) form the retro-laminar counter-pressure against the IOP and are thus part of the trans-lamina cribrosa pressure difference and gradient. Assuming that an elevated trans-lamina cribrosa pressure difference and a steeper trans-lamina cribrosa pressure gradient are important for glaucomatous optic nerve damage, a low orbital CSF pressure would therefore play a role in the pathogenesis of normal-(intraocular) pressure glaucoma. Due to the association between CSF pressure and blood pressure, a low blood pressure could be indirectly involved.

Jonas, Jost B.; Wang, Ningli

2013-01-01

13

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.

2012-01-01

14

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

2001-01-01

15

Extracranial repair of cerebrospinal fluid otorhinorrhea  

Microsoft Academic Search

Forty-eight patients with cerebrospinal fluid leaks comprise this retrospective study. There were 39 traumatic and 9 spontaneous leaks. Nine patients were initially managed with bed rest and spinal drainage, but 3 patients in this group ultimately required surgical intervention for repair of their persistent leaks. Thirty-nine patients had surgery as initial therapy, with 33 extracranial repairs, 2 intracranial repairs, and

Mark S. Persky; Stephen G. Rothstein; Stephen D. Breda; Noel L. Cohen; Paul Cooper; Joseph Ransohoff

1991-01-01

16

Assessment of cerebrospinal fluid outflow resistance  

Microsoft Academic Search

The brain and the spinal cord are contained in a cavity and are surrounded by cerebrospinal fluid (CSF), which provides physical\\u000a support for the brain and a cushion against external pressure. Hydrocephalus is a disease, associated with disturbances in\\u000a the CSF dynamics, which can be surgically treated by inserting a shunt or third ventriculostomy. This review describes the\\u000a physiological background,

Anders Eklund; Peter Smielewski; Iain Chambers; Noam Alperin; Jan Malm; Marek Czosnyka; Anthony Marmarou

2007-01-01

17

Cerebrospinal fluid secretion by the choroid plexus.  

PubMed

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

2013-10-01

18

A Case of Cerebrospinal Fluid Rhinorrhoea: A Surgical Challenge  

PubMed Central

CEREBROSPINAL FLUID rhinorrhoea is defined as the leakage of CEREBROSPINAL FLUID through the nose due to communication between nasal cavity and Sub-arachnoid space. It occurs due to breach in 4 layers – mucosa of the nose and PNS, skull base, Duramater, Subarachnoid membrane. With the advent of nasal endoscope and advancement in technology, Endoscopic Endonasal closure of CEREBROSPINAL FLUID leak has reached tremendous heights due to exact localization and precise placement of graft. In this article, we are publishing a case report of Non-traumatic normal pressure CEREBROSPINAL FLUID leak of more than 1.5cm in size which was successfully closed Endoscopically by multilayered technique

R, Sumitha; Hari, P M; Kumar, S Ramya; Hariprasad, R

2013-01-01

19

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

1981-01-01

20

Pseudoepiphora from cerebrospinal fluid leak: case report.  

PubMed Central

A 4-year-old tearing child with obstruction of the nasolacrimal duct was treated with dacryocystorhinostomy three years after naso-orbital injury. However, what appeared to be tearing persisted, and meningitis developed. Coronal CT scans demonstrated traumatic encephalocele of the posterior superior orbital roof. A chronic orbital cerebrospinal fluid (CSF) leak was diagnosed. To our knowledge no case of chronic CSF leak has been reported that simulated tearing in an otherwise asymptomatic child. In the tearing patient who has a naso-orbital fracture the possibility of chronic CSF leak should be considered. Images

Dryden, R M; Wulc, A E

1986-01-01

21

Novel Cyclovirus in Human Cerebrospinal Fluid, Malawi, 2010-2011  

PubMed Central

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.

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

2013-01-01

22

Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders  

PubMed Central

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

Constantinescu, Radu; Mondello, Stefania

2013-01-01

23

A new look at cerebrospinal fluid circulation  

PubMed Central

According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation.

2014-01-01

24

Proteomic analysis of multiple sclerosis cerebrospinal fluid.  

PubMed

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

2004-06-01

25

Cerebrospinal fluid leak of the fallopian canal.  

PubMed

Spontaneous cerebrospinal fluid (CSF) leaks from the fallopian canal are extremely rare, as only a few cases have been reported in the world literature. We describe a case of spontaneous CSF otorrhea through an enlarged geniculate fallopian canal. The patient was a 45-year-old woman who presented with a history of CSF rhinorrhea and otorrhea from the right ear. Myringotomy and tube insertion revealed CSF otorrhea. Contrast-enhanced computed tomography revealed that the geniculate fossa was smoothly enlarged (demonstrating remodeling of bone). A middle fossa craniotomy with temporal bone exploration was performed. Intraoperative inspection detected the presence of a fistula secondary to a lateral extension of the subarachnoid space through the labyrinthine segments of the fallopian canal. We discuss the management of this unusual finding, which involves sealing the fistula while preserving facial nerve function. PMID:23532657

Teufert, Karen B; Slattery, William H

2013-03-01

26

Imhotep and the discovery of cerebrospinal fluid.  

PubMed

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

Blomstedt, Patric

2014-01-01

27

beta-Endorphin in human cerebrospinal fluid.  

PubMed

beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary. PMID:78323

Jeffcoate, W J; Rees, L H; McLoughlin, L; Ratter, S J; Hope, J; Lowry, P J; Besser, G M

1978-07-15

28

Case report. Isolation of Cladosporium cladosporioides from cerebrospinal fluid.  

PubMed

Cladosporium cladosporioides was isolated from three subsequent cerebrospinal fluid specimens and from a brain biopsy specimen of a human patient. Susceptibility testing of the isolate was performed against seven antifungal agents. PMID:12472729

Kantarcioglu, A S; Yücel, A; de Hoog, G S

2002-12-01

29

Fluids and Barriers of the CNS: a new journal encompassing Cerebrospinal Fluid Research  

PubMed Central

This article celebrates the re-launch of Cerebrospinal Fluid Research in its new format as Fluids and Barriers of the CNS. Editors-in Chief, Hazel Jones and Tetsuya Terasaki, anticipate that this expanded journal will provide a unique and specialist platform for the publication of research in cerebrospinal fluid and all brain barriers and fluid systems in both health and disease.

2011-01-01

30

Ouabain-like activity in human cerebrospinal fluid.  

PubMed Central

Human cerebrospinal fluid has been found to mimic the effect of ouabain on net Na+ efflux and 86Rb+ influx across erythrocyte membranes and on the in vitro activity of a purified Na+/K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) derived from canine kidney. These results indicate the possible existence in human cerebrospinal fluid of an endogenous factor with ouabain-like activity, which might be linked to sodium metabolism.

Halperin, J; Schaeffer, R; Galvez, L; Malave, S

1983-01-01

31

Vitamin E (tocopherols) in human cerebrospinal fluid.  

PubMed

Cerebrospinal fluid (CSF) and blood were obtained at the time of myelographic examinations from 40 adult, male, human subjects with no neurologic or metabolic abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid chromatography. In subjects with normal concentrations of CSF protein (n = 22), the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD) and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6 mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF correlated significantly (P less than 0.001) with both total protein and albumin concentrations, suggesting that tocopherol transport into CSF is linked with that of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable induction (lag) period. This is due to the presence of other antioxidants in human CSF. PMID:1984352

Vatassery, G T; Nelson, M J; Maletta, G J; Kuskowski, M A

1991-01-01

32

Molecular Mechanisms of Cerebrospinal Fluid Production  

PubMed Central

The epithelial cells of the choroid plexuses secrete cerebrospinal fluid (CSF), by a process which involves the transport of Na+, Cl- and HCO3- from the blood to the ventricles of the brain. The unidirectional transport of ions is achieved due to the polarity of the epithelium, i.e. the ion transport proteins in the blood-facing (basolateral) membrane are different to those in the ventricular (apical) membrane. The movement of ions creates an osmotic gradient which drives the secretion of H2 O. A variety of methods (e.g. isotope flux studies, electrophysiological, RT-PCR, in situ hybridization and immunocytochemistry) have been used to determine the expression of ion transporters and channels in the choroid plexus epithelium. Most of these transporters have now been localized to specific membranes. For example, Na+-K+ ATPase, K+ channels and Na+-2Cl--K+ cotransporters are expressed in the apical membrane. By contrast the basolateral membrane contains Cl--HCO3 exchangers, a variety of Na+ coupled HCO3- transporters and K+-Cl- cotransporters. Aquaporin 1 mediates water transport at the apical membrane, but the route across the basolateral membrane is unknown. A model of CSF secretion by the mammalian choroid plexus is proposed which accommodates these proteins. The model also explains the mechanisms by which K+ is transported from the CSF to the blood.

BROWN, P. D.; DAVIES, S. L.; SPEAKE, T.; MILLAR, I. D.

2006-01-01

33

Cerebrospinal fluid gusher in cochlear implantation.  

PubMed

Objectives To share our experience of cerebrospinal fluid (CSF) gusher in cochlear implantation. Methods Demographic, radiological, and surgical results of patients with CSF gusher in 523 consecutive cochlear implant recipients including children and adults as well as our management technique were evaluated and a review of the literature has been included. Results Fifteen (2.87%) cases had CSF gusher. Two patients (13.3%) were adults with post-lingual hearing loss and the rest 12 (86.7%) were children with congenital hearing loss. Twelve patients (80%) had various types of inner ear malformation. Three patients (20%) had no predictable risk of CSF gusher from history or pre-operative imaging. In all patients, CSF gushers were controlled with our technique of packing the electrode entrance site with no additional measures. Conclusion CSF gusher may occur with post-lingual hearing loss and in children with apparently unremarkable imaging and history. Thus, surgeons should always be ready to manage it. Management of CSF gusher can be mainly performed during the initial surgery by precise tight packing of the electrode entrance site. Furthermore, non-surgical or surgical measures are rarely required to stop a persistent leak. Our results show that our management technique may be recommended as well. PMID:24660749

Eftekharian, Ali; Amizadeh, Maryam

2014-05-01

34

Meningitis in Preterm Neonates: Importance of Cerebrospinal Fluid Parameters  

PubMed Central

Objective: Cerebrospinal fluid parameters are of great importance in diagnosing meningitis, but normal values for preterm neonates are based on small, single-center studies. We sought to determine current values for preterm neonate cerebrospinal fluid parameters and assess the association of cerebrospinal fluid parameters with culture proven meningitis. Study Design: Cohort study of the first lumbar puncture from 4,632 neonates <34 weeks gestation performed in the years 1997-2004 at 150 neonatal intensive care units managed by the Pediatrix Medical Group. Results: We identified 95 cases of meningitis from the 4,632 lumbar punctures. The area under the receiver operating characteristic curves for white blood cell count, glucose, and protein were 0.80, 0.63, and 0.72 respectively for prediction of culture proven meningitis. Conclusion: Cerebrospinal fluid parameters used to diagnose meningitis in the absence of dependable cerebrospinal fluid cultures are unreliable. Caution should be employed when interpreting cerebrospinal fluid parameters in the premature neonate.

Smith, P. Brian; Garges, Harmony P.; Cotten, C. Michael; Walsh, Thomas J.; Clark, Reese H.; Benjamin, Daniel K.

2009-01-01

35

[Diagnosis of spinal diseases by cerebrospinal fluid examination].  

PubMed

In this work, changes in the cerebrospinal fluid in acute and chronic polyneuritis as well as in the Guillan-Barré-Strohl syndrome are discussed and and it is pointed out that a specific coordination of the inflammatory cerebrospinal fluid syndromes to certain pathogens or noxae cannot be made. For the differentiation of the Guillain-Barré-Strohl syndrome and existence of increased gamma-globulin bands with identical mobility in the serum is pointed out. In myelitic disease pictures, acute and chronic cerebrospinal fluid syndromes are distinguished also in the cerebrospinal fluid according to the clinical course; regular changes, however, cannot be derived. Syphilitic cerebrospinal-fluid syndromes can easily be differentiated by their immunoactive findings. In multiple sclerosis, we distinguish between typical and atypical changes in the cerebrospinal fluid. Above all, the oligoclonal bands, i. e. the discontinuous proceeding of the gamma-globulin zone and the existence of several bands in the agar gel electrophoresis, play an essential role. In 95 per cent of the cases, oligoclonal bands can be shown. There are no greater differences with respect to oligoclonal bands between intermittent and chronic-progressive courses. For the differential diagnosis of haemorrhagic syndromes, the cerebrospinal fluid cell picture can make a considerable contribution. Macrophages loaded with erythrocytes indicate that a haemorrhage occurred 12 to 18 hours before; macrophages loaded with haemosiderin indicate a haemorrhage that occurred 6 to 8 days before; and macrophages loaded with erythrocytes and haemosiderin indicate a seeping haemorrhage or an event that occurred several times. The Nonne-Froin syndrome indicates a massive protein increase often with a regular or only slightly increased number of cells. The importance of the Queckenstedt tests is pointed out. A particular role is played by meningitis carcinomatosa et sarcomatosa with the demonstration of a great number of tumour cells. PMID:532463

Schmidt, R M

1979-01-01

36

Cerebrospinal Fluid Amyloid ?40 Is Decreased in Cerebral Amyloid Angiopathy  

PubMed Central

Cerebral amyloid angiopathy is caused by deposition of the amyloid ? protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid ?40 and ?42 proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid ?40 (p < 0.01 vs controls or Alzheimer disease) and amyloid ?42 concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid ?42 and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid ?40 as well as amyloid ?42 protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid ? proteins toward the cerebrospinal fluid.

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

2013-01-01

37

Counting cells in cerebrospinal fluid collected directly on membrane filters  

PubMed Central

Accurate enumeration of cells in the cerebrospinal fluid is not feasible with the current method of counting cells in the Fuchs Rosenthal or Neubauer chamber when the count is near normal since the volume of fluid examined is too small. A sample of adequate volume to permit such accurate assessment may be collected from the lumbar puncture needle into a syringe through a ruled membrane filter in a Swinney cartridge. A study of 291 samples shows that the upper limit of the normal cerebrospinal fluid count is 2000 cells/ml (2/cmm) and not 5000/ml (5/cmm) as is currently accepted. Images

Burechailo, F.; Cunningham, T. A.

1974-01-01

38

Cerebrospinal fluid oligoclonal bands in childhood opsoclonus-myoclonus.  

PubMed

Oligoclonal bands in cerebrospinal fluid reflect local B-cell responses associated with various neuroinflammatory disorders. In opsoclonus-myoclonus syndrome, cerebrospinal fluid B-cell expansion was demonstrated, but no studies of oligoclonal bands are available. In a prospective case-control study of 132 children (103 with opsoclonus-myoclonus, 29 neurologic control subjects), cerebrospinal fluid oligoclonal bands, measured by isoelectric focusing with immunofixation, were observed in 35% with opsoclonus-myoclonus and none of the control subjects, with the highest frequency in severe cases (56%). In oligoclonal band-positive patients, the mean band number was 5 ± 3 S.D. (range, 2-10) and the total severity score was significantly higher than in band-negative patients, whereas the frequency of CD19(+) B cells, opsoclonus-myoclonus duration, neuroblastoma detection, and relapse history did not differ. The cerebrospinal fluid immunoglobulin G synthesis rate, immunoglobulin index, and Q albumin were normal. In 17 untreated children receiving adrenocorticotropic hormone, intravenous immunoglobulins, and rituximab, the number of oligoclonal band-positive decreased by 75%, and the mean band count fell by 80%. Oligoclonal band detection adds useful information to neuroimmunologic "staging" in opsoclonus-myoclonus. However, flow cytometry provides a more sensitive measure of B-cell infiltration. Cerebrospinal fluid oligoclonal bands warrant monitoring in long-term follow-up studies of disease-modifying drugs for opsoclonus-myoclonus. PMID:21723456

Pranzatelli, Michael R; Slev, Patricia R; Tate, Elizabeth D; Travelstead, Anna L; Colliver, Jerry A; Joseph, Suja Anne

2011-07-01

39

Characterization of Transferrin Glycopeptide Structures in Human Cerebrospinal Fluid  

PubMed Central

Transferrin in cerebrospinal fluid (CSF) exists as a mixture of silao and asialo glycoforms believed to originate from liver and brain respectively. We have previously shown that alteration in the asialo glycoform pattern could be an indication of certain anomalies in the central nervous system. Additionally, CSF asialo-transferrin has been shown to be a reliable marker to assess cerebrospinal leakage in head trauma. Therefore, the CSF transferrin glycoform pattern could be a useful diagnostic and prognostic tool. In this study we sought to characterize, in-depth, the transferrin glycovariants in cerebrospinal fluid using a combination of two-dimensional gel electrophoresis and high precision mass spectrometry analysis. Cerebrospinal fluid transferrin was detected as multiple spots (seven major spots) with different isoelectric points and slight shift in apparent molecular mass. High resolution (>60,000) and high accuracy (< 3 ppm error) mass spectrometry analysis revealed that each spot had a unique glycopeptide signature. MSn analysis enabled characterization of the glycan structure directly from the in-gel digested spots. The multiple spots detected for cerebrospinal fluid transferrin were mainly due to heterogeneity of di-antennary and tri-antennary glycans harboring a varying number of terminal N-acetylneuraminic acids and the existence of a high mannose and high N-acetylhexosamine glycosylated species.

Brown, Kristy J.; Vanderver, Adeline; Hoffman, Eric P.; Schiffmann, Raphael; Hathout, Yetrib

2011-01-01

40

Characterization of Transferrin Glycopeptide Structures in Human Cerebrospinal Fluid.  

PubMed

Transferrin in cerebrospinal fluid (CSF) exists as a mixture of silao and asialo glycoforms believed to originate from liver and brain respectively. We have previously shown that alteration in the asialo glycoform pattern could be an indication of certain anomalies in the central nervous system. Additionally, CSF asialo-transferrin has been shown to be a reliable marker to assess cerebrospinal leakage in head trauma. Therefore, the CSF transferrin glycoform pattern could be a useful diagnostic and prognostic tool. In this study we sought to characterize, in-depth, the transferrin glycovariants in cerebrospinal fluid using a combination of two-dimensional gel electrophoresis and high precision mass spectrometry analysis. Cerebrospinal fluid transferrin was detected as multiple spots (seven major spots) with different isoelectric points and slight shift in apparent molecular mass. High resolution (>60,000) and high accuracy (< 3 ppm error) mass spectrometry analysis revealed that each spot had a unique glycopeptide signature. MS(n) analysis enabled characterization of the glycan structure directly from the in-gel digested spots. The multiple spots detected for cerebrospinal fluid transferrin were mainly due to heterogeneity of di-antennary and tri-antennary glycans harboring a varying number of terminal N-acetylneuraminic acids and the existence of a high mannose and high N-acetylhexosamine glycosylated species. PMID:22408387

Brown, Kristy J; Vanderver, Adeline; Hoffman, Eric P; Schiffmann, Raphael; Hathout, Yetrib

2012-02-15

41

Cerebrospinal fluid hepatocyte growth factor level in meningitis  

Microsoft Academic Search

Background and Purpose: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis. Methods: In a retrospective study, the levels of HGF in the cerebrospinal fluid of 65 patients were measured prior to treatment.

Cheng-Len Sy; Hung-Chin Tsai; Shue-Ren Wann; Susan Shin-Jung Lee; Yung-Ching Liu; Yao-Shen Chen

2008-01-01

42

Cerebrospinal fluid GABA levels in various neurological and psychiatric diseases.  

PubMed Central

Cerebrospinal fluid gamma-aminobutyric acid (CSF-GABA) was analysed by radioreceptor assay in 16 normal controls and 84 patients with various neurological and psychiatric diseases. In patients with spinocerebellar degeneration, neuro-Behçet's syndrome and Parkinson's disease, CSF-GABA levels were decreased. On the other hand, increased CSF-GABA levels were detected in patients with meningitis.

Kuroda, H; Ogawa, N; Yamawaki, Y; Nukina, I; Ofuji, T; Yamamoto, M; Otsuki, S

1982-01-01

43

Transnasal endoscopic treatment of cerebrospinal fluid leak: 17 years' experience  

PubMed Central

Summary Aim of this report is to describe the long-term results of endoscopic endonasal repair of cerebrospinal fluid leak using a septal mucoperichondrial graft. A case series of 52 patients operated for cerebrospinal fluid rhinorrhea between 1990 and 2006 is presented. All patients underwent surgical treatment for endoscopic endonasal closure of a cerebrospinal fluid leak using a septal mucoperichondrial graft. No lumbar drain and fluorescein tests were used. The intra-operative localization of the fistula was aided by Valsalva’s manoeuvre by the anaesthetist. The success rate, after the first attempt, was 88.5% (46/52 patients); for the remaining 11.5% (6/52 patients), a second attempt was necessary which proved successful in 5 cases, raising the overall success rate to 98.1% (51/52 patients). Relapse occurred in only one case (1.9%), after the second attempt. In conclusion, a free mucoperichondrial graft offered good results for cerebrospinal fluid leak repair. In the Authors’ experience, a high success rate can be achieved without the use of intrathecal fluorescein and lumbar drain.

Presutti, L; Mattioli, F; Villari, D; Marchioni, D; Alicandri-Ciufelli, M

2009-01-01

44

Cerebrospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis  

Microsoft Academic Search

Objectives: cerebrospinal fluid (CSF) levels of interleukin (IL)-1 ? and tumor necrosis factor (TNF) a were measured to assess the effect and application of dexamethasone (Dex) therapy for bacterial meningitis.Methods: associations between clinical findings and CSF parameters were first investigated, and prognosis was compared between 25 patients with Dex and 12 without Dex therapy.Results: patients with the presence of disturbed

Shouichi Ohga; Kenji Okada; Kohji Ueda; Hidetoshi Takada; Mitsuhiro Ohta; Tomonobu Aoki; Naoko Kinukawa; Sumio Miyazaki; Toshiro Hara

1999-01-01

45

Cerebrospinal fluid findings in Devic’s neuromyelitis optica  

Microsoft Academic Search

Relapsing Devic’s neuromyelitis optica (DNO) may be clinically undistinguishable from multiple sclerosis (MS), thus the differential diagnosis relies mainly on neuroimaging and cerebrospinal fluid (CSF) findings. We studied CSF samples from 44 patients with DNO submitted to at least one lumbar puncture. Pleocytosis, IgG synthesis and blood brain barrier damage were the most frequent abnormalities, pleocytosis being very suggestive of

M. Zaffaroni

2004-01-01

46

Serum and Cerebrospinal Fluid Concentrations of Linezolid in Neurosurgical Patients  

Microsoft Academic Search

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid

Pavlos Myrianthefs; Sophia L. Markantonis; Konstantinos Vlachos; Maria Anagnostaki; Eleni Boutzouka; Dimitris Panidis; Georgios Baltopoulos

2006-01-01

47

Cerebrospinal Fluid Nitrate Levels in Patients with Multiple Sclerosis  

Microsoft Academic Search

It has been suggested that nitric oxide (NO) could be implicated in the pathogenesis of multiple sclerosis (MS). Recently, two groups reported increased cerebrospinal fluid (CSF) nitrate levels (oxidation product that provides an indirect estimation of NO) in MS patients. However, another group did not confirm these findings. We studied the CSF and plasma levels of nitrate with a kinetic

Fernando de Bustos; José Antonio Navarro; Clara de Andrés; José Antonio Molina; Félix Javier Jiménez-Jiménez; Miguel Ortí-Pareja; Teresa Gasalla; Antonio Tallón-Barranco; Antonio Martínez-Salio; Joaquín Arenas

1999-01-01

48

Repair of traumatic cerebrospinal fluid leaks using tissue adhesives.  

PubMed

14 cases of post-traumatic cerebrospinal fluid leaks, sealed with tissue adhesives and fascia, or galea, are reported. None of the patients had recurrence in a follow-up ranging from five months to three years. Tissue adhesives provided a tough adhesion of the patch and, as a consequence, an immediate and stable repair of the leak. PMID:1223246

Rocca, A; Turtas, S

1975-01-01

49

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

PubMed Central

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

2010-01-01

50

A new look at cerebrospinal fluid movement  

PubMed Central

Brinker et al. extensively reviewed recent findings about CSF circulation in a recent article: “A new look at cerebrospinal circulation”, but did not analyze some important available data in sufficient detail. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. These are based on: a) physiological oscillations of arterial and venous blood during cranio-spinal blood circulation; b) respiratory activity, and c) body activity and posture. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. It seems that efflux transport systems at capillary endothelium may be more important for brain homeostasis than the removal of metabolites by CSF flow. Thus, when discussing the CSF dynamics we suggest that a more appropriate term would be CSF movement rather than CSF circulation.

2014-01-01

51

Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer's disease  

PubMed Central

Dementia due to Alzheimer’s disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current AD clinical diagnosis, biomarkers of AD pathologies are currently being sought. Reductions in cerebrospinal fluid levels of ?-amyloid 42 (a marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are well-established as biomarkers useful for AD diagnosis and prognosis. However, novel markers for other features of AD pathophysiology (e.g., ?-amyloid processing, neuroinflammation and neuronal stress/dysfunction) and for other non-AD dementias are required to improve the accuracy of AD disease diagnosis, prognosis, staging and therapeutic monitoring (theragnosis). This article discusses the potential of several promising novel cerebrospinal fluid analytes, highlights the next steps critical for advancement in the field, and provides a prediction on how the field may evolve in 5–10 years.

Fagan, Anne M; Perrin, Richard J

2012-01-01

52

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

1990-01-01

53

Liquid chromatographic assay of dityrosine in human cerebrospinal fluid  

Microsoft Academic Search

A micro-scale method for separation and measurement of dityrosine in human cerebrospinal fluid (CSF) is described utilizing liquid-liquid extraction and ion-paired, reversed-phase high-performance liquid chromatography with fluorimetric detection. A mobile phase containing 1-heptanesulfonic acid linearly increased in methanol from 0 to 100% over 30 min allows the resolution of dityrosine from other fluorescent compounds with excitation at 285 nm and

Maged Abdelrahim; Elena Morris; Jeannean Carver; Stephen Facchina; Alison White; Ajay Verma

1997-01-01

54

Identification and determination of succinyladenosine in human cerebrospinal fluid  

Microsoft Academic Search

Succinyladenosine (S-Ado) is a biochemical marker of adenylosuccinase deficiency – the genetic defect of purine de novo synthesis. S-Ado has been previously reported as normally undetectable in cerebrospinal fluid (CSF) of children not suffering from this defect. In present study, we employed solid-phase extraction and thin-layer chromatography for isolation of a compound with spectral and chromatographic characteristics identical to S-Ado

Jakub Krijt; Stanislav Kmoch; Hana Hartmannová; Vladim??r Havl???ek; Ivan Šebesta

1999-01-01

55

Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases  

Microsoft Academic Search

In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases\\u000a and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However,\\u000a large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define\\u000a a normal reference spectrum of routine

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

2011-01-01

56

HPLC method for measurementof purine nucleotidedegradationproductsin cerebrospinal fluid  

Microsoft Academic Search

We describe a convenient method for the separation and quantification of xanthine, hypoxanthine, and uric acid in 20 .tL of cerebrospinal fluid (CSF) with use of HPLC and ultraviolet detection. The analysis is performed on a Sepha- ron SGX C18 column and the elution system consists of potassium phosphate buffer, pH 5.1, with 20 mL\\/L metha- nol. The lower limit

LUBOMIR KURAKA; BRANISLAV LIA

57

Volume distribution of cerebrospinal fluid using multispectral MR imaging  

Microsoft Academic Search

The goal of this study was to design a reliable method to quantify and visualize the anatomical distribution of cerebrospinal fluid (CSF) intracranially. The method should be clinically applicable and based on multispectral analysis of three-dimensional (3D) magnetic resonance images. T1-weighted, T2-weighted and proton density-weighted fast 3D gradient pulse sequences were used to form high resolution multispectral 3D images of

Arvid Lundervold; Torfinn Taxt; Lars Ersland; Anne Marie Fenstad

2000-01-01

58

Regional specificity of cerebrospinal fluid abnormalities in first episode schizophrenia  

Microsoft Academic Search

The timing and regional specificity of cerebrospinal fluid (CSF) enlargements have not been well described in schizophrenia. High-resolution magnetic resonance images and computational image analysis methods were used to localize cross-sectional changes in lateral ventricle and sulcal and subarachnoid CSF in first episode schizophrenia patients (51 males\\/21 females) and healthy subjects (37 males\\/41 females). Volumes were obtained for each lateral

Katherine L. Narr; Robert M. Bilder; Roger P. Woods; Paul M. Thompson; Philip Szeszko; Delbert Robinson; Martina Ballmaier; Bradley Messenger; YungPing Wang; Arthur W. Toga

2006-01-01

59

Alzheimer's disease: paired helical filament immunoreactivity in cerebrospinal fluid  

Microsoft Academic Search

A competitive enzyme-linked immunosorbent assay with high sensitivity has been developed for measuring ubiquitin reactivity of paired helical filaments (PHF). Using the assay, ubiquitin immunoreactivity was estimated in the cerebrospinal fluid (CSF) of 44 patients who had been clinically diagnosed as having Alzheimer's disease (AD) and of 38 control patients, including 20 neurological cases. Monoclonal antibody (mAb) 5–25 to isolated

G. P. Wang; K. Iqbal; G. Bucht; B. Winblad; H. M. Wisniewski; I. Grundke-Iqbal

1991-01-01

60

Cisternal cerebrospinal fluid analysis in 24 sheep with chronic coenurosis.  

PubMed

Coenurosis, a neurological parasitic infection of ruminants caused by the larval stage of Taenia multiceps, is commonly reported in Sardinia, the most representative region for ovine population in Italy. Chronic form appears as a consequence of cyst development, frequently reported in the brain and spinal cord. Diagnostic suspect of coenurosis is based on physical and neurological examination. The aim of this article is to describe physical, biochemical and cytological aspects of cisternal cerebrospinal fluid of 24 sheep with chronic coenurosis and to evaluate whether these alterations are helpful in the diagnosis of coenurosis. Cerebrospinal fluid was altered in 20 animals (83.3%). Increase of total protein was revealed in 7 animals (29.2%); an increase of total nucleated cell count was observed in 18 samples (75%). Cytological examination revealed mononuclear pleocytosis in 17 animals (70.1%). Eosinophils were observed in 16 animals in various degree (66.7%). Our results show that cerebrospinal fluid confirms signs of Central Nervous System inflammation in 20 animals out of 24 (83.3%) and in particular it was useful to identify a parasitic inflammation in 66.7% of the animals in which eosinophils were observed. Considering the results of this study, the very absence of significant neutrophilic pleocytosis could be considered useful to diagnose chronic cerebral coenurosis. PMID:24715594

Zobba, Rosanna; Manunta, Maria Lucia; Evangelisti, Maria Antonietta; Alberti, Alberto; Visco, Stefanoa; Dimauro, Corrado; Pinna Parpaglia, Maria Luisa

2014-03-31

61

Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma*  

PubMed Central

Cerebrospinal fluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinal fluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the identification of biomarkers and classification of neurological diseases.

Locasale, Jason W.; Melman, Tamar; Song, Susan; Yang, Xuemei; Swanson, Kenneth D.; Cantley, Lewis C.; Wong, Eric T.; Asara, John M.

2012-01-01

62

Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test.  

PubMed

Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid ?-42 (A?-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer's disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers A?-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF A?-42 correlated with poor cognitive performance (r=0.687, p<0.001 for Korean Mini Mental State Examination; r=0.568, p=0.001 for Frontal Assessment Battery; r=-0.439, p=0.014 for iNPH grading scale [iNPHGS] cognitive score; r=-0.588, p=0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r=-0.624, p<0.001 for Timed Up and Go Test; r=-0.652, p<0.001 for 10meter walking test; r=-0.578, p=0.001 for Gait Status Scale; r=-0.543, p=0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/A?-42 ratios were significantly higher in CSFTT non-responders compared to responders (p=0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses. PMID:24836892

Kang, Kyunghun; Ko, Pan-Woo; Jin, Myungwon; Suk, Kyoungho; Lee, Ho-Won

2014-08-01

63

Quantitative proteomics comparison of arachnoid cyst fluid and cerebrospinal fluid collected perioperatively from arachnoid cyst patients  

PubMed Central

Background There is little knowledge concerning the content and the mechanisms of filling of arachnoid cysts. The aim of this study was to compare the protein content of arachnoid cysts and cerebrospinal fluid by quantitative proteomics to increase the understanding of arachnoid cysts. Methods Arachnoid cyst fluid and cerebrospinal fluid from five patients were analyzed by quantitative proteomics in two separate experiments. In a label-free experiment arachnoid cyst fluid and cerebrospinal fluid samples from individual patients were trypsin digested and analyzed by Orbitrap mass spectrometry in a label-free manner followed by data analysis using the Progenesis software. In the second proteomics experiment, a patient sample pooling strategy was followed by MARS-14 immunodepletion of high abundant proteins, trypsin digestion, iTRAQ labelling, and peptide separation by mix-phase chromatography followed by Orbitrap mass spectrometry analysis. The results from these analyzes were compared to previously published mRNA microarray data obtained from arachnoid membranes. Results We quantified 348 proteins by the label-free individual patient approach and 1425 proteins in the iTRAQ experiment using a pool from five patients of arachnoid cyst fluid and cerebrospinal fluid. This is by far the largest number of arachnoid cyst fluid proteins ever identified, and the first large-scale quantitative comparison between the protein content of arachnoid cyst fluid and cerebrospinal fluid from the same patients at the same time. Consistently in both experiment, we found 22 proteins with significantly increased abundance in arachnoid cysts compared to cerebrospinal fluid and 24 proteins with significantly decreased abundance. We did not observe any molecular weight gradient over the arachnoid cyst membrane. Of the 46 proteins we identified as differentially abundant in our study, 45 were also detected from the mRNA expression level study. None of them were previously reported as differentially expressed. We did not quantify any of the proteins corresponding to gene products from the ten genes previously reported as differentially abundant between arachnoid cysts and control arachnoid membranes. Conclusions From our experiments, the protein content of arachnoid cyst fluid and cerebrospinal fluid appears to be similar. There were, however, proteins that were significantly differentially abundant between arachnoid cyst fluid and cerebrospinal fluid. This could reflect the possibility that these proteins are affected by the filling mechanism of arachnoid cysts or are shed from the membranes into arachnoid cyst fluid. Our results do not support the proposed filling mechanisms of oncotic pressure or valves.

2013-01-01

64

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.

2012-01-01

65

Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase  

PubMed Central

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

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

2001-01-01

66

Cervical intradural disc herniation and cerebrospinal fluid leak.  

PubMed

Cervical intradural disc herniation (IDH) is a rare condition and only 25 cases of cervical have been reported. We report a 45-year-old male who presented with sudden onset right lower limb weakness after lifting heavy weight. Magnetic resonance imaging of the cervical spine showed C5/6 disc prolapse with intradural extension. The patient underwent C5/6 discectomy through anterior cervical approach. Postoperatively, the patient improved in stiffness but developed cerebrospinal fluid leak and the leak resolved with multiple lumbar punctures. PMID:21743181

Kansal, Ritesh; Mahore, Amit; Kukreja, Sanjay

2011-01-01

67

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

PubMed

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

2012-08-01

68

Blood-Cerebrospinal Fluid Barrier Permeability in Alzheimer's Disease1  

PubMed Central

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

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

2011-01-01

69

Cerebrospinal fluid pressure in conscious head-down tilted rats  

NASA Technical Reports Server (NTRS)

The acute effects of a 1-h -45 deg head-down tilt on continouously recorded cerebrospinal fluid pressure (PCSF) of conscious rats are studied in order to investigate the shift of blood volume into the thoracic cavity in microgravity. PCSF, evaluated in 15-min time blocks over a 3-h experiment, increased slightly (less than 0.05) during the first 30 min of a control hour at 0 deg. There was a transient increase for about 5 min immediately after tilt (-45 deg) that may have been due to head movement after the position change. PCSF was statistically unchanged (above 0.05) during the second (-45 deg) hour and the third (0 deg) recovery hour. It is shown that the dynamics of intracranial pressure regulation can accommodate the acute cephalad fluid shift after tilting.

Severs, Walter B.; Morrow, Bret A.; Keil, Lanny C.

1991-01-01

70

Cerebrospinal fluid pressure in conscious head-down tilted rats.  

PubMed

Cerebrospinal fluid pressure (PCSF) was continuously measured in conscious male Sprague-Dawley rats gently restrained by a cotton towel. PCSF, evaluated in 15-min time blocks over a 3-h experiment, increased slightly (p less than 0.05) during the first 30 min of a control hour at 0 degree. There was a transient increase for about 5 min immediately after tilt (-45 degrees) that may have been due to head movement after the position change. However, PCSF was statistically unchanged (p greater than 0.05) during the 2nd (-45 degrees) hour and the 3rd (0 degree) recovery hour. The data show that the dynamics of intracranial pressure regulation can accommodate the acute cephalad fluid shift after tilting. PMID:1764005

Severs, W B; Morrow, B A; Keil, L C

1991-10-01

71

Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy  

Microsoft Academic Search

Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease)

M. M. Verbeek; H. P. H. Kremer; M. G. M. Olde Rikkert; M. E. Skehan; S. M. Greenberg

2009-01-01

72

Glycolipid Analysis of Different Tissues and Cerebrospinal Fluid in Type II Gaucher Disease  

Microsoft Academic Search

The lipid composition or the liver, spleen, brain, cerebellum and cerebrospinal fluid of a Gaucher disease type II patient who died at the age of 5 months was examined. The glycolipid analysis demonstrated a marked increase of total amounts not only in the peripheral tissues but also in the brain cerebellum and cerebrospinal fluid, with a prevalence of glucosylceramide. A

R. Gornati; B. Berra; G. Montorfano; C. Martini; G. Ciana; P. Ferrari; M. Romano; B. Bembi

2002-01-01

73

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

PAOLA RAPPELLI; RICCARDO ARE; GIUSEPPE CASU; PIER LUIGI FIORI; PIERO CAPPUCCINELLI; ANTONIO ACETI

1998-01-01

74

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

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. PMID:23401751

González-Marrero, Ibrahim; Castañeyra-Ruiz, Leandro; González-Toledo, Juan M; Castañeyra-Ruiz, Agustín; de Paz-Carmona, Hector; Castro, Rafael; Hernandez-Fernaud, Juan R; Castañeyra-Perdomo, Agustín; Carmona-Calero, Emilia M

2013-01-01

75

Evaluation of Microbial Bacterial and Fungal Diversity in Cerebrospinal Fluid Shunt Infection  

PubMed Central

Background Cerebrospinal fluid shunt infection can be recalcitrant. Recurrence is common despite appropriate therapy for the pathogens identified by culture. Improved diagnostic and therapeutic approaches are required, and culture-independent molecular approaches to cerebrospinal fluid shunt infections have not been described. Objectives To identify the bacteria and fungi present in cerebrospinal fluid from children with cerebrospinal fluid shunt infection using a high-throughput sequencing approach, and to compare those results to those from negative controls and conventional culture. Methods This descriptive study included eight children ?18 years old undergoing treatment for culture-identified cerebrospinal fluid shunt infection. After routine aerobic culture of each cerebrospinal fluid sample, deoxyribonucleic acid (DNA) extraction was followed by amplification of the bacterial 16S rRNA gene and the fungal ITS DNA region tag-encoded FLX-Titanium amplicon pyrosequencing and microbial phylogenetic analysis. Results The microbiota analyses for the initial cerebrospinal fluid samples from all eight infections identified a variety of bacteria and fungi, many of which did not grow in conventional culture. Detection by conventional culture did not predict the relative abundance of an organism by pyrosequencing, but in all cases, at least one bacterial taxon was detected by both conventional culture and pyrosequencing. Individual bacterial species fluctuated in relative abundance but remained above the limits of detection during infection treatment. Conclusions Numerous bacterial and fungal organisms were detected in these cerebrospinal fluid shunt infections, even during and after treatment, indicating diverse and recalcitrant shunt microbiota. In evaluating cerebrospinal fluid shunt infection, fungal and anaerobic bacterial cultures should be considered in addition to aerobic bacterial cultures, and culture-independent approaches offer a promising alternative diagnostic approach. More effective treatment of cerebrospinal fluid shunt infections is needed to reduce unacceptably high rates of reinfection, and this work suggests that one effective strategy may be reduction of the diverse microbiota present in infection.

Simon, Tamara D.; Pope, Christopher E.; Browd, Samuel R.; Ojemann, Jeffrey G.; Riva-Cambrin, Jay; Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Zerr, Danielle M.; Hoffman, Lucas

2014-01-01

76

LDH isoenzymes in cerebrospinal fluid in various brain tumours.  

PubMed Central

This study examined the isoenzymatic pattern of LDH in the cerebrospinal fluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage.

Lampl, Y; Paniri, Y; Eshel, Y; Sarova-Pinhas, I

1990-01-01

77

Serum and Cerebrospinal Fluid Levels of Colistin in Pediatric Patients?  

PubMed Central

Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 ?g/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 ?g/ml but increased in the presence of meningitis (?0.5 ?g/ml or 34 to 67% of serum levels).

Antachopoulos, Charalampos; Karvanen, Matti; Iosifidis, Elias; Jansson, Britt; Plachouras, Diamantis; Cars, Otto; Roilides, Emmanuel

2010-01-01

78

Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies.  

PubMed

We report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinal fluid homocarnosine, a central nervous system-specific peptide, was increased twofold in patients with autosomal dominant bilateral stripallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increases, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6-[18F]fluoro-L-dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway. PMID:1586138

Manyam, B V; Bhatt, M H; Moore, W D; Devleschoward, A B; Anderson, D R; Calne, D B

1992-04-01

79

Cerebrospinal fluid biomarkers of Alzheimer's disease in healthy elderly.  

PubMed

Numerous studies have shown that Alzheimer's Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinal fluid (CSF) biomarkers that reflect AD pathology: amyloid beta, total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly. PMID:23747874

Randall, Catherine; Mosconi, Lisa; de Leon, Mony; Glodzik, Lidia

2013-01-01

80

The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond  

PubMed Central

The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury.

Zappaterra, Mauro W.; Lehtinen, Maria K.

2013-01-01

81

Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid.  

PubMed

This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinal fluid (CSF) samples were obtained from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased levels of oleoylethanolamide in CSF (P = 0.011) but not in serum (P = 0.068) after 24 h of sleep deprivation. Oleoylethanolamide is an endogenous lipid messenger that is released after neural injury and activates peroxisome proliferator-activated receptor-alpha (PPAR-alpha) with nanomolar potency. Exogenous PPAR-alpha agonists, such as hypolipidemic fibrates and oleoylethanolamide, exert both neuroprotective and neurotrophic effects. Thus, our results suggest that oleoylethanolamide release may represent an endogenous neuroprotective signal during sleep deprivation. PMID:19137236

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

2009-03-01

82

Cerebrospinal fluid biomarkers of Alzheimer's disease in cognitively healthy elderly  

PubMed Central

Numerous studies have shown that Alzheimer’s Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinal fluid (CSF) biomarkers that reflect AD pathology: amyloid beta (Aß42), total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly.

Randall, Catherine; Mosconi, Lisa; de Leon, Mony; Glodzik, Lidia

2014-01-01

83

Cerebrospinal fluid and blood biomarkers in Alzheimer's disease  

PubMed Central

Due to an ever aging society and growing prevalence of Alzheimer’s disease (AD), the challenge to meet social and health care system needs will become increasingly difficult. Unfortunately, a definite ante mortem diagnosis is not possible. Thus, an early diagnosis and identification of AD patients is critical for promising, early pharmacological interventions as well as addressing health care needs. The most advanced and most reliable markers are ?-amyloid, total tau and phosphorylated tau in cerebrospinal fluid (CSF). In blood, no single biomarker has been identified despite an intense search over the last decade. The most promising approaches consist of a combination of several blood-based markers increasing the reliability, sensitivity and specificity of the AD diagnosis. However, contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult. In this review, we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.

Humpel, Christian; Hochstrasser, Tanja

2011-01-01

84

Continuous sampling for determination of pharmacokinetics in rat cerebrospinal fluid.  

PubMed Central

A method for determining drug concentration relationships between plasma and cerebrospinal fluid (CSF) in rats is described. Continuous CSF samples were collected directly from the third anterior ventricle with an indwelling cannula inserted through the bregma point, and drug concentrations were determined by high-pressure liquid chromatography and radioimmunoassay micromethods. Three antibiotics with different abilities to cross the blood-CSF barrier (chloramphenicol, piperacillin, and gentamicin) were tested. This method was found to be reproducible for each drug even if the antibiotic levels were low and the sample volumes very small. Peak CSF concentrations occurred between 0.75 and 1.25 h after injection for all three antibiotics. Percent penetration values at 1 h were 50, 1.2, and 5.4% for chloramphenicol, piperacillin, and gentamicin, respectively.

Meulemans, A; Vicart, P; Mohler, J; Vulpillat, M; Pocidalo, J J

1986-01-01

85

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

2012-01-01

86

Cerebrospinal fluid proteome of patients with acute Lyme disease.  

PubMed

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. PMID:22900834

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

2012-10-01

87

Proteomic analysis of cerebrospinal fluid extracellular vesicles: A comprehensive dataset.  

PubMed

Extracellular vesicles (EVs) are present in human cerebrospinal fluid (CSF), yet little is known about their protein composition. The aim of this study is to provide a comprehensive analysis of the proteome of CSF EVs by electron microscopy and high resolution tandem mass spectrometry (MS/MS) in conjunction with bioinformatics. We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. Out of 1315 proteins, 760 were identified in both CSF pools and about 30% of those were also quantitatively enriched in the EV fraction versus the soluble CSF fraction. The proteome of CSF EVs was enriched in exosomal markers such as alix and syntenin-1, heat shock proteins and tetraspanins and contained a high proportion of brain-derived proteins (n=373). Interestingly, several known biomarkers for neurodegenerative diseases such as the amyloid precursor protein, the prion protein and DJ-1 were identified in the EV fractions. Our dataset represents the first comprehensive inventory of the EV proteome in CSF, underscoring the biomarker potential of this organelle. Further comparative studies on CSF EVs isolated from patients diagnosed with neurological disorders are warranted. Data are available via ProteomeXchange with identifier PXD000608. Biological significance In this study we analyzed the protein composition of extracellular vesicles isolated from pooled samples of human cerebrospinal fluid (CSF). CSF is a colorless fluid surrounding the brain and the spinal cord, important for the physiology of the central nervous system, ensuing mechanical protection, regulation of brain blood flow and elimination of byproducts of the brain. Since brain (patho)physiology is reflected in CSF, this biological fluid represents an ideal source of soluble and vesicle-based biomarkers for neurological diseases. Here we confirm the presence of exosome-like extracellular vesicles in CSF, underscoring a potential role in the physiology of the brain. These extracellular vesicles provide a rich source of candidate biomarkers, representing a brain "fluid biopsy". Most interestingly, the involvement of extracellular vesicles in transferring toxic proteins such as ?-synuclein and ?-amyloid has been postulated as one of the mechanisms involved in the spreading of neurodegeneration to different brain areas. In line with this, we show that human CSF extracellular vesicles contain prionogenic proteins such as the amyloid precursor protein and the prion protein. Delineating the protein composition of extracellular vesicles in CSF is a first and crucial step to comprehend their origin and their function in the central nervous system and to establish their biomarker potential. PMID:24769233

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

2014-06-25

88

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

PubMed

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

2009-11-01

89

Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics.  

PubMed

Axonal damage is a prominent cause of disability and yet its pathogenesis is incompletely understood. Using a xenogeneic system, here we define the bioenergetic changes induced in rat neurons by exposure to cerebrospinal fluid samples from patients with multiple sclerosis compared to control subjects. A first discovery cohort of cerebrospinal fluid from 13 patients with multiple sclerosis and 10 control subjects showed that acute exposure to cerebrospinal fluid from patients with multiple sclerosis induced oxidative stress and decreased expression of neuroprotective genes, while increasing expression of genes involved in lipid signalling and in the response to oxidative stress. Protracted exposure of neurons to stress led to neurotoxicity and bioenergetics failure after cerebrospinal fluid exposure and positively correlated with the levels of neurofilament light chain. These findings were validated using a second independent cohort of cerebrospinal fluid samples (eight patients with multiple sclerosis and eight control subjects), collected at a different centre. The toxic effect of cerebrospinal fluid on neurons was not attributable to differences in IgG content, glucose, lactate or glutamate levels or differences in cytokine levels. A lipidomic profiling approach led to the identification of increased levels of ceramide C16:0 and C24:0 in the cerebrospinal fluid from patients with multiple sclerosis. Exposure of cultured neurons to micelles composed of these ceramide species was sufficient to recapitulate the bioenergetic dysfunction and oxidative damage induced by exposure to cerebrospinal fluid from patients with multiple sclerosis. Therefore, our data suggest that C16:0 and C24:0 ceramides are enriched in the cerebrospinal fluid of patients with multiple sclerosis and are sufficient to induce neuronal mitochondrial dysfunction and axonal damage. PMID:24893707

Vidaurre, Oscar G; Haines, Jeffery D; Katz Sand, Ilana; Adula, Kadidia P; Huynh, Jimmy L; McGraw, Corey A; Zhang, Fan; Varghese, Merina; Sotirchos, Elias; Bhargava, Pavan; Bandaru, Veera Venkata Ratnam; Pasinetti, Giulio; Zhang, Weijia; Inglese, Matilde; Calabresi, Peter A; Wu, Gang; Miller, Aaron E; Haughey, Norman J; Lublin, Fred D; Casaccia, Patrizia

2014-08-01

90

[Spontaneous nerve root cerebrospinal fluid leaks and intracranial hypotension: case report].  

PubMed

Spontaneous intracranial hypotension is a rare syndrome, characterized by pressure in the cerebrospinal fluid ranging between 50 and 70 mmH2O and postural headache. Its diagnosis is made through the clinical presentation, measurement of the cerebrospinal fluid pressure and neurorimage features. The clinical recognition of this pathology has been increasing and the differential diagnosis must be made with inflammatory meningeal processes and tumor. We report a case of spontaneous nerve root cerebrospinal fluid leaks in a 34 year-old man and intracranial hypotension. A literature review was performed evaluating the clinical, diagnostic and therapeutic aspects of this unusual pathology. PMID:12715038

Falavigna, Asdrubal; Ferraz, Fernando Antonio Patriani; Boscato, Giovana; Shimokawa, Marcos

2003-03-01

91

[Management of cerebrospinal fluid fistulae: physiopathology, imaging and treatment].  

PubMed

Cerebrospinal fluid (CSF) fistulae can produce leakage through a defect in the bony skull and meninges into the contiguous air-filled cavities at the base of the skull. The major risk is central nervous system infection. When abundant clear rhinorrhea or otorrhea is present, the diagnosis is obvious and imaging is used to localize the fistula. Computed tomography (CT) with millimetric slices and magnetic resonance imaging (MRI) are the most effective diagnostic tools. CT cisternography, an invasive procedure, should only be used when the diagnosis remains uncertain following CT scan and MRI. When CSF leakage is sparse or intermittent, the diagnosis can be made by measuring beta-2 transferrine in the escaping fluid. CT scan followed by MRI are also useful for making the diagnosis and locating the fistula when exterior leakage is absent. CT scan alone is effective for assessing isolated otorrhea. If the diagnosis remains uncertain after all these studies have been used, the patient should be closely followed clinically and isotopic study or surgery should be considered. PMID:15026731

Domengie, F; Cottier, J P; Lescanne, E; Aesch, B; Vinikoff-Sonier, C; Gallas, S; Herbreteau, D

2004-01-01

92

Cerebrospinal fluid flow in the normal and hydrocephalic human brain.  

PubMed

Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity. PMID:17278586

Linninger, Andreas A; Xenos, Michalis; Zhu, David C; Somayaji, MahadevaBharath R; Kondapalli, Srinivasa; Penn, Richard D

2007-02-01

93

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

2007-01-01

94

Fibrin degradation products in the serum and cerebrospinal fluid of patients with group A meningococcal meningitis.  

PubMed

Forty-one patients suffering from group A meningococcal meningitis in an area within the epidemic meningococcal belt of tropical West Africa were studied. The serum of only two of these patients contained fibrin degradation products (FDPs). The cerebrospinal fluid of 21 of these cases was also examined for FDPs, which were present in 13. Their presence in the cerebrospinal fluid was associated with a poor prognosis. PMID:4212012

Brueton, M J; Tugwell, P; Whittle, H C; Greenwood, B M

1974-05-01

95

Fibrin degradation products in the serum and cerebrospinal fluid of patients with group A meningococcal meningitis  

PubMed Central

Forty-one patients suffering from group A meningococcal meningitis in an area within the epidemic meningococcal belt of tropical West Africa were studied. The serum of only two of these patients contained fibrin degradation products (FDPs). The cerebrospinal fluid of 21 of these cases was also examined for FDPs, which were present in 13. Their presence in the cerebrospinal fluid was associated with a poor prognosis.

Brueton, M. J.; Tugwell, P.; Whittle, H. C.; Greenwood, B. M.

1974-01-01

96

Thiamine deficiency and cerebrospinal fluid 5-hydroxyindoleacetic acid: a preliminary study.  

PubMed Central

In three out of five patients with low cerebrospinal fluid thiamine concentrations, the 5-hydroxyindoleacetic acid (5HIAA) values also were low. All patients received thiamine replacement therapy; they underwent a second lumbar puncture after 13, 6, 7, 5 and 45 days of treatment. In all patients blood and cerebrospinal fluid thiamine values rose after treatment. In those patients with initially low CSF 5HIAA, thiamine treatment increased 5HIAA markedly.

Botez, M I; Young, S N; Bachevalier, J; Gauthier, S

1982-01-01

97

Characterisation of the Pro Opiocortin Family of Peptides in Human Cerebrospinal Fluid  

Microsoft Academic Search

Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinal fluid. Samples of cerebrospinal fluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing’s disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column

Lorraine McLoughlin; P. J. Lowry; Sally J. Ratter; J. Hope; G. M. Besser; Lesley H. Rees

1981-01-01

98

Bell's palsy: electrodiagnostics are not indicative of cerebrospinal fluid abnormalities.  

PubMed

Electrodiagnostic testing (electromyography, electroneuronography, and blink reflex) and cerebrospinal fluid (CSF) examination (cell count, immunoglobulins, and antigen-specific intrathecal immunoglobulin G synthesis against herpes simplex virus, varicella zoster virus, cytomegalovirus, and Borrelia burgdorferi sensu latu) were performed in 56 patients with Bell's palsy. The CSF was normal in 45 patients and abnormal in 11 patients. Acute borreliosis was the most common specific pathological CSF finding (4 of 11). Electromyography revealed abolished volitional activity in 22% of patients with normal CSF and in 36% with pathological CSF. Electroneuronographic tests with an amplitude decrease of more than 90% on the affected side or abolished responses were found in 20% of patients with normal CSF and in 18% with pathological CSF. Abolished orbicularis oculi reflexes were seen in 67% of patients with normal CSF and in 82% with pathological CSF Concerning electrodiagnostic testing, no statistically significant difference between patients with normal and abnormal CSF was found, so we conclude that electrodiagnostic testing has no indicative value for abnormal CSF in Bell's palsy. PMID:11407851

Birkmann, C; Bamborschke, S; Halber, M; Haupt, W F

2001-06-01

99

Endoscopic management of cerebrospinal fluid rhinorrhea: the charing cross experience.  

PubMed

Objective?To describe our experience of cerebrospinal fluid (CSF) rhinorrhea management. Design?Retrospective. Setting?Charing Cross Hospital, London, a tertiary referral center. Participants?Fifty-four patients with CSF rhinorrhea managed from 2003 to 2011. Main outcome measures?Surgical technique; Recurrence. Results?Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with spontaneous and two with traumatic leaks had previous failed repairs in other units. Success rates after first and second surgery were 93% and 100%, respectively. Mean follow-up was 21 months. Four patients, all of spontaneous etiology, had recurrences; three of these underwent successful second repair with three layered technique, and the fourth had complete cessation of the leak after gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic three-layered repair since then averted any further failure in the following 7 years. Mean body mass index was 34.0 kg/m(2) in spontaneous and 27.8 kg/m(2) in traumatic cases (p?

Virk, Jagdeep Singh; Elmiyeh, Behrad; Saleh, Hesham A

2013-04-01

100

Blood-mediated scavenging of cerebrospinal fluid glutamate.  

PubMed

The maintenance of brain extracellular glutamate (Glu) at levels below its excitotoxic threshold is performed by Glu transporters present on glia and neurons as well as on brain capillary endothelial cells which remove brain Glu into blood. The feasibility of accelerating the naturally occurring brain-to-blood Glu efflux was studied using paradigms based on the fate of Glu present in the cerebrospinal fluid or infused into the brain ventricles and monitored before, during, and after decreasing blood Glu levels with pyruvate and oxaloacetate, the respective Glu co-substrates of the blood resident enzymes glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase. Results from cerebroventricular perfusions with [3H]Glu, intracerebroventricular injections of [3H]Glu, and measurements of the basal CSF Glu levels point out to the same conclusion that the intravenous administration of pyruvate and oxaloacetate which decreases blood Glu levels accelerates the brain-to-blood Glu efflux. We conclude that the brain extracellular Glu levels can be controlled in part by the blood Glu levels. The results may provide not only a rational explanation for the inhibition of Glu release and neuroprotective effects of parentally administered pyruvate in hemorrhagic shock and forebrain ischemia but could also outline a potential strategy for the removal of excess Glu in various neurodegenerative disorders. PMID:12969259

Gottlieb, Miroslav; Wang, Yin; Teichberg, Vivian I

2003-10-01

101

Cerebrospinal fluid acetylcholinesterase and choline measurements in Huntington's disease.  

PubMed

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 trial of isoniazid. While mean choline levels adjusted for age were lower compared with controls (P = 0.0007), AChE activity did not differ between HD patients and normal controls. Treatment with isoniazid had no significant effect on CSF choline levels or CSF AChE activity. CSF AChE activity showed a statistically significant increase with advancing age. The reduced level of choline in CSF of HD patients may reflect either a defect in choline transport into the brain or a decrease of choline-phospholipid output from the brain. PMID:2146369

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

1990-08-01

102

Cerebrospinal fluid choline levels are decreased in Parkinson's disease.  

PubMed

We examined acetylcholinsterase (AChE) activity and choline levels in cerebrospinal fluid (CSF) in 16 patients with idiopathic Parkinson's disease and 9 control subjects of corresponding age: 8 were untreated Parkinson's patients; 4 were treated with carbidopa-levodopa (100/1,000 mg/day) for 20 +/- 3 months; and 4 were treated with carbidopa-levodopa (110/1,100 mg/day) for 28 +/- 18 months plus amantadine (200 mg/day) for 16 +/- 8 months. CSF choline levels (nmol/ml) were 2.97 +/- 0.79 (control subjects); 1.31 +/- 0.29 (untreated patients); 1.00 +/- 0.29 (carbidopa-levodopa treated); and 1.26 +/- 0.19 (carbidopa-levodopa/amantadine treated). Choline levels were significantly lower in untreated and treated patients compared to control subjects (p = 0.0001). AChE activity did not differ in Parkinson's disease patients as compared to control subjects. The reduced level of choline in CSF may reflect a deficit in choline transport into the brain or a decrease of choline-phospholipid output from the brain. PMID:2360805

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

1990-06-01

103

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.

2013-01-01

104

The Association of Meningitis with Postoperative Cerebrospinal Fluid Fistula  

PubMed Central

Objective?To determine the risk factors for and the clinical course of postoperative meningitis following lateral skull base surgery and to determine its relationship to cerebrospinal fluid (CSF) fistula. Patients?Patients undergoing lateral skull base surgery between July 1999 and February 2010 at an academic tertiary referral center. All subjects had culture-proven meningitis or suspected bacterial meningitis in the postoperative period. Medical records were compared with the lateral skull base patients who did not develop meningitis. Results?Of 508 procedures, 16 patients developed meningitis (3.1%). The most common diagnosis was acoustic neuroma in 81.3%; 68.8% of patients had a CSF leak prior to onset of meningitis, and 50% received a lumbar drain. The median time from surgery to the onset of meningitis was 12 days with a range of 2 to 880 days. The relative risk of developing meningitis in the setting of postoperative CSF fistula is 10.2 (p?

Allen, Kyle P.; Isaacson, Brandon; Kutz, J. Walter; Purcell, Patricia L.; Roland, Peter S.

2012-01-01

105

Cerebrospinal Fluid Interleukin-6 in Central Nervous System Inflammatory Diseases  

PubMed Central

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

Wullschleger, Alexandre; Kapina, Viktoria; Molnarfi, Nicolas; Courvoisier, Delphine S.; Seebach, Jorg D.; Santiago-Raber, Marie-Laure; Hochstrasser, Denis F.; Lalive, Patrice H.

2013-01-01

106

Clinical implications of acute cerebrospinal fluid changes following iophendylate myelography.  

PubMed

Clinical features and serial cerebrospinal fluid (CSF) samples of 50 patients who underwent myelography with iophendylate were studied. Forty two patients (84%) developed one or more features suggestive of meningism lasting for 2-4 days. There was significant rise in the average (mean) CSF counts from 9.81 in the premyelogram sample to 532.6 at the end of 24 hours (p less than 0.001). Both neutrophil and lymphocyte (p less than 000) count increased. At the end of one week, there was significant decrease of total cells in the CSF to 204 (p less than 0.001). Both, neutrophils and lymphocytes decreased. There was significant rise in total proteins in the 24 hours sample, but the fall at one week was not significant statistically. The sugar and chloride values did not change significantly. All CSF samples were negative for bacterial cultures. In conclusion, a significant proportion of the patients undergoing iophendylate myelography develop clinical features suggestive of meningeal irritation and change in the CSF fractions suggestive of meningitis: however these changes are transient and do not warrant institution of chemotherapy or steroids. PMID:1512716

Mehta, H J; Ramakantan, R; Piparia, D H; Hande, A M; Goel, A; Satoskar, A R; Dastur, F D

1992-01-01

107

Cerebrospinal fluid apolipoprotein E levels in subacute sclerosing panencephalitis.  

PubMed

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

2012-04-01

108

Dynamic Oxygen-Enhanced MRI of Cerebrospinal Fluid  

PubMed Central

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

Mehemed, Taha M.; Fushimi, Yasutaka; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Kido, Aki; Fujimoto, Koji; Sakashita, Naotaka; Togashi, Kaori

2014-01-01

109

Cerebrospinal fluid immunoglobulin abnormalities in systemic lupus erythematosus.  

PubMed Central

Central nervous system (CNS) involvement is a common and important complication in systemic lupus erythematosus. The mechanisms for CNS involvement are poorly understood and reliable diagnostic procedures are lacking. Pairs of serum and cerebrospinal fluid (CSF) specimens from 17 patients with clinical and serological manifestations of systemic lupus erythematosus were analysed. All 11 patients with definite or suspect clinical CNS disorder revealed some kind of abnormality in the CSF, in contrast to three of seven systemic lupus erythematosus patients without CNS disorder. The most prominent findings in systemic lupus erythematosus patients with CNS disorder were immune aberrations with oligoclonal bands on agarose isoelectric focusing (AIF) and elevation of IgG and IgM index, probably reflecting intrathecal production of IgG and IgM respectively. Intrathecal production of antiviral antibodies was found in four of 12 patients by AIF followed by immunofixation and subsequent autoradiography. An enzyme-linked immunoabsorbent assay (ELISA) could not detect autoantibodies against structural brain antigens. Images

Ernerudh, J; Olsson, T; Lindstrom, F; Skogh, T

1985-01-01

110

Dynamic oxygen-enhanced MRI of cerebrospinal fluid.  

PubMed

Oxygen causes an increase in the longitudinal relaxation rate of tissues through its T1-shortening effect owing to its paramagnetic properties. Due to such effects, MRI has been used to study oxygen-related signal intensity changes in various body parts including cerebrospinal fluid (CSF) space. Oxygen enhancement of CSF has been mainly studied using MRI sequences with relatively longer time resolution such as FLAIR, and T1 value calculation. In this study, fifteen healthy volunteers were scanned using fast advanced spin echo MRI sequence with and without inversion recovery pulse in order to dynamically track oxygen enhancement of CSF. We also focused on the differences of oxygen enhancement at sulcal and ventricular CSF. Our results revealed that CSF signal after administration of oxygen shows rapid signal increase in both sulcal CSF and ventricular CSF on both sequences, with statistically significant predominant increase in sulcal CSF compared with ventricular CSF. CSF is traditionally thought to mainly form from the choroid plexus in the ventricles and is absorbed at the arachnoid villi, however, it is also believed that cerebral arterioles contribute to the production and absorption of CSF, and controversy remains in terms of the precise mechanism. Our results demonstrated rapid oxygen enhancement in sulcal CSF, which may suggest inhaled oxygen may diffuse into sulcal CSF space rapidly probably due to the abundance of pial arterioles on the brain sulci. PMID:24956198

Mehemed, Taha M; Fushimi, Yasutaka; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Kido, Aki; Fujimoto, Koji; Sakashita, Naotaka; Togashi, Kaori

2014-01-01

111

Hepatic cerebrospinal fluid pseudocyst: A rare complication of ventriculoperitoneal shunt  

PubMed Central

Background: Ventriculoperitoneal (VP) shunts are among the most frequently performed operations in the management of hydrocephalus. Hepatic cerebrospinal fluid (CSF) pseudocyst is a rare but important complication in patients with a VP shunt insertion. In addition to presenting our own case, we performed a PubMed search to comprehensively illustrate the predisposing factors, clinical picture, diagnostic methods, and surgical treatment. This article represents an update for this condition. Case Description: A 40-year-old male was admitted to a hospital complaining of fever, abdominal distention, and pain. He had undergone a VP shunt for communicating hydrocephalus caused by a head trauma one year earlier. Laboratory studies showed liver enzymes alterations, and imaging studies demonstrated a well-defined intraaxially hepatic cyst with the shunt catheter placed inside. Staphylococcus epidermis was cultured via CSF. After removing the VP shunt and an adequate antibiotic treatment, the complication of hepatic CSF pseudocyst was resolved. Conclusion: Hepatic CSF pseudocyst is a rare complication of a VP shunt. Once the diagnosis is verified and if the CSF is sterile, just simply remove the peritoneal catheter and reposition a new one in the abdomen. We believe that it is not necessary to remove or aspirate the hepatic intraaxial pseudocyst, because of the risk of bleeding. In case of CSF infection, the VP shunt can be removed and/or an external derivation can be made, and after treatment with antibiotics, a new VP shunt is placed in the opposite side of the peritoneum.

Dabdoub, Carlos B.; Fontoura, Emilio A.; Santos, Egmond A.; Romero, Paulo C.; Diniz, Cristiano A.

2013-01-01

112

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))

1991-05-01

113

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

2013-01-01

114

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.

2010-01-01

115

Endoscopic Management of Cerebrospinal Fluid Rhinorrhea: The Charing Cross Experience  

PubMed Central

Objective?To describe our experience of cerebrospinal fluid (CSF) rhinorrhea management. Design?Retrospective. Setting?Charing Cross Hospital, London, a tertiary referral center. Participants?Fifty-four patients with CSF rhinorrhea managed from 2003 to 2011. Main outcome measures?Surgical technique; Recurrence. Results?Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with spontaneous and two with traumatic leaks had previous failed repairs in other units. Success rates after first and second surgery were 93% and 100%, respectively. Mean follow-up was 21 months. Four patients, all of spontaneous etiology, had recurrences; three of these underwent successful second repair with three layered technique, and the fourth had complete cessation of the leak after gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic three-layered repair since then averted any further failure in the following 7 years. Mean body mass index was 34.0 kg/m2 in spontaneous and 27.8 kg/m2 in traumatic cases (p?

Virk, Jagdeep Singh; Elmiyeh, Behrad; Saleh, Hesham A.

2013-01-01

116

Free and bound propofol concentrations in human cerebrospinal fluid  

PubMed Central

Aims The aim of this study was to define the relationship between unbound propofol concentrations in plasma and total drug concentrations in human cerebrospinal fluid (CSF), and to determine whether propofol exists in the CSF in bound form. Methods Forty-three patients (divided into three groups) scheduled for elective intracranial procedures and anaesthetized by propofol target control infusion (TCI) were studied. Blood and CSF samples (taken from the radial artery, and the intraventricular drainage, respectively) from group I (17 patients) were used to investigate the relationship between unbound propofol concentration in plasma and total concentration of the drug in CSF. CSF samples taken from group II (18 patients) were used to confirm the presence of the bound form of propofol in this fluid. The CSF and blood samples taken from group III (eight patients) were used to monitor the course of free and bound CSF propofol concentrations during anaesthesia. Results For group I patients the mean (and 95% confidence interval) total plasma propofol concentration was 6113 (4971, 7255) ng ml?1, the mean free propofol concentration in plasma was 63 (42, 84) ng ml?1, and the mean total propofol concentration in CSF was 96 (76, 116) ng ml?1 (P < 0.05 for the difference between the last two values). For group II patients the fraction of free propofol in CSF was 31 (26, 37)%. For group III patients the fraction of free propofol in CSF during TCI was almost constant (about 36%). Conclusions The unbound propofol concentration in plasma was not equal to its total concentration in CSF and cannot be directly related to the drug concentration in the brain. Binding of propofol to components of the CSF may be an additional mechanism regulating the transport of the drug from blood into CSF.

Dawidowicz, Andrzej L; Kalitynski, Rafal; Fijalkowska, Anna

2003-01-01

117

Cerebrospinal Fluid miRNA Profile in HIV-Encephalitis†  

PubMed Central

MicroRNAs are short non-coding RNAs that modulate gene expression by translational repression. Because of their high stability in intracellular as well as extracellular environments, miRNAs have recently emerged as important biomarkers in several human diseases. However, they have not been tested in the cerebrospinal fluid (CSF) of HIV-1 positive individuals. Here, we present results of a study aimed at determining the feasibility of detecting miRNAs in the CSF of HIV-infected individuals with and without encephalitis (HIVE). We also evaluated similarities and differences between CSF and brain tissue miRNAs in the same clinical setting. We utilized a high throughput approach of miRNA detection arrays and identified differentially expressed miRNAs in the frontal cortex of three cases each of HIV+, HIVE, and HIV? controls, and CSF of ten HIV-positive and ten HIV-negative individuals. For the CSF samples, the group of HIV+ individuals contained nine cases of HIV-Associated Neurological Disorders (HAND) and, among those, four had HIVE. All the HIV-negative samples had non-viral acute disseminate encephalomyelitis. A total of 66 miRNAs were found differentially regulated in HIV+ compared to HIV? groups. The greatest difference in miRNA expression was observed when four cases of HIVE were compared to five non-HIVE cases, previously normalized with the HIV-negative group. After statistical analyses, eleven miRNAs were fund significantly up-regulated in HIVE. Although more clinical samples should be examined, this work represents the first report of CSF miRNAs in HIV-infection and offers the basis for future investigation.

Pacifici, Marco; Delbue, Serena; Ferrante, Pasquale; Jeansonne, Duane; Kadri, Ferdous; Nelson, Steve; Velasco-Gonzalez, Cruz; Zabaleta, Jovanny; Peruzzi, Francesca

2012-01-01

118

Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease  

PubMed Central

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

Fraisier, Christophe; Papa, Anna; Granjeaud, Samuel; Hintzen, Rogier; Martina, Byron; Camoin, Luc; Almeras, Lionel

2014-01-01

119

Cerebrospinal Fluid PKR Level Predicts Cognitive Decline in Alzheimer's Disease  

PubMed Central

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

Lapalus, Pauline; Prevot, Magali; Laplanche, Jean-Louis

2013-01-01

120

Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson's disease and other synucleinopathies  

PubMed Central

Central catecholamine deficiency characterizes ?-synucleinopathies such as Parkinson’s disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson’s disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinal fluid catechols were assayed in 146 subjects—108 synucleinopathy patients (34 Parkinson’s disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinal fluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson’s disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinal fluid dihydroxyphenylacetic acid [0.86?±?0.09 (SEM), 1.00?±?0.09, 1.32?±?0.12?nmol/l] than controls (2.15?±?0.18?nmol/l; P?cerebrospinal fluid neurochemical evidence for central dopamine and norepinephrine deficiency. Parkinson’s disease and pure autonomic failure involve differential dopaminergic versus noradrenergic lesions. Cerebrospinal fluid dihydroxyphenylacetic acid seems to provide a sensitive means to identify even early Parkinson’s disease.

Holmes, Courtney; Sharabi, Yehonatan

2012-01-01

121

Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.  

PubMed Central

The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinal fluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinal fluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinal fluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinal fluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis.

Tucker, R M; Williams, P L; Arathoon, E G; Levine, B E; Hartstein, A I; Hanson, L H; Stevens, D A

1988-01-01

122

Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.  

PubMed

The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinal fluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinal fluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinal fluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinal fluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis. PMID:2835002

Tucker, R M; Williams, P L; Arathoon, E G; Levine, B E; Hartstein, A I; Hanson, L H; Stevens, D A

1988-03-01

123

Abnormal protein patterns in blood serum and cerebrospinal fluid detected by capillary electrophoresis  

Microsoft Academic Search

Capillary zone electrophoresis and high-resolution agarose gel electrophoresis were compared to detect protein components in serum and cerebrospinal fluid of patients. Both electrophoretic methods proved to be useful for detection of protein abnormalities (e.g., mono- and oligoclonal bands) in biological fluids, but capillary electrophoresis offered several important advantages, such as sample application without preliminary concentration, lack of staining procedures, and

Mariella Ivanova; Elena Tzvetanova; Veska Jetcheva; Ferenc Kilár

2002-01-01

124

Transmission of cerebrospinal fluid pressure changes to the inner ear and its effect on cochlear microphonics  

Microsoft Academic Search

Alterations in inner ear fluid pressure and cochlear microphonics (CM) associated with increased cerebrospinal fluid (CSF) pressure were studied in the guinea pig. Hydrostatic pressure in the endolymph and perilymph of the cochlea were measured by use of a servo-controlled micropipet system. Endolymphatic and perilymphatic pressure increased in a linear manner with little or no time lag following pressure increases

M. Yoshida; T. Uemura

1991-01-01

125

Perfusion fluids used in neurosurgery affect cerebrospinal fluid and surrounding brain parenchyma in the rat ventriculocisternal perfusion model.  

PubMed

ARTCEREB, an irrigation and perfusion solution (Artcereb), is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate its effects on cerebrospinal fluid (CSF) and on the surrounding cerebrospinal parenchyma. To confirm the kinetics of the perfusion fluid component, we performed whole body autoradiography and examined glucose balance during ventriculocisternal perfusion with (14)C-glucose labeled Artcereb in the rat model, which simulates ventricular irrigation or ventriculocisternal perfusion in clinical neurosurgery. We also performed ventriculocisternal perfusion with Artcereb, lactated Ringer's solution, or normal saline, and observed the effect of these solutions on animal condition and on brain tissue morphology. In the kinetic study, diffusion of (14)C-glucose from the perfused Artcereb to the cerebrospinal tissue was seen on whole body autoradiography, and almost 90% of the glucose in the perfusion fluid was distributed to the cerebrospinal tissue and the systemic circulation. These data indicated that the perfusion fluid interacted actively with the CSF, surrounding parenchyma and the systemic circulation, and suggested that the formation of perfusion fluid affected CSF composition and cerebrospinal tissue functions. Animals perfused with normal saline were associated with serious symptoms including tonic convulsions and death, and exhibited neuronal death in the cerebrum. However, these severe changes were not observed in animals perfused with Artcereb or lactated Ringer's solution. We therefore propose that during neurosurgery, it is extremely important to use a physiological solution like Artcereb which closely resembles normal human CSF, in order to maintain cerebrospinal function and to alleviate postoperative adverse events. PMID:19797859

Doi, Kazuhisa; Morioka, Yujiro; Nishimura, Masuhiro; Kawano, Takeshi; Harada, Daisuke; Naito, Shinsaku; Yamauchi, Aiko

2009-10-01

126

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

2010-01-01

127

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

2009-01-01

128

Cerebrospinal fluid leaks of temporal bone origin: selection of surgical approach.  

PubMed

Cerebrospinal fluid leaks of the temporal bone are rare, often occult, and sometimes challenging to localize and repair. This is a retrospective study of eight patients with spontaneous cerebrospinal fluid leak and six patients with cerebrospinal fluid leak or encephalocele discovered during chronic ear surgery who were treated in a tertiary medical center over a 5-year period. All received preoperative temporal bone computed tomography, and six also underwent magnetic resonance imaging, one computed tomography cisternography, and one radionuclide cisternography. All patients initially underwent a transmastoid surgical approach. Additional exposure was necessary in three patients; two underwent middle fossa craniotomy and another required minicraniotomy. Primary surgical repair was successful in six of the eight patients with spontaneous leaks and in all six chronic ear patients. Both recurrences required intradural middle fossa repair. An individualized approach should be taken for repair of temporal bone cerebrospinal fluid leaks. In this series, most were successfully repaired in a single stage using a transmastoid or combined approach. The transmastoid approach provides information about the precise size and location of the dural defect. A primary transcranial approach is needed for defects that are multiple, located in the petrous apex, and in revision cases. PMID:21311618

Pelosi, Stanley; Bederson, Joshua B; Smouha, Eric E

2010-07-01

129

Cerebrospinal Fluid Adrenomedullin Concentration Correlates with Hyponatremia and Delayed Ischemic Neurological Deficits after Subarachnoid Hemorrhage  

Microsoft Academic Search

Background: Adrenomedullin (AM), a vasorelaxant peptide, is secreted into the cerebrospinal fluid (CSF) from the choroid plexus and can exert natriuretic effects in the kidney. CSF AM concentration is elevated 7–10 days after the onset of aneurysmal subarachnoid hemorrhage (SAH). The aim of the present study was to determine whether CSF AM concentrations correlate with hyponatremia and delayed ischemic neurological

Yoshitaka Kubo; Kuniaki Ogasawara; Shunsuke Kakino; Hiroshi Kashimura; Kenji Yoshida; Akira Ogawa

2008-01-01

130

Epidermal growth factor in human cerebrospinal fluid: reduced levels in amyotrophic lateral sclerosis  

Microsoft Academic Search

Epidermal growth factor (EGF), a mitogenic peptide, is widely distributed within the brain and endocrine cells of the gastro-intestinal tract. Using EGF radioreceptor assay, the EGF level was measured in lumbar cerebrospinal fluid from five patients with amyotrophic lateral scerlosis (ALS) and seven patients with intervertebral disc disease as a control group. The patients with ALS showed reduced EGF levels

D. Cie?lak; J. Szulc-Kuberska; H. Stepiefi; A. Klimek

1986-01-01

131

Excitatory amino acids and taurine levels in cerebrospinal fluid of hypoxic ischemic encephalopathy in newborn  

Microsoft Academic Search

The recent studies indicating the transiently enhanced expression of excitatory amino acid receptors in hypoxia vulnerable brain regions and the elevated concentration of aspartate and glutamate in cerebrospinal fluid of asphyxiated newborns strongly suggest the role of excitatory amino acids in hypoxic ischemic brain damage in the developing human brain. In this study, we compared the concentrations of glutamate, aspartate,

K?v?lc?m Gücüyener; Y?ld?z Atalay; Yusuf Ziya Aral; Alev Hasano?lu; Canan Türky?lmaz; Gürsel Bibero?lu

1999-01-01

132

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study  

Microsoft Academic Search

BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS:

Martijn Weisfelt; Diederik van de Beek; Lodewijk Spanjaard; Johannes B Reitsma; Jan de Gans

2006-01-01

133

Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia  

Microsoft Academic Search

Background: Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme is also found in the cerebrospinal fluid (CSF), where it may prove useful as a marker of dysfunctional PI signal transduction.Methods: IMPase activity was measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic patients. In addition, and

John R Atack; Joseph Levine; Robert H Belmaker

1998-01-01

134

Higher cerebrospinal fluid homovanillic acid levels in depressed patients with comorbid posttraumatic stress disorder  

Microsoft Academic Search

Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects

Leo Sher; Maria A. Oquendo; Shuhua Li; Ainsley K. Burke; Michael F. Grunebaum; Gil Zalsman; Yung-yu Huang; J. John Mann

2005-01-01

135

alpha-Ketoglutaric Acid and Pyruvic Acid in Blood, Cerebrospinal Fluid and Urine  

Microsoft Academic Search

DETERMINATIONS of alpha-ketoglutaric acid and pyruvic acid in blood, cerebrospinal fluid and urine have been carried out using 2,4-dinitrophenylhydrazone method.1 The keto-acid hydrazones were separated, either by paper electrophoresis or by paper chromatography.

E. Zelnicek

1959-01-01

136

Lumbosacral Cerebrospinal Fluid Volume in Humans Using Three-Dimensional Magnetic Resonance Imaging  

Microsoft Academic Search

BACKGROUND: The clinical response to spinal anesthesia is influenced by lumbosa- cral cerebrospinal fluid (CSF) volume, which is highly variable among patients. METHODS: Lumbosacral magnetic resonance images were obtained in 71 patients using a long echo time (TE 198 msec), fast spin echo sequence with fat suppression. Three-dimensional images were created and lumbosacral CSF volume was estimated using a threshold-based

John T. Sullivan; Sharon Grouper; Matthew T. Walker; Todd B. Parrish; Robert J. McCarthy; Cynthia A. Wong

2006-01-01

137

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

Microsoft Academic Search

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

YI-WEI TANG; PAUL N. RYS; BARBARA J. RUTLEDGE; P. SHAWN MITCHELL; THOMAS F. SMITH; DAVID H. PERSING

1998-01-01

138

Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections  

Microsoft Academic Search

Background: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited.Objective: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results.Methods: CSF from patients with was tested for human herpesviruses

N W S Davies; L J Brown; J Gonde; D Irish; R O Robinson; A V Swan; J Banatvala; R S Howard; M K Sharief; P Muir

2005-01-01

139

Molecular analysis of cerebrospinal fluid in viral diseases of the central nervous system  

Microsoft Academic Search

The use of nucleic acid (NA) amplification techniques has transformed the diagnosis of viral infections of the central nervous system (CNS). Because of their enhanced sensitivity, these methods enable detection of even low amounts of viral genomes in cerebrospinal fluid. Following more than 10 years of experience, the polymerase chain reaction or other NA-based amplification techniques are nowadays performed in

Paola Cinque; Simona Bossolasco; Åke Lundkvist

2003-01-01

140

Analysis of Cerebrospinal Fluid Flow Waveforms with Gated Phase-Contrast MR Velocity Measurements  

Microsoft Academic Search

PURPOSE: To analyze the characteristics of normal cerebrospinal fluid (CSF) flow waveforms and to relate them to the arterial input and venous output flow waveforms in healthy volunteers. METHODS: Cine phase-contrast MR was obtained in 17 volunteers. The temporal velocity infor- mation from the cervical pericord CSF spaces, basal cisterns, and aqueduct, as well as the internal carotid and vertebral

Rafeeque A. Bhadelia; Andrew R. Bogdan; Samuel M. Wolpert

1995-01-01

141

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity  

Microsoft Academic Search

Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects,

Thomas E. Angel; Jon M. Jacobs; Serena S. Spudich; Marina A. Gritsenko; Dietmar Fuchs; Teri Liegler; Henrik Zetterberg; David G. Camp; Richard W. Price; Richard D. Smith

2012-01-01

142

Pharmacokinetics, cerebrospinal fluid penetration, and metabolism of piroxantrone in the Rhesus monkey  

Microsoft Academic Search

Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activityin vitro and less cardiac toxicity than the anthracyclines. The metabolic pathways and central nervous system penetration of piroxantrone have not been determined. In this study we examined the pharmacokinetic behavior of piroxantrone in plasma and cerebrospinal fluid in a non-human primate model. In addition, a urinary metabolite of piroxantrone was isolated

Stacey L. Berg; Frank M. Balis; Karen S. Godwin; David G. Poplack

1993-01-01

143

The function, composition and analysis of cerebrospinal fluid in companion animals: Part II – Analysis  

Microsoft Academic Search

Accurate analysis of cerebrospinal fluid (CSF) provides a wide range of information about the neurological health of the patient. CSF can be withdrawn from either of two cisterns in dogs and cats using relatively safe techniques. Once CSF has been collected it must be analysed immediately and methodically. Evaluation should consist of macroscopic, quantitative and microscopic analyses. As part of

Roberta Di Terlizzi; Simon R. Platt

2009-01-01

144

[Hexamidine content of the blood plasma and cerebrospinal fluid in patients with epilepsy].  

PubMed

In 74 patients with different attack rates and patterns mean levels of hexamidine in the blood plasma and cerebrospinal fluid were 15.9 micrograms/ml and 7.86 micrograms/ml, respectively, the former almost twice as high as the latter. Both were found to correlate with the drug daily doses and other anticonvulsants administration. PMID:3188751

Gromov, S A; Fedotenkova, T N; Stabrovski?, E M

1988-01-01

145

MR phase imaging and cerebrospinal fluid flow in the head and spine  

Microsoft Academic Search

Motion of the cerebrospinal fluid (CSF) in and around the brain and spinal cord was examined in healthy subjects and in a number of patients with abnormalities of the CSF circulation. The pulsatile motion of the CSF was determined by spin echo phase (velocity) imaging, sometimes in combination with gradient echo phase contrast cine. Differences in flow patterns across CSF

L. M. Levy; G. Di Chiro

1990-01-01

146

Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia  

Microsoft Academic Search

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

Håkan Karlsson; Silke Bachmann; Johannes Schroder; Justin McArthur; E. Fuller Torrey; Robert H. Yolken

2001-01-01

147

High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid  

Microsoft Academic Search

The concentration of lead in blood, serum, cerebrospinal fluid, and urine was measured in patients with neurological disease and in control subjects including cases of plumbism. A plot of blood lead versus serum lead resembles the familiar curves of blood lead versus either free erythrocyte porphyrin or urinary delta-aminolaevulinic acid in that serum lead is constant up to a blood

W I Manton; J D Cook

1984-01-01

148

High level of pyridoxal 5'-phosphate in the cerebrospinal fluid of adult celiac patients.  

PubMed

Adults with intestinal malabsorption due to celiac disease show reduced central serotonin metabolism, probably induced by a lack of essential dietary factors. Investigating a role proposed for vitamin B6 deficiency, a regular finding in untreated celiacs, the present study yields no support for the hypothesis that direct inhibition at the decarboxylation step by vitamin B6 deficiency accounts for low central serotonin turnover in adult celiacs: 11 untreated patients showing reduced 5-HIAA in the cerebrospinal fluid (71+/- 26.8 pmol/ml) had a significantly higher concentration of the metabolically active B6 vitamer pyridoxal 5'-phosphate in lumbar cerebrospinal fluid (0.06 +/- 0.34 ng/ml) than controls (0.24 +/- 0.07 ng/ml) (p less than 0.01). Cerebrospinal fluid tryptophan, precursor of serotonin, was normal (2035 %/- 649 pmol/ml). Raised pyridoxal 5'-phosphate in the cerebrospinal fluid in untreated celiac disease is an unexpected finding. Possibly it is secondary to the diminished central monamine metabolism in these patients, but further studies are needed bearing in mind that mental depression is a major cause for disability in adult celiac disease. PMID:6182788

Hallert, C; Allenmark, S; Larsson-Cohn, U; Sedvall, G

1982-11-01

149

Double ring formation in single radial immunodiffusion for kappa chains in multiple sclerosis cerebrospinal fluid  

Microsoft Academic Search

Double ring formation in single radial immunodiffusion for light chains of type kappa and not for light chains of type lambda was observed in cerebrospinal fluid in 24 out of 42 patients with multiple sclerosis, 1 patient with cerebral cysticercosis, 1 of 3 patients with neurosyphilis and 1 patient with spastic paraparesis of unknown eitology. Double ring formation was not

H. Iwashita; F. Grunwald; H. Bauer

1974-01-01

150

Vasopressin enhances the clearance of beta-endorphin immunoreactivity from rat cerebrospinal fluid.  

PubMed

The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of beta-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4-9) (1.44 fmol), N alpha-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of beta-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1-9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied beta-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel beta-endorphin-(1-31), the beta-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of beta-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lives of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol beta-endorphin-(1-31)) significantly enhanced the disappearance of beta-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of beta-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain. PMID:2138399

Sweep, C G; Boomkamp, M D; Barna, I; Logtenberg, A W; Wiegant, V M

1990-02-01

151

Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection.  

PubMed Central

We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinal fluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection.

Narita, M; Yamada, S; Matsuzono, Y; Itakura, O; Togashi, T; Kikuta, H

1996-01-01

152

Skull base osteosarcoma presenting with cerebrospinal fluid leakage after CyberKnife® treatment: a case report  

PubMed Central

Introduction CyberKnife® radiation is an effective treatment for unresectable skull base tumors because it can deliver a highly conformational dose distribution to the complex shapes of tumor extensions. There have been few reports of severe complications with this treatment. This is the first published case report to our knowledge of cerebrospinal fluid leakage induced by CyberKnife® radiotherapy. Case presentation A skull base tumor was identified on magnetic resonance imaging in a 78-year-old Asian woman with a headache in her forehead. An endoscopic transnasal tumor resection was performed; however, the tumor, invading into the cavernous sinuses and optic canal, was not completely removed. During the subtotal resection of the tumor, no cerebrospinal fluid leakage was observed. Osteosarcoma was histologically diagnosed, and CyberKnife® radiation was performed to the residual tumor considering the aggressive feature of the tumor with a molecular immunology Borstel-1 index of 15%. Five months after the treatment, magnetic resonance imaging showed definite tumor shrinkage, and the patient had been living her daily life without any troubles. After another month, the patient was transferred to our clinic because of coma with high fever, and computed tomography demonstrated severe pneumocephalus. Rhinorrhea was definitely identified on admission; therefore, emergency repair of the cerebrospinal fluid leakage was performed using an endoscope. Dural defects at the bottom of the sella turcica were identified under careful endoscopic observation and fat tissue was patched to the dural defects. Follow-up computed tomography proved complete disappearance of air from the cisterns 2 weeks after the surgery, and the patient was discharged from our hospital without any neurological deficits. Conclusion CyberKnife® radiation is one of the effective treatments for skull base tumors; however, the risk of cerebrospinal fluid leakage should be considered when tumor invasion to the dura mater is suspected. Emergency surgical treatment is required when cerebrospinal fluid leakage is induced by the radiotherapy because the leakage is not expected to be healed by palliative treatments.

2013-01-01

153

Echographic correlation of optic nerve sheath size and cerebrospinal fluid pressure.  

PubMed

A 23-year-old obese woman presented with papilledema. Computed tomography showed no intracranial mass lesions and lumbar puncture revealed an increased opening pressure, confirming the diagnosis of pseudo-tumor cerebri. Standardized echography of the optic nerves was performed immediately before and after lumbar puncture. A marked reduction of cerebrospinal fluid pressure correlated with a decrease in the subarachnoid fluid of the optic nerve sheath. PMID:2526162

Galetta, S; Byrne, S F; Smith, J L

1989-06-01

154

A reusable adapter for collection of cerebrospinal fluid in chronically cannulated goats.  

PubMed

A lightweight, adjustable adapter has been designed for chronic cannulation of goats (Capra hircus) which provides an accurate, safe means of sampling cerebrospinal fluid (CSF). This cisternal cannula has been used for continuous perfusion of synthetic CSF into the fourth ventricle in unanesthetized goats. This method also has been used for examining changes in ionic composition of the CSF and cerebral interstitial fluid (ISF) during physiologic adaptations to high altitude (2-5). PMID:2811283

Forte, V A; Devine, J A; Cymerman, A

1989-09-01

155

Beta2-Microglobulin as a Diagnostic Marker in Cerebrospinal Fluid: A Follow-Up Study  

PubMed Central

Beta2-Microglobulin (?2-m) is a low molecular weight protein occurring in all body fluids. Its concentration increases in various pathologies. Increased values in cerebrospinal fluid (CSF) are ascribed to an activation of immune system. Using immunoturbidimetry, we examined concentrations of beta2-microglobulin in cerebrospinal fluid in a large group of 6274 patients with defined neurological diseases. Cell counts, total protein, albumin, glucose, lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also evaluated. We found substantial changes of CSF ?2-m concentrations in purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis, and neuroborreliosis, while in multiple sclerosis these changes were not significant. Intrathecal synthesis and immune activation were present in these clinical entities. A new normative study enables better understanding of beta2-microglobulin behavior in CSF.

Svatonova, Jana; Borecka, Klara; Adam, Pavel; Lanska, Vera

2014-01-01

156

Pregnancy and vaginal delivery in epidural analgesia in woman with cerebrospinal fluid shunt.  

PubMed

Hydrocephalus is a medical condition characterized by enlargement of cerebral ventricles due to abnormal cerebrospinal fluid accumulation. Hydrocephalic women with cerebrospinal fluid (CSF) shunts are now surviving to reproductive age, but still there are doubts regarding the mode of delivery, analgesia and anesthesia. Postpartal complications are more frequently described in deliveries ended by cesarean section than in spontaneous vaginal deliveries. We present a case of labor in the 32-year old woman, with congenital hydrocephalus and a preexisting ventriculoperitoneal (VP) shunt. After thorough review of current literature, we came to conclusion that without absolute neurosurgical indication or acute development of listed symptoms (headaches, irritability, light sensitivity, hyperesthesia nausea, vomiting, vertigo, migraines, seizures, weakness in the arms or legs, strabismus and double vision) the best way to finish the pregnancy of woman with VP shunt is spontaneous vaginal delivery with the use of epidural analgesia, mediolateral episiotomy and vacuum extraction. PMID:24611354

Bursac, Danijel; Kulas, Tomislav; Persec, Jasminka; Persec, Zoran; Dui?, Zeljko; Partl, Jasenka Zmijanac; Glavi?, Zeljko; Hrgovi?, Zlatko; Bojani?, Katarina

2013-12-01

157

Observation of spontaneous cerebrospinal fluid rhinorrhoea to body mass index: a preliminary report.  

PubMed

The purpose of this retrospective study is to determine whether there is a correlation among overweight, gender and the risk of development of spontaneous cerebrospinal fluid (CSF) rhinorrhoea. The clinical data of eight patients diagnosed with spontaneous cerebrospinal fluid rhinorrhoea who had been treated at our tertiary referral centre between 1998 and 2007 were assessed. Demographically, seven patients were female and one male with ages ranging from 14 to 53 years with a mean age of 43.6 years. This observation revealed that all patients were overweight with a mean body mass index (BMI) of 32.5 kg/m2. This study suggests that there is a trend of increasing BMI to the risk of developing a spontaneous CSF rhinorrhoea. PMID:18705467

Gendeh, B S; Salina, H

2007-12-01

158

Antibodies to antigen A60 in cerebrospinal fluid from patients with tuberculous meningitis  

Microsoft Academic Search

Cerebrospinal fluid (CSF) anti-mycobacterial antigen 60 (A60) IgM, IgG and IgA in patients affected by meningitis of different etiologies were assayed as a rapid diagnostic test in cases of tuberculous meningitis. A commercial EIA was used to test 127 CSF samples classified as follows: tuberculous meningitis (n=27 CSF samples from 16 patients, 6 of them with AIDS), pyogenic meningitis (n=13),

L. F. López-Cortés; M. C. Nogales-Pérez; J. Gómez-Mateos; D. Jiménez-Hernández; E. Jiménez-Mejias; J. Pachón-Diaz

1994-01-01

159

Identification of neuropeptide FF-related peptides in human cerebrospinal fluid by mass spectrometry  

Microsoft Academic Search

Several neuropeptide FF (NPFF)-related peptides, known as modulators of the opioid system, have been previously characterized in bovine and rodent brain. Reverse-phase high pressure liquid chromatography (HPLC) fractions of a human with normal pressure hydrocephalus cerebrospinal fluid (CSF), co-migrating with NPFF-related synthetic peptides, were characterized by capillary HPLC coupled on-line to nanospray ion trap tandem mass spectrometry. Two peptides present

Odile Burlet-Schiltz; Honoré Mazarguil; Jean-Christophe Sol; Patrick Chaynes; Bernard Monsarrat; Jean-Marie Zajac; Anne Roussin

2002-01-01

160

Cerebrospinal Fluid Levels of Nitric Oxide and Nitrotyrosine in Neonates With Mild Hypoxic-Ischemic Encephalopathy  

Microsoft Academic Search

The objective of this study was to determine the role of cerebral nitric oxide and its powerful oxidant peroxynitrite following mild birth asphyxia. The cerebrospinal fluid levels of nitric oxide and 3-nitrotyrosine as a marker for peroxynitrite are measured in neonates with mild hypoxic-ischemic encephalopathy. Based on the classification of Sarnat and Sarnat, term neonates with mild hypoxic-ischemic encephalopathy and

Kivicim Gücüyener; Ebru Ergenekon; Tuncay Demiryürek; Deniz Erbas; Güler Öztürk; Esin Koç; Yildiz Atalay

2002-01-01

161

Hydrocephalus communicans after traumatic upper cervical spine injury with a cerebrospinal fluid fistula: a rare complication  

Microsoft Academic Search

Secondary hydrocephalus communicans after traumatic upper cervical spine injuries with leakage of cerebrospinal fluid is a rare and hardly described complication. A case of a 75-year-old woman sustained a type II dens axis without other injuries, especially without evidence of a hydrocephalus in the primary CT scan. Dorsal atlanto-axial fusion was performed. Postoperative drainage was prolonged and positive for ?2-transferrin.

Ladislav Mica; Valentin Neuhaus; Enrico Pöschmann; Dilek Könü-Leblebicioglu; Urs Schwarz; Guido A Wanner; Clément ML Werner; Hans-Peter Simmen

2010-01-01

162

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

163

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

Microsoft Academic Search

CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinal fluid (CSF) of patients with culture-proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32) and compared these results with levels of other CXC-chemokines, CXCL8-

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

2003-01-01

164

Measurement of resiniferatoxin in cerebrospinal fluid by high-performance liquid chromatography  

Microsoft Academic Search

A sensitive and simple high-performance liquid chromatographic (HPLC) assay was developed for the quantification of resiniferatoxin (RTX) in canine cerebrospinal fluid (CSF). A reversed-phase C18 column and acetonitrile in 0.02 M NaH2PO4 as mobile phase provided satisfactory resolution for RTX analysis. Direct HPLC analysis of the CSF samples without sample extraction or preparation improves the accuracy and detection limits of

Andrew J Mannes; Dorothy Cimino Brown; Sandra Z Perkowski; Jason Keller; Robert M Caudle; Michael J Iadarola; Qing C Meng

2002-01-01

165

Specific and Surrogate Cerebrospinal Fluid Markers in Creutzfeldt–Jakob Disease  

Microsoft Academic Search

\\u000a Detection of cerebrospinal fluid (CSF) biomarkers is a major challenge for laboratories involved in neurological disorder\\u000a diagnostics and the long list of putative markers now available reflects the enormous efforts and the relevance of CSF in\\u000a neurology. The result of these intensive studies on CSF is that specific biomarkers are included as supportive criteria for\\u000a neurodegenerative disorder diagnosis. The diagnostic

Gianluigi Zanusso; Michele Fiorini; Pier Giorgio Righetti; Salvatore Monaco

166

Quantitative analysis of amyloid-  peptides in cerebrospinal fluid using immunoprecipitation and MALDI-Tof mass spectrometry  

Microsoft Academic Search

Immunoprecipitation (IP) combined with matrix-assisted laser desorption ionization (MALDI) time of flight (Tof) mass spectrometry has been used to develop quantitative assays for amyloid-b (Ab) peptides in cerebrospinal fluid (CSF). Inclusion of 15N labelled standard peptides allows for absolute quantification of multiple Ab isoforms in individual samples. Characterization of variability associated with all steps of the assay indicated that the

Valentina Gelfanova; Richard E. Higgs; Robert A. Dean; David M. Holtzman; Martin R. Farlow; Eric R. Siemers; Amechand Boodhoo; Yue-Wei Qian; Xiaohua He; Zhaoyan Jin; Deborah L. Fisher; Karen L. Cox; John E. Hale

2007-01-01

167

High-performance liquid chromatographic determination of ritonavir in human plasma, cerebrospinal fluid and saliva  

Microsoft Academic Search

A simple, ion-pair high-performance liquid chromatographic method has been developed and validated for the quantitative determination of the HIV protease inhibitor ritonavir in human plasma, cerebrospinal fluid and saliva. Sample pretreatment consisted of precipitation of proteins with acetonitrile prior to high-performance liquid chromatography with ultraviolet detection at 239 nm. The method has been validated over the range of 50 ng\\/ml

Richard M. W Hoetelmans; Marjolijn van Essenberg; Monique Profijt; Pieter L Meenhorst; Jan W Mulder; Jos H Beijnen

1998-01-01

168

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

2011-01-01

169

Direct sample injection for capillary electrophoretic determination of organic acids in cerebrospinal fluid  

Microsoft Academic Search

Organic acids in cerebrospinal fluid (CSF) are potential diagnostic markers for neurological diseases and metabolic disorders.\\u000a A capillary electrophoretic (CE) method for the direct analysis, i.e., without any sample preparation, of six organic acids\\u000a in CSF was developed. A capillary coating consisting of a triple layer of charged polymers (polybrene-dextran sulfate-polybrene)\\u000a was used in combination with a negative separation voltage,

Rawi Ramautar; Govert W. Somsen; Gerhardus J. de Jong

2007-01-01

170

Proteomic Discovery of Biomarkers in the Cerebrospinal Fluid of Brain Tumor Patients  

Microsoft Academic Search

Central nervous system (CNS) diseases often induce changes in the protein composition of the cerebrospinal fluid (CSF) as\\u000a this liquid bathes the brain and collects its secreted products. The detection and monitoring of such pathology-related changes\\u000a can be exploited for their relation to tumor growth in the brain. The potential of using differential proteomic profiling\\u000a in CNS malignancies to identify

Fatima W. Khwaja; Erwin G. Van Meir

171

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

2011-01-01

172

Factors Influencing the Measurement of Lysosomal Enzymes Activity in Human Cerebrospinal Fluid  

PubMed Central

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

Parnetti, Lucilla; Eusebi, Paolo; Paciotti, Silvia; De Carlo, Claudia; Codini, Michela; Tambasco, Nicola; Rossi, Aroldo; Agnaf, Omar M. El.; Calabresi, Paolo; Beccari, Tommaso

2014-01-01

173

Hypertonic Saline Reduces Intracranial Hypertension in the Presence of High Serum and Cerebrospinal Fluid Osmolalities  

Microsoft Academic Search

Background  Osmotherapy has been the cornerstone in the management of patients with elevated intracranial pressure (ICP) following traumatic\\u000a brain injury (TBI). Several studies have demonstrated that hypertonic saline (HTS) is a safe and effective osmotherapy agent.\\u000a This study evaluated the effectiveness of HTS in reducing intracranial hypertension in the presence of a wide range of serum\\u000a and cerebrospinal fluid (CSF) osmolalities.

Eduardo Paredes-Andrade; Sarah B. Rockswold; Rick M. Odland; Gaylan L. Rockswold

174

Normal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption in Ventricular Enlargement  

Microsoft Academic Search

CINE phase-contrast MRI (CINE-MRI) was used to measure cerebrospinal fluid (CSF) velocities and flow rates in the brain of\\u000a six normal subjects and five patients with communicating hydrocephalus. Mathematical brain models were created using the MRI\\u000a images of normal subjects and hydrocephalic patients. In our model, the effect of pulsatile vascular expansion is responsible\\u000a for pulsatile CSF flow between the

Andreas A. Linninger; Brian Sweetman; Richard Penn

2009-01-01

175

Cerebrospinal Fluid Analysis Should Be Considered in Patients with Cognitive Problems  

PubMed Central

Hepatologists assay liver enzymes and cardiologists structural heart proteins in serum to diagnose and monitor their patients. This way of thinking has not quite made it into the memory clinics yet, in spite of the availability of validated cerebrospinal fluid biomarkers for key pathological events in the brain in neurodegeneration. Here, we argue that a spinal tap should be considered in all patients who seek medical advice for memory problems and list the highly relevant clinical questions CSF analyses can address.

Zetterberg, Henrik; Mattsson, Niklas; Blennow, Kaj

2010-01-01

176

Evidence of Cellular Immune Activation in Children With Opsoclonus-Myoclonus: Cerebrospinal Fluid Neopterin  

Microsoft Academic Search

To evaluate cellular immune activation in opsoclonus-myoclonus syndrome, we measured the inflammatory marker neopterin in the cerebrospinal fluid of 16 children with opsoclonus-myoclonus and neuroblastoma, 24 children with opsoclonus-myoclonus but no tumor, and 19 age-matched controls. The mean concentration in opsoclonus-myoclonus was 2.3-fold higher than in controls (P = .008). Neopterin was greatly elevated in four of the most neurologically

Michael R. Pranzatelli; Keith Hyland; Elizabeth D. Tate; Lauren A. Arnold; Tyler J. Allison; Gamini S. Soori

2004-01-01

177

Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers  

Microsoft Academic Search

Objective: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzhei- mer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal—HTB (2-hy- droxy-4-trifluoro-methylbenzoic acid)—in healthy vol- unteers. Methods: Data from two studies

M. Valle; M. J. Barbanoj; A. Donner; I. Izquierdo; U. Herranz; N. Klein; H. G. Eichler; M. Müller; M. Brunner

2005-01-01

178

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

179

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

2003-01-01

180

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

2008-01-01

181

Circulating neuroactive peptides and the blood-brain and blood-cerebrospinal fluid barriers.  

PubMed

Interactions of radiolabelled circulating neuroactive peptides: enkephalin-leucine (Enk-Leu), delta sleep inducing peptide (DSIP), thyrotropin-releasing hormone (TRH) and vasopressin-arginine (VP-Arg) with the blood-brain and blood-cerebrospinal fluid barriers were studied by mean of: 1. a vascular perfusion technique in the guinea-pig using multiple-time brain uptake analysis, 2. a vascular perfusion technique of the in situ isolated choroid plexus from sheep using single-circulation paired-tracer dilution or steady-state analysis. It has been demonstrated that Enk-Leu, DSIP and VP-Arg were taken up intact at the luminal side of the blood-brain barrier and blood-tissue interface of the blood-cerebrospinal fluid barrier by a saturable mechanism. On the other hand, a non-saturable mechanism as well as possible enzymatic degradation were shown during TRH interactions with either the blood-brain or blood-cerebrospinal fluid barriers. It is concluded that both, facilitated and simple diffusion, govern circulating neuroactive peptide uptake into the central nervous system. PMID:2193795

Zlokovic, B V; Segal, M B; Davson, H; Lipovac, M N; Hyman, S; McComb, J G

1990-03-01

182

Cerebrospinal fluid cytokines and matrix metalloproteinases in human immunodeficiency seropositive and seronegative patients of tuberculous meningitis  

PubMed Central

Background: Some important clinical differences exist between human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients. Alterations in the cerebrospinal fluid (CSF) cytokines and matrix metalloproteinase have been noted in tuberculous meningitis. In HIV-infected patients, the immunopathogenesis is expected to be different. Materials and Methods: In this study, 64 patients of tuberculous meningitis (28 HIV seropositive and 36 seronegative) were included. The patients were followed up for six months. Cerebrospinal fluid (CSF) samples of tuberculous meningitis patients and 20 controls were subjected to tissue necrosis factor (TNF)-?, interleukin (IL)-1?, interferon (IFN)-?, IL-10, matrix metalloproteinase (MMP)-2, and MMP-9 estimations. The levels were correlated with the patients’ baseline clinical characteristics, CSF parameters, neuroimaging findings, and the outcome. The outcome was assessed and modified with the Barthel index. Results: The CSF cytokines and MMP levels were significantly elevated in tuberculous meningitis when compared with the controls. There was no significant difference seen between HIV seropositive and seronegative tuberculous meningitis, except for the IL-1? level, which was significantly lower in the HIV-infected patients. The cytokine and MMP levels did not correlate with the baseline clinical characteristics, disease severity, cerebrospinal fluid characteristics, neuroimaging findings, and outcome. Conclusion: In conclusion, HIV infection did not affect a majority of the CSF cytokines and MMP levels in tuberculous meningitis except for IL-1? level. None of the estimated inflammatory parameters correlated with the outcome.

Rai, Dheeraj; Garg, Ravindra Kumar; Mahdi, Abbas Ali; Jain, Amita; Verma, Rajesh; Tripathi, Anil Kumar; Singh, Maneesh Kumar; Malhotra, Hardeep Singh; Singh, Gyan Prakash; Ahmad, Mohammad Kaleem

2014-01-01

183

Computational Fluid Dynamics for the Assessment of Cerebrospinal Fluid Flow and Its Coupling with Cerebral Blood Flow  

Microsoft Academic Search

\\u000a The dynamics of cerebrospinal fluid flow are directly linked to those of the ­cardiovascular system. The heart not only drives\\u000a blood flow, but is also at the origin of CSF pulsation through the expansion and contraction of cerebral blood vessels. As\\u000a was detailed in the preceding chapter, CSF dynamics can be altered by diseases and conditions such as hydrocephalus and,

Vartan Kurtcuoglu

184

Cerebrospinal fluid flow dynamics in patients with multiple sclerosis: a phase contrast magnetic resonance study  

PubMed Central

Cerebrospinal fluid (CSF) flow dynamics, which supposedly have a strong relationship with chronic cerebrospinal venous insufficiency (CCSVI), might be expected to be affected in multiple sclerosis (MS) patients. In this study, CSF flow at the level of the cerebral aqueduct was evaluated quantitatively by phase contrast magnetic resonance imaging (PC-MRI) to determine whether CSF flow dynamics are affected in MS patients. We studied 40 MS patients and 40 healthy controls using PC-MRI. We found significantly higher caudocranial (p=0.010) and craniocaudal CSF flow volumes (p=0.015) and stroke volume (p=0.010) in the MS patients compared with the controls. These findings may support the venous occlusion theory, but may also be explained by atrophy-dependent ventricular dilatation independent of the venous theory in MS patients.

Gorucu, Yasin; Albayram, Sait; Balci, Belgin; Hasiloglu, Zehra Isik; Yenigul, Kubilay; Yargic, Fatma; Keser, Zafer; Kantarci, Fatih; Kiris, Adem

185

Isoelectric focusing in agarose gel for detection of oligoclonal bands in cerebrospinal and other biological fluids.  

PubMed

Isoelectric focusing (IEF) coupled with immunodetection (immunofixation or immunoblotting) has become the leading technique for the detection and study of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) and also is increasingly used in other body fluids such as the tear and serum. Limited commercial availability of precast agarose IEF gels for research and a need for customization prompted reporting a detailed general protocol for the preparation and casting of agarose IEF gel along with sample, control, and isoelectric point marker preparation and carrying out the focusing itself for CSF OCBs. However, the method is readily adaptable to the use of other body fluid specimens and, possibly, research specimens such as culture fluids as well. PMID:22585491

Csako, Gyorgy

2012-01-01

186

Abdominal cerebrospinal fluid pseudocyst occurring 21 years after ventriculoperitoneal shunt placement: a case report  

PubMed Central

Background Ventriculoperitoneal shunt (VPS) placement is an established procedure for the treatment of hydrocephalus of diverse etiologies in children and adults. Abdominal cerebrospinal fluid pseudocyst, which is potentially life threatening, is a rare complication and usually occurs during childhood. However, with increasing longevity following successful treatment, it can also occur in adults. Case presentation Here we describe a 22-year-old man who was admitted to our hospital because of diffuse abdominal distention. A VPS was placed 21 years earlier to treat hydrocephalus secondary to spina bifida. Abdominal computed tomography (CT) revealed a homogeneous low-density fluid collection adjacent to the VPS catheter tip, causing stomach obstruction. Thus a peritoneal pseudocyst around VPS was suspected and emergency laparotomy was performed. The large mass was localized in the left upper abdomen between the stomach and mesentery of the transverse colon, exactly at the omental bursa. The cystic mass was opened and 1500 ml of clear fluid was drained; the distal end of the VPS was repositioned outside the mass. Thus, an abdominal cerebrospinal fluid pseudocyst as a complication of VPS was diagnosed. Conclusion Gastroenterological surgeons should be aware of this possible complication, and this complication should be considered during differential diagnosis of an acute abdomen complaint.

2013-01-01

187

Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder  

PubMed Central

Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and verbal memory is common in euthymic bipolar patients. The cerebrospinal fluid has previously been used to study neurodegenerative processes in Alzheimer's disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid ?, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinal fluid biomarkers for neurodegenerative processes. Cerebrospinal fluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid ?1-42, amyloid ?38/?40/?42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid ?42/amyloid ?38 and the amyloid ?42/amyloid ?40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid ?1-42, or amyloid ?38/?40/?42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients.

Jakobsson, Joel; Zetterberg, Henrik; Blennow, Kaj; Johan Ekman, Carl; Johansson, Anette G M; Landen, Mikael

2013-01-01

188

Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study.  

PubMed

Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-?, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1?, IFN-?) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy. PMID:24394344

Dauvilliers, Yves; Jaussent, Isabelle; Lecendreux, Michel; Scholz, Sabine; Bayard, Sophie; Cristol, Jean Paul; Blain, Hubert; Dupuy, Anne-Marie

2014-03-01

189

Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?  

Microsoft Academic Search

In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant

Lena Koh; Andrei Zakharov; Miles Johnston

2005-01-01

190

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

2006-01-01

191

Digital subtraction cisternography: a new approach to fistula localisation in cerebrospinal fluid rhinorrhoea.  

PubMed Central

Positive contrast cisternography with digital subtraction of fluoroscopy images before computed tomography (CT) was employed in the investigation of eight patients with cerebrospinal fluid (CSF) rhinorrhoea. Fistulae were visualised by preliminary digital subtraction cisternography (DSC) in six patients and in five patients the sites of leakage were confirmed at surgery. Fluoroscopy facilitated interpretation of CT in all the positive studies and in two patients provided information which could not be deduced from CT cisternography (CTC) alone. The combined technique is recommended for the investigation of patients with recurrent and post operative CSF rhinorrhoea and when CTC alone fails to identify the site of leakage. Images

Byrne, J V; Ingram, C E; MacVicar, D; Sullivan, F M; Uttley, D

1990-01-01

192

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

PubMed

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

2013-03-31

193

Correlations between P300 components and neurotransmitters in the cerebrospinal fluid.  

PubMed

P300 and cerebrospinal fluid neurotransmitter metabolites and amino acids were examined in 10 patients with Alzheimer's disease, 9 patients with vascular dementia and 10 healthy controls. A negative correlation between P300 amplitude and MHPG concentration, negative correlation between P200 and N200 latencies and norepinephrine concentration, positive correlation between N200 latency and lysine concentration and positive correlation between N100 amplitude and tyrosine concentration were statistically significant. These findings suggest that the noradrenergic system influences P300 amplitude, and that multiple systems may influence P300 components. PMID:9472419

Mochizuki, Y; Oishi, M; Takasu, T

1998-01-01

194

Extremely elevated cerebrospinal fluid protein levels in a child with neurologic symptoms: beware of haemophagocytic lymphohistiocytosis.  

PubMed

Neurologic symptoms can be the initial manifestation of haemophagocytic lymphohistiocytosis (HLH). In this case study, we present a 3-year old boy with a clinical picture of encephalitis, a cerebrospinal fluid (CSF) protein level up to 1165 mg/dl and diffuse cerebral MRI abnormalities. The diagnosis of HLH was established only 6 weeks after initial presentation. The boy recovered after HLH therapy with persisting mild cognitive defects. Genetic investigation demonstrated X-linked lymphoproliferative disease (XLP) as the underlying cause of HLH. The extremely elevated protein level in CSF in this case has not yet been reported in patients with HLH. PMID:24433830

Voeten, Michiel; Maes, Philip; Wojciechowski, Marek; Vandenbossche, Luc; Meyts, Isabelle; Ceulemans, Berten

2014-05-01

195

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.

2011-01-01

196

A Case of Effective Cerebrospinal Fluid Drainage for Paraplegia Caused by Acute Aortic Dissection  

PubMed Central

A 65-year-old man with sudden back pain was transferred to our hospital by ambulance, who also complained of sensory and motor disorder of bilateral legs on arrival. The neurological disorder was gradually aggravated and paraplegia below the level of Th10 was manifested. Computed tomography demonstrated DeBakey IIIb acute aortic dissection; therefore, the paraplegia was thought to be due to spinal cord ischemia caused by the acute aortic dissection. Emergent cerebrospinal fluid drainage was performed, and it was very effective for the relief from paraplegia. The hospital course after the drainage was uneventful and he was discharged on the 39th day after the onset of symptoms.

Hayatsu, Yukihiro; Nagaya, Koichi; Sakuma, Kei; Nagamine, Susumu

2011-01-01

197

Cerebrospinal fluid CXCL13 is a prognostic marker for aseptic meningitis.  

PubMed

In exceptional cases, patients with aseptic meningitis eventually develop aseptic meningoencephalitis. To find a candidate marker for the development of aseptic meningoencephalitis in adult patients diagnosed with aseptic meningitis, we compared 12 different cytokines/chemokines in cerebrospinal fluid (CSF) from 5 patients with aseptic meningoencephalitis, 8 patients with aseptic meningitis, and 8 patients with control disease. Only the CXCL13 concentration was significantly elevated in the CSF of the group with aseptic meningoencephalitis compared with the group with aseptic meningitis. Thus, CSF CXCL13 may be a useful marker for predicting the prognosis of aseptic meningitis. PMID:24907903

Fujimori, Juichi; Nakashima, Ichiro; Kuroda, Hiroshi; Fujihara, Kazuo; Aoki, Masashi

2014-08-15

198

[Electrolyte composition of the cerebrospinal fluid and neuromuscular excitability in epilepsy].  

PubMed

Clinical (Chvostek symptom and Trousseau-Bonsdorf test) and electromyographical investigations of the neuromuscular excitability were performed in patients with different forms of epilepsy. Ionized Ca, Na, K, Cl, and total Mg were measured in the cerebrospinal fluid (CSF). Seventy-five percent of the patients showed clinical and electromyographic signs of the tetanic syndrome. In patients with general seizures the CSF ionized Ca content was decreased as related to that of normal subjects. Brain and neuromuscular excitability increase was related with the shifts in Ca metabolism. PMID:3188753

Ve?n, A M; Biniaurishvili, R G; Masteropulo, A P; Ba?dauletov, I O; Estrov, V G

1988-01-01

199

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.

1996-09-01

200

Age-associated changes of cerebrospinal fluid amyloid-? and tau in cynomolgus monkeys.  

PubMed

Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop ?-amyloid (A?) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associated changes in A? and tau protein in cerebrospinal fluid. The present study was an attempt to specifically address these issues. Cerebrospinal fluid levels of A? and phosphorylated tau were measured in 37 and 22 cynomolgus monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from the present study revealed significant age-associated declines in A?42 levels but not in A?40 and phosphorylated tau levels. This finding appears to parallel changes seen with human aging, in which decreased levels of A?42 can be seen in normal older adults, and supporting that cynomolgus monkeys would be a useful model for studying age-related neurologic disorders associated with Alzheimer-like cerebral proteopathy. PMID:24581480

Yue, Feng; Lu, Chunling; Ai, Yi; Chan, Piu; Zhang, Zhiming

2014-07-01

201

Multicommutated flow analysis system for determination of total protein in cerebrospinal fluid.  

PubMed

A fully mechanized, computer-controlled, multicommutated flow analysis (MCFA) system dedicated for total protein determination in cerebrospinal fluid samples has been developed. For the protein determination the Exton method has been applied. Dedicated turbidimetric and nephelometric flow-through detectors operating according to paired-emitter detector diode principle have been fabricated by integration of two or three respective light emitting diodes. The developed MCFA system is characterized by robust, compact design and low consumption of the sample (72?L). The limits of detection for turbidimetric and nephelometric detection mode are 65mgL(-1) and 9mgL(-1), respectively. For turbidimetric measurements the range of linear response offered by the MCFA system is 72-900mgL(-1), whereas in the case of nephelometric detection 18-500mgL(-1) linear range is obtained. The throughput of the MCFA system is over 30 injection per hour. The analytical system was optimized with bovine serum albumin standards and successfully validated with real samples of human cerebrospinal fluid. PMID:25059127

Strzelak, Kamil; Wi?niewska, Agnieszka; Bobilewicz, Dagna; Koncki, Robert

2014-10-01

202

Noninvasive cerebrospinal fluid shunt flow measurement by Doppler ultrasound using ultrasonically excited bubbles: a feasibility study.  

PubMed

Because normal cerebrospinal fluid (CSF) has almost no natural Doppler scatterers, patency testing of ventriculoperitoneal cerebrospinal fluid shunts (small silastic tubing with lumen diameter of approximately 1 mm draining excessive CSF from the brain) cannot be performed by Doppler ultrasound. We have developed a low-frequency bubble excitation system that generates microbubble scatterers in both distilled water and CSF. Doppler ultrasound can then be used for flow measurement in a ventriculoperitoneal shunt. By using low duty-cycle (approximately 10%), low-frequency (approximately 30 kHz), and low-amplitude (approximately 30 kPa) ultrasound, a population of microbubbles can be maintained for sufficiently long times (>10 min) for Doppler ultrasound measurement, although bubble initiation is inconsistent. The minimum pressure needed for bubble maintenance was found to decrease with increasing burst length and duty cycle. It has been possible to detect the presence of CSF shunt flow down to a mean flow rate of 3 mL/h (mean velocity approximately 0.6 mm/s). The bubble maintenance scheme developed satisfies the safety parameters specified by the American Institute of Ultrasound in Medicine (AIUM) and the US Food and Drug Administration (FDA). Results from both in vitro and in vivo (externalized shunts) experiments indicate the feasibility of this scheme for determining realistic CSF shunt flows, though some practical problems remain before the technique will be ready for clinical use. PMID:10374981

Lam, K W; Drake, J M; Cobbold, R S

1999-03-01

203

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

PubMed Central

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

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

2011-01-01

204

Lipocalin 2 in cerebrospinal fluid as a marker of acute bacterial meningitis  

PubMed Central

Background Early differential diagnosis between acute bacterial and viral meningitis is problematic. We aimed to investigate whether the detection of lipocalin 2, a protein of the acute innate immunity response, may be used as a marker for acute bacterial meningitis. Methods Transgenic mice expressing the human transferrin were infected by intraperitoneal route and were imaged. Cerebrospinal fluid (CSF) was sampled up to 48hours post- infection to measure lipocalin 2. We also tested a collection of 90 and 44 human CSF with confirmed acute bacterial or acute viral meningitis respectively. Results Lipocalin 2 was detected after 5 h in CSF during experimental infection in mice. Lipocalin 2 levels were significantly higher (p?cerebrospinal fluid may discriminate between acute bacterial and viral meningitis in patients with clinical syndrome of meningitis.

2014-01-01

205

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain  

PubMed Central

Background The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. Methods History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg6-Phe7 (MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. Results Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. Conclusions Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia.

Baraniuk, James N; Whalen, Gail; Cunningham, Jill; Clauw, Daniel J

2004-01-01

206

Cerebrospinal Fluid Pharmacology: An Improved Pharmacology Approach for Chinese Herbal Medicine Research  

PubMed Central

Despite many successful applications of Chinese herbal medicine (CHM) in the treatment and prevention of neurological diseases (ND), the fully scientific understanding of CHM's action mechanisms had been hampered for lack of appropriate methods to explore the combinatorial rules, the synergistic mechanisms, and the molecular basis of CHM. As an improved pharmacology approach, cerebrospinal fluid pharmacology (CSFP), based on the fact that cerebrospinal fluid plays an important role in the health maintenance of specific survival environment for neurons and glial cells, has been constructed and applied to CHM research for treating ND. In the present review, the concept and advantages of CSFP are briefly introduced. The approaches and key technologies of CSFP in CHM research are also collated and analyzed. Furthermore, the developing tendency of CSFP is summarized, and its framework in CHM research is also proposed. In summary, CSFP provides a new strategy not only to eliminate some barriers of CHM research for treating ND, but also to broaden the pharmacology research for bridging the gap between CHM and modern medicine. Moreover, the advancements in CSFP will bring about a conceptual move in active ingredients discovery of CHM and make a significant contribution to CHM modernization and globalization.

Wu, Yan-qing; Zhou, Ying-wu; Qin, Xiu-de; Hua, Sheng-yu; Zhang, Yu-lian; Kang, Li-yuan

2013-01-01

207

Characterisation of the pro opiocortin family of peptides in human cerebrospinal fluid.  

PubMed

Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinal fluid. Samples of cerebrospinal fluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing's disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column fractions were assayed for N- and C-terminal beta-lipotropin, N-terminal ACTH and gamma-MSH immunoreactivity. Elution profiles obtained from chromatography on Sephadex G-50 demonstrated peaks of immunoreactivity corresponding to the elution positions of synthetic human beta-endorphin, highly purified beta-lipotropin and highly purified gamma-lipotropin in all CSF samples. A peak of a large molecular weight material with N and C terminal beta-lipotropin immunoreactivity was also detected. Chromatography of CSF on Sephadex G-75 showed this large molecular weight peak to be comprised of peptides eluting in the positions of a 31K molecular weight marker with beta-lipotropin and ACTH immunoreactivity and a 16K molecular weight marker with gamma-MSH immunoreactivity. This suggests the presence of the common precursor to ACTH and LPH in the CSF. PMID:7219672

McLoughlin, L; Lowry, P J; Ratter, S J; Hope, J; Besser, G M; Rees, L H

1981-04-01

208

The amyloid-? oligomer count in cerebrospinal fluid is a biomarker for Alzheimer's disease.  

PubMed

Recent studies indicate that small amyloid-? peptide (A?) oligomers are the major toxic species responsible for development and progression of Alzheimer's disease (AD). Therefore, we suggest that the number of A? oligomers in body fluids is the most direct and relevant biomarker for AD. Determination of the A? oligomer content of cerebrospinal fluid (CSF) samples from 14 AD patients and 12 age-matched controls revealed a clear distinction between both groups. All samples of the control group showed homogenously low numbers of A? oligomers, while the samples of the AD group exhibited significantly higher levels of A? oligomers. The A? oligomer numbers correlated with the patients' Mini-Mental State Examination scores. This indicates that the quantity of A? oligomers in CSF reflects the severity of the disease and that A? oligomers play a crucial role in AD pathology and in turn can be used as a diagnostic biomarker. PMID:23313925

Wang-Dietrich, Lei; Funke, Susanne Aileen; Kühbach, Katja; Wang, Kun; Besmehn, Astrid; Willbold, Sabine; Cinar, Yeliz; Bannach, Oliver; Birkmann, Eva; Willbold, Dieter

2013-01-01

209

Gas Chromatography-Mass Spectrometry-Based Metabolic Profiling of Cerebrospinal Fluid from Epileptic Dogs  

PubMed Central

ABSTRACT Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy.

HASEGAWA, Tetsuya; SUMITA, Maho; HORITANI, Yusuke; TAMAI, Reo; TANAKA, Katsuhiro; KOMORI, Masayuki; TAKENAKA, Shigeo

2013-01-01

210

Cerebrospinal fluid involvement in a case of visceral leishmaniasis associated with hemophagocytic lymphohistiocytosis.  

PubMed

Hemophagocytic Lymphohistiocytosis (HLH) implies a benign generalized histiocytic proliferate with erythrophagocytosis and it includes familial hemophagocytic lymphohistiocytosis and secondary hemophgocytosis. Spinal fluid changes like mild to moderate pleocytosis (most of the cells are lymphocytes and macrophages) and sometimes hemophagocytosis are seen in primary HLH but are not reported in secondary HLH. Here we report a case of a previously healthy 10 months old male infant who was diagnosed as familial HLH with evidence of CSF hemophagocytosis. He was started on the HLH 2004 treatment protocol with no improvement. A second bone marrow aspiration revealed leshmania donovani antibodies and he was started on anti-leishmania treatment with dramatic response.To the best of our knowledge, this is the first case of secondary HLH with evidence of hemophagocytosis in cerebrospinal fluid. PMID:21748112

Fathalla, Mahmoud; Hashim, Javad; Alkindy, Hussein; Wali, Yasser

2007-12-01

211

Cerebrospinal Fluid Involvement in a Case of Visceral Leishmaniasis Associated with Hemophagocytic Lymphohistiocytosis  

PubMed Central

Hemophagocytic Lymphohistiocytosis (HLH) implies a benign generalized histiocytic proliferate with erythrophagocytosis and it includes familial hemophagocytic lymphohistiocytosis and secondary hemophgocytosis. Spinal fluid changes like mild to moderate pleocytosis (most of the cells are lymphocytes and macrophages) and sometimes hemophagocytosis are seen in primary HLH but are not reported in secondary HLH. Here we report a case of a previously healthy 10 months old male infant who was diagnosed as familial HLH with evidence of CSF hemophagocytosis. He was started on the HLH 2004 treatment protocol with no improvement. A second bone marrow aspiration revealed leshmania donovani antibodies and he was started on anti-leishmania treatment with dramatic response.To the best of our knowledge, this is the first case of secondary HLH with evidence of hemophagocytosis in cerebrospinal fluid.

Fathalla, Mahmoud; Hashim, Javad; Alkindy, Hussein; Wali, Yasser

2007-01-01

212

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

PubMed

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

2013-07-01

213

Gas chromatography-mass spectrometry-based metabolic profiling of cerebrospinal fluid from epileptic dogs.  

PubMed

Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy. PMID:24334864

Hasegawa, Tetsuya; Sumita, Maho; Horitani, Yusuke; Tamai, Reo; Tanaka, Katsuhiro; Komori, Masayuki; Takenaka, Shigeo

2014-04-01

214

The role of cerebrospinal fluid pressure in glaucoma and other ophthalmic diseases: A review  

PubMed Central

Glaucoma is one of the most common causes of blindness in the world. Well-known risk factors include age, race, a positive family history and elevated intraocular pressures. A newly proposed risk factor is decreased cerebrospinal fluid pressure (CSFP). This concept is based on the notion that a pressure differential exists across the lamina cribrosa, which separates the intraocular space from the subarachnoid fluid space. In this construct, an increased translaminar pressure difference will occur with a relative increase in elevated intraocular pressure or a reduction in CSFP. This net change in pressure is proposed to act on the tissues within the optic nerve head, potentially contributing to glaucomatous optic neuropathy. Similarly, patients with ocular hypertension who have elevated CSFPs, would enjoy a relatively protective effect from glaucomatous damage. This review will focus on the current literature pertaining to the role of CSFP in glaucoma. Additionally, the authors examine the relationship between glaucoma and other known CSFP-related ophthalmic disorders.

Fleischman, David; Allingham, R. Rand

2013-01-01

215

A semi-quantitative ELISA for detection of Trypanosoma brucei gambiense specific antibodies in serum and cerebrospinal fluid of sleeping sickness patients  

Microsoft Academic Search

A semi-quantitative ELISA, using variable surface glycoprotein of T.b. gambiense as antigen, was developed for the detection of antibodies of different immunoglobulin isotypes in serum and cerebrospinal fluid of sleeping sickness patients. Using the assay, the antibody profiles of paired serum and cerebrospinal fluid samples of 28 patients have been studied. Total concentrations of various Ig isotypes were determined as

V Lejon; P Büscher; E Magnus; A Moons; I Wouters; N Van Meirvenne

1998-01-01

216

Physical characteristics in the new model of the cerebrospinal fluid system.  

PubMed

It is unknown which factors determine the changes in cerebrospinal fluid (CSF) pressure inside the craniospinal system during the changes of the body position. To test this, we have developed a new model of the CSF system, which by its biophysical characteristics and dimensions imitates the CSF system in cats. The results obtained on a model were compared to those in animals observed during changes of body position. A new model was constructed from two parts with different physical characteristics. The "cranial" part is developed from a plastic tube with unchangeable volume, while the "spinal" part is made of a rubber baloon, with modulus of elasticity similar to that of animal spinal dura. In upright position, in the "cranial" part of the model the negative pressure appears without any measurable changes in the fluid volume, while in "spinal" part the fluid pressure is positive. All of the observed changes are in accordance to the law of the fluid mechanics. Alterations of the CSF pressure in cats during the changes of the body position are not significantly different compared to those observed on our new model. This suggests that the CSF pressure changes are related to the fluid mechanics, and do not depend on CSF secretion and circulation. It seems that in all body positions the cranial volume of blood and CSF remains constant, which enables a good blood brain perfusion. PMID:21648311

Jurjevi?, Ivana; Rados, Milan; Oreskovi?, Janko; Priji?, Radovan; Tvrdei?, Ante; Klarica, Marijan

2011-01-01

217

Cerebrospinal fluid MicroRNA profiling using quantitative real time PCR.  

PubMed

MicroRNAs (miRNAs) constitute a potent layer of gene regulation by guiding RISC to target sites located on mRNAs and, consequently, by modulating their translational repression. Changes in miRNA expression have been shown to be involved in the development of all major complex diseases. Furthermore, recent findings showed that miRNAs can be secreted to the extracellular environment and enter the bloodstream and other body fluids where they can circulate with high stability. The function of such circulating miRNAs remains largely elusive, but systematic high throughput approaches, such as miRNA profiling arrays, have lead to the identification of miRNA signatures in several pathological conditions, including neurodegenerative disorders and several types of cancers. In this context, the identification of miRNA expression profile in the cerebrospinal fluid, as reported in our recent study, makes miRNAs attractive candidates for biomarker analysis. There are several tools available for profiling microRNAs, such as microarrays, quantitative real-time PCR (qPCR), and deep sequencing. Here, we describe a sensitive method to profile microRNAs in cerebrospinal fluids by quantitative real-time PCR. We used the Exiqon microRNA ready-to-use PCR human panels I and II V2.R, which allows detection of 742 unique human microRNAs. We performed the arrays in triplicate runs and we processed and analyzed data using the GenEx Professional 5 software. Using this protocol, we have successfully profiled microRNAs in various types of cell lines and primary cells, CSF, plasma, and formalin-fixed paraffin-embedded tissues. PMID:24514260

Pacifici, Marco; Delbue, Serena; Kadri, Ferdous; Peruzzi, Francesca

2014-01-01

218

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

PubMed

Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. PMID:24745469

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

2014-07-30

219

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

2004-01-01

220

Interleukin6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes  

Microsoft Academic Search

Cytokines are involved in nerve regeneration by modulating the synthesis of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigated by monitoring the release of IL-6 and NGF in ventricular cerebrospinal fluid (CSF) of 22 patients with severe traumatic brain injuries. IL-6 was found in the CSF of all individuals

Thomas Kossmann; Volkmar Hans; Hans-Georg Imhof; Otmar Trentz; Maria Cristina Morganti-Kossmann

1996-01-01

221

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

2009-01-01

222

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

2008-01-01

223

Cathepsin B and H activities and cystatin C concentrations in cerebrospinal fluid from patients with leptomeningeal metastasis  

Microsoft Academic Search

Background: Cysteine proteases are involved in the extension of cancer into the subarachnoid space. The presence of cathepsins B and H along with their potent inhibitor cystatin C in the cerebrospinal fluid (CSF) was investigated in patients with leptomeningeal metastasis of cancer (LM). Materials and methods: CSF samples were obtained in 16 cases of LM (10 solid tumors and 6

Atsushi Nagai; Masaharu Terashima; Takayuki Harada; Koichi Shimode; Hiromi Takeuchi; Yohko Murakawa; Makoto Nagasaki; Akinobu Nakano; Shotai Kobayashi

2003-01-01

224

FACS analysis—a new and accurate tool in the diagnosis of lymphoma in the cerebrospinal fluid  

Microsoft Academic Search

Background: Fluorescence activated cell scanning (FACS) is a useful tool for identifying malignant cell clones of lymphoma cells in cerebrospinal fluid (CSF) by immunological phenotype. Methods: We used FACS analysis for demonstrating it to be a quick and reliable technology that is available in most hematological laboratories. In this study, we demonstrate the clinical application of FACS analysis within a

Sabine Urbanits; Andrea Griesmacher; Georg Hopfinger; Günther Stockhammer; Alireza Karimi; Mathias M. Müller; Elisabeth Pittermann; Wolfgang Grisold

2002-01-01

225

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

2006-01-01

226

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

2004-01-01

227

Detection of Neisseria meningitidis from negative blood cultures and cerebrospinal fluid with the FilmArray blood culture identification panel.  

PubMed

The FilmArray blood culture identification (BCID) panel is a rapid molecular diagnostic test approved for use with positive blood culture material. We describe a fatal case of meningococcemia with central nervous system (CNS) involvement detected using the BCID test with culture-negative blood and cerebrospinal fluid. PMID:24740076

Pardo, Joe; Klinker, Kenneth P; Borgert, Samuel J; Butler, Brittany M; Rand, Kenneth H; Iovine, Nicole M

2014-06-01

228

Cerebrospinal Fluid Pressure, Growth, and Hematology in Relation to Retinol Status of the Rat in Acute Vitamin A Deficiency  

Microsoft Academic Search

In order to produce a model with which to isolate the primary changes associated with vitamin A deficiency in the weanling rat, cerebrospinal fluid (CSF) pressure, body weight gain, and hématologie responses were charac terized in two experiments. In experiment 1, 35 weanling male rats were fed graded intakes of vitamin A for a 5-week comparison method. It was predicted

JOYCE E. COREY; ANDK. C. HAYES

229

Herpes simplex virus specific antibody determined by immunoblotting in cerebrospinal fluid of a patient with the Guillain-Barr? syndrome.  

PubMed Central

The Guillain-Barré syndrome is often preceded by a herpes virus infection. Herpes simplex virus, however, has rarely been observed as the causative agent. A patient is described with a herpes simplex virus infection followed by a Guillain-Barré syndrome. Immunoblotting was used to detect herpes simplex virus-specific antibodies in serum and cerebrospinal fluid. Images

Bernsen, H J; Van Loon, A M; Poels, R F; Verhagen, W I; Frenken, C W

1989-01-01

230

Cytological and immunoglobulin findings in cerebrospinal fluid of symptomatic and asymptomatic human immunodeficiency virus (HIV) seropositive patients  

Microsoft Academic Search

Summary Immunostimulation in the central nervous system (CNS) measured as abnormal intrathecal immunoglobulin production or activated lymphocytes in the cerebrospinal fluid (CSF), was found in 22 of 25 HIV seropositive patients. All of 11 patients with symptomatic HIV infection and nine of 14 asymptomatic patients had an increased IgG index or a Tourtellotte's production number indicating CNS infection. The amount

L. Hagberg; G. Norkrans; A. Forsman; E. Rybo; L. Svennerholm

1988-01-01

231

DETECTION OF LIGHT SUBUNIT NEUROFILAMENT AND GLIAL FIBRILLARY ACIDIC PROTEIN IN CEREBROSPINAL FLUID OFTRYPANOSOMA BRUCEI GAMBIENSE-INFECTED PATIENTS  

Microsoft Academic Search

Light subunit neurofilament (NFL) and glial fibrillary acidic protein (GFAP) concentrations were de- termined in cerebrospinal fluid (CSF) of 34 patients with human African trypanosomiasis (HAT), five serologically positive but parasitologically unconfirmed individuals, and four healthy controls without evidence of HAT. In patients with second stage HAT (n 5 30), NFL levels were abnormally elevated in 10 cases and GFAP

V. LEJON; L. E. ROSENGREN; P. BUSCHER; J.-E. KARLSSON; H. N. SEMA

1999-01-01

232

Blood–cerebrospinal fluid barrier and intrathecal immunoglobulins compared to field diagnosis of central nervous system involvement in sleeping sickness  

Microsoft Academic Search

Diagnosis of central nervous system (CNS) involvement in sleeping sickness is crucial in order to give an appropriate treatment regimen. Neurological symptoms occur late, therefore field diagnosis is based on white blood cell count, total protein concentration and presence of trypanosomes in cerebrospinal fluid (CSF). More sensitive and specific parameters are now available. Blood–CSF barrier (B-CSFB) dysfunction, intrathecal total and

P. M Preux; A Stanghellini; M. O Jauberteau; P Büscher; M Dumas

2002-01-01

233

An Age-Related Correlation between Levels of ?-Amyloid Precursor Protein and ?-Amyloid in Human Cerebrospinal Fluid  

Microsoft Academic Search

We investigated the levels of amyloid precursor protein (APP) and ?-amyloid peptide (A?) in the cerebrospinal fluid (CSF) from 110 individuals ranging in age from newborn to 82-years old to analyze their regulation with age. These samples were segregated into two groups; one group contained CSF samples from patients with diagnosed CNS abnormalities and the second group contained CSF samples

R. T. Carroll; M. R. Lust; K. S. Kim; P. D. Doyle; M. R. Emmerling

1995-01-01

234

Progression to Neuropsychological Impairment in Human Immunodeficiency Virus Infection Predicted by Elevated Cerebrospinal Fluid Levels of Human Immunodeficiency Virus RNA  

Microsoft Academic Search

Background: If cerebrospinal fluid (CSF) human im- munodeficiency virus (HIV) RNA levels are elevated be- fore the development of neuropsychological (NP) im- pairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeu- tic interventions designed to lower CSF HIV levels. Objective: To determine whether increased CSF HIV RNA levels at an earlier time

Ronald J. Ellis; David J. Moore; Meredith E. Childers; Scott Letendre; J. Allen McCutchan; Tanya Wolfson; Stephen A. Spector; Karen Hsia; Robert K. Heaton; Igor Grant

2002-01-01

235

Bone marrow elements in cerebrospinal fluid: Review of literature with a case study  

PubMed Central

Presence of bone marrow elements in cerebrospinal fluid is rare. Journal publications on this topic are few and majority of them were written over a decade ago mostly as case reports in young children or the elderly. The increased cellularity and presence of myeloid precursors can be a pitfall and may be misdiagnosed as leukemia or lymphoma or central nervous system infection, when the specimen is actually not representative. With the intention to create awareness of potential pitfalls and avoid erroneous diagnoses, as well as adding on to the current photo archive of bone marrow elements in CSF, we present a recent case of bone marrow contaminants in the CSF of a 16-year-old girl.

Thomas, Anitha Ann; Goh, Felicia Tze Yee

2013-01-01

236

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

PubMed

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

2011-09-01

237

Cerebrospinal fluid as a reflector of central cholinergic and amino acid neurotransmitter activity in cerebellar ataxia.  

PubMed

Cerebrospinal fluid (CSF) amino acid neurotransmitters, related compounds, and their precursors, choline levels, and acetylcholinesterase activity were measured in the CSF of patients with cerebellar ataxia during a randomized, double-blind, crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were significantly lower in patients with cerebellar ataxia compared with controls. Physostigmine selectively reduced the level of CSF isoleucine and elevated the levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase activity and in the levels of plasma amino compounds in patients with cerebellar ataxia when compared with controls. Median ataxia scores did not statistically differ between placebo and physostigmine nor did functional improvement occur in any of the patients. PMID:1978660

Manyam, B V; Giacobini, E; Ferraro, T N; Hare, T A

1990-11-01

238

Trace element studies on whole human cerebrospinal fluid with external beam PIXE.  

PubMed

External beam PIXE analysis with a 2.4 MeV proton beam was used to determine the concentrations of K, Ca, Fe, Cu, Zn and Br in cerebrospinal fluid from patients having various disorders. The obtained total concentration ranges K 34,000-1,079,000, Ca 5300-81,300, Fe 40-1030, Cu 20-1650, Zn 15-1250 and Br 400-43,000 micrograms/kg are compared with the values given in the literature. In certain patients there were very high CSF bromine levels, but this was shown to be the result of taking medications presented as bromide salts. The possibility of using the method in clinical practice for CSF analysis is considered. The new method of preparing self-supporting films of the samples was used. This method was further optimized by investigating in detail the use of EDTA as a homogenizer. PMID:2980812

Lapatto, R; Hyvönen-Dabek, M; Dabek, J T; Räisänen, J

1988-09-01

239

Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy.  

PubMed

Proteomic analysis of cerebrospinal fluid (CSF) from patients with temporal lobe epilepsy (TLE) and controls was carried out using two-dimensional gel electrophoresis followed by liquid chromatography electrospray ionization tandem mass spectrometry. Five protein spots showed significant differential expression (p<0.05): vitamin D-binding protein (DBP) was elevated in the CSF of TLE patients whereas cathepsin D, apolipoprotein J, Fam3c, and superoxide dismutase 1 (SOD1) were decreased in the CSF of TLE patients. Additional six protein spots presented only in the CSF of epilepsy patients were identified as tetranectin (TN), talin-2, apolipoprotein E, immunoglobulin lambda light chain (IGL@), immunoglobulin kappa variable light chain 1-5 (IGKV1-5), and procollagen C-endopeptidase enhancer 1 (PCOLCE). Expression of DBP, SOD1 and talin-2 was validated by western blot. Our results may provide better understanding of the pathophysiologic mechanisms underlying epileptogenesis and possible epilepsy biomarkers. PMID:19109932

Xiao, Fei; Chen, Dan; Lu, Yang; Xiao, Zheng; Guan, Li-feng; Yuan, Jie; Wang, Liang; Xi, Zhi-qin; Wang, Xue-feng

2009-02-19

240

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

2012-01-01

241

Hepatocyte growth factor levels in cerebrospinal fluid: a comparison between acute bacterial and nonbacterial meningitis.  

PubMed

The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P<.001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis. PMID:10837201

Nayeri, F; Nilsson, I; Hagberg, L; Brudin, L; Roberg, M; Söderström, C; Forsberg, P

2000-06-01

242

Analysis of cerebrospinal fluid from field cases of some common ovine neurological diseases.  

PubMed

Analysis of cerebrospinal fluid (CSF) samples from normal sheep and from cases of some common neurological diseases revealed a significant increase (P less than 0.05) in the group mean CSF protein concentration for meningitis, listeriosis and spinal abscess but not for scrapie, spinal injury, ovine pregnancy toxaemia or polioencephalomalacia. The CSF white blood cell count (WBC) was significantly increased (P less than 0.05) in the meningitis group and in those cases of listeriosis which failed to respond to antibiotic therapy. All cases of bacterial infection of the central nervous system (CNS) could be identified by the combined interpretation of the protein concentration and the differential WBC count. It is concluded that CSF analysis is useful clinically in differentiating traumatic from infective spinal lesions and toxic or metabolic lesions from bacterial meningitis in sheep. PMID:1551009

Scott, P R

1992-01-01

243

Oligoclonal bands in cerebrospinal fluid detected by PhastSystem isoelectric focusing.  

PubMed

Pharmacia's "PhastSystem" for semi-automated isoelectric focusing (IEF) in thin precast polyacrylamide gels (PAGE) was found to be as sensitive as high-resolution protein electrophoresis (HRPE) in agarose gels and conventional PAGE-IEF for detection of oligoclonal banding (OB) in concentrated cerebrospinal fluid (CSF) samples. Both PhastSystem IEF and HRPE revealed OB in CSF from eight of nine multiple sclerosis patients and four of 10 patients with various types of infection of the central nervous system as opposed to only two of 70 patients with miscellaneous neuropsychiatric disorders. The PhastSystem also frequently detected OB in silver-stained, unconcentrated CSF from patients with multiple sclerosis. PMID:1688744

Wybo, I; Van Blerk, M; Malfait, R; Goubert, P; Gorus, F

1990-01-01

244

Higher cerebrospinal fluid homovanillic acid levels in depressed patients with comorbid posttraumatic stress disorder.  

PubMed

Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects with a current MDE and comorbid PTSD, and healthy volunteers. Depressed subjects with comorbid PTSD had higher CSF homovanillic acid (HVA) levels compared with depressed subjects without comorbid PTSD or healthy volunteers. Higher HVA was present after adjustment for sex, lifetime aggression severity and depression scores, alcoholism, tobacco smoking, comorbid cluster B personality disorder, reported childhood abuse, and psychosis. We found no group difference in CSF 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels. Higher dopaminergic activity may contribute to alterations in memory and other cognitive functions, anhedonia, and hypervigilance observed in PTSD. PMID:15695066

Sher, Leo; Oquendo, Maria A; Li, Shuhua; Burke, Ainsley K; Grunebaum, Michael F; Zalsman, Gil; Huang, Yung-yu; Mann, J John

2005-03-01

245

Detection and genotyping of enteroviruses in cerebrospinal fluid in patients in Victoria, Australia, 2007-2013.  

PubMed

Genotyping by VP1 fragment polymerase chain reaction (PCR) and nucleic acid sequencing to detect enterovirus (EV) genotypes was performed directly on 729 EV PCR positive cerebrospinal fluid (CSF) samples collected between 2007 and 2012 from Victorian hospital inpatients. The overall genotype identification rate from CSF-positive material was 43%. The four most common genotypes identified were Echovirus 6 (24%), Echovirus 30 (17%), Echovirus 25 (10%), and Coxsackievirus A9 (10%), together comprising 61% of all EVs typed. The seasonal distribution of all EVs identified followed the recognized pattern of mainly summer epidemics. Three of the four predominant genotypes were present in each of the 6 years in which the study was conducted, with 20 other EV genotypes also detected, often in only a single year. Genotyping of EVs directly in CSF is faster, simpler and more sensitive than traditional virus neutralization assays performed on EV positive samples. J. Med. Virol. 86:1609-1613, 2014. © 2014 Wiley Periodicals, Inc. PMID:24474149

Papadakis, Georgina; Chibo, Doris; Druce, Julian; Catton, Michael; Birch, Chris

2014-09-01

246

Characterization of clinically significant isolates of Staphylococcus epidermidis from patients with cerebrospinal fluid shunt infections.  

PubMed Central

Biotyping, slime production, antibiograms, extrachromosomal DNA banding and total DNA restriction analysis were used to characterize Staphylococcus epidermidis strains causing cerebrospinal fluid shunt infections in 11 patients. Infections considered to be community acquired and those acquired in the first 2 weeks of hospital admission were due to oxacillin-susceptible isolates. Multiply resistant strains were isolated from patients who were in hospital for more than 1 month before tube implantation. Slime was detected in staphylococci for 54% of cases, but its expression varied. Strains from different patients could be differentiated from one another by the extrachromosomal DNA bandings and total DNA restriction patterns, but isolates from the same patient were usually similar. During the period of external drainage, epidemiological markers were useful in differentiating persistence of infection from contamination or re-infection by a new strain. Images Fig. 1

Etienne, J.; Charpin, B.; Grando, J.; Brun, Y.; Bes, M.; Fleurette, J.

1991-01-01

247

Brain, skull, and cerebrospinal fluid volumes in adult posttraumatic stress disorder.  

PubMed

Children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) exhibit smaller intracranial tissue volume than controls. Linear relationships have also been observed between intracranial tissue volume and the age of maltreatment onset. The authors explored associations among adult PTSD, early trauma, and cerebral volumes in 99 combat veterans. A bone-based estimate of cranial volume was developed to adjust for variation in body size. Posttraumatic stress disorder was not associated with smaller cerebral tissue volume, but rather with smaller cerebrospinal fluid (CSF) and cranial volumes. These findings co-occurred with expected effects of alcoholism and aging on cerebral tissue and CSF volumes. The results point to early developmental divergences between groups with and without PTSD following adult trauma. PMID:17955544

Woodward, Steven H; Kaloupek, Danny G; Streeter, Chris C; Kimble, Matthew O; Reiss, Allan L; Eliez, Stephan; Wald, Lawrence L; Renshaw, Perry F; Frederick, Blaise B; Lane, Barton; Sheikh, Javaid I; Stegman, Wendy K; Kutter, Catherine J; Stewart, Lorraine P; Prestel, Rebecca S; Arsenault, Ned J

2007-10-01

248

Low Raltegravir Concentration in Cerebrospinal Fluid in Patients With ABCG2 Genetic Variants.  

PubMed

: Adenosine triphosphate-binding cassette transporter G2 (ABCG2) is expressed on the cerebrospinal fluid (CSF) side of choroid plexus epithelial cells, which form the blood-CSF barrier. Raltegravir was recently identified as a substrate of ABCG2. In the present study, we analyzed the relationship between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and raltegravir concentrations in 31 plasma and 14 CSF samples of HIV-infected patients treated with raltegravir-containing regimens. The mean CSF raltegravir concentration was significantly lower in CA (25.5 ng/mL) and AA (<10 ng/mL) genotypes at position 421 in ABCG2 gene compared with CC (103.6 ng/mL) genotype holders (P = 0.016). PMID:24872134

Tsuchiya, Kiyoto; Hayashida, Tsunefusa; Hamada, Akinobu; Kato, Shingo; Oka, Shinichi; Gatanaga, Hiroyuki

2014-08-15

249

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

PubMed

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

2013-07-01

250

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

2011-01-01

251

Leptomeningeal gliomatosis with high levels of adenosine deaminase in the cerebrospinal fluid.  

PubMed

A 61-year-old man developed disturbance of consciousness for 2 weeks. He showed neck stiffness and hyporeflexia. Analysis of his cerebrospinal fluid (CSF) revealed pleocytosis and markedly reduced glucose contents. Adenosine deaminase (ADA) levels in the CSF were elevated (28.8 IU/l). Brain magnetic resonance imagings showed enhancement of the leptomeninges. Tuberculous meningitis was considered, but antituberculous drug was not effective. Repeated cytological analysis of the CSF demonstrated atypical cells with enlarged unevenly distributed nuclei and immunoreactive with glial fibrillary acidic protein. We diagnosed him as leptomeningeal gliomatosis. CSF ADA may be elevated in this rare disorder, and here we emphasize that repeated cytological analysis with immunohistochemical staining was useful for diagnosis. PMID:24807273

Nishihara, Hideaki; Omoto, Masatoshi; Ogasawara, Jun-Ichi; Koga, Michiaki; Kawai, Motoharu; Kanda, Takashi

2014-01-01

252

Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts.  

PubMed

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The effects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances. PMID:11124792

Carrion, E; Hertzog, J H; Medlock, M D; Hauser, G J; Dalton, H J

2001-01-01

253

Repair of spontaneous cerebrospinal fluid otorrhea from defect of middle cranial fossa.  

PubMed

Spontaneous cerebrospinal fluid (CSF) otorrhea is defined as CSF otorrhea where there are no identifiable causes including previous trauma, surgery, infection, neoplasm or congenital anomaly. The condition is rare. The origin of CSF leak is commonly a defect in the tegmen of the middle cranial fossa. The pathophysiology of spontaneous CSF otorrhea is unclear. Two theories of the etiology of bony defects of the temporal bone are the congenital bony defect theory and arachnoid granulation theory. The authors experienced a case of a 49-year-old female patient admitted with the complaint of persistent right ear fullness. Computed tomography revealed a large defect of the middle fossa and suspicious CSF otorrhea through the defect of tegmen tympani. Repair was successful with multiple bone chips using the transmastoid approach. The postoperative course was good and there has been no recurrence of the CSF leakage. PMID:24653924

Boo, Sung Hyun; Goh, Young Bum; Han, Chi-Sung

2013-12-01

254

The Choroid Plexus and Cerebrospinal Fluid: Emerging Roles in Development, Disease, and Therapy  

PubMed Central

Although universally recognized as the source of cerebrospinal fluid (CSF), the choroid plexus (ChP) has been one of the most understudied tissues in neuroscience. The reasons for this are multiple and varied, including historical perceptions about passive and permissive roles for the ChP, experimental issues, and lack of clinical salience. However, recent work on the ChP and instructive signals in the CSF have sparked new hypotheses about how the ChP and CSF provide unexpected means for regulating nervous system structure and function in health and disease, as well as new ChP-based therapeutic approaches using pluripotent stem cell technology. This minisymposium combines new and established investigators to capture some of the newfound excitement surrounding the ChP-CSF system.

Bjornsson, Christopher S.; Dymecki, Susan M.; Gilbertson, Richard J.; Holtzman, David M.

2013-01-01

255

Gold nanoparticle-based immuno-PCR for detection of tau protein in cerebrospinal fluid.  

PubMed

Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and some other brain diseases. Enzyme-linked immunosorbent assays (ELISAs) have been mostly used for quantification of tau and other biomarkers in CSF. However, these assays do not have sufficient sensitivity and dynamic range. In this study we tested the suitability of gold nanoparticles functionalized with tau-specific monoclonal antibody and oligonucleotide template for immuno-polymerase chain reaction (Nano-iPCR) quantification of tau protein in human CSF samples and compared it with ELISA, either commercial or newly developed with tyramide signal amplification. Our data indicate that Nano-iPCR is superior in sensitivity and detection range to ELISA in tau protein detection. PMID:24642424

Stegurová, Lucie; Dráberová, Eduarda; Bartos, Ales; Dráber, Pavel; Rípová, Daniela; Dráber, Petr

2014-04-01

256

Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin  

NASA Technical Reports Server (NTRS)

Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

Morrow, B. A.; Keil, L. C.; Severs, W. B.

1992-01-01

257

Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa pressure.  

PubMed

Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSF-P), has been investigated as a possible risk factor in glaucoma pathogenesis. In fact, lower CSF-P in the setting of normal IOP has been implicated as a potential risk factor for normal tension glaucoma. Increased TLCPD has been associated with decreased neuroretinal rim area and increased visual field defects. Furthermore, dysregulation of systemic blood pressure has been associated with changes in IOP. Recent studies have also suggested that increased body mass index (BMI) is associated with decreased prevalence of glaucoma, which may be due to an increased CSF-P with increased BMI found in many studies. Given the interaction of various pressures, their role in glaucoma pathophysiology has come under investigation and warrants further study in order to better understand the aetiology and progression of glaucoma. PMID:24307714

Marek, Brian; Harris, Alon; Kanakamedala, Priyanka; Lee, Eric; Amireskandari, Annahita; Carichino, Lucia; Guidoboni, Giovanna; Tobe, Leslie Abrams; Siesky, Brent

2014-06-01

258

A case of effective cerebrospinal fluid drainage for paraplegia caused by acute aortic dissection.  

PubMed

A 65-year-old man with sudden back pain was transferred to our hospital by ambulance, who also complained of sensory and motor disorder of bilateral legs on arrival. The neurological disorder was gradually aggravated and paraplegia below the level of Th10 was manifested. Computed tomography demonstrated DeBakey IIIb acute aortic dissection; therefore, the paraplegia was thought to be due to spinal cord ischemia caused by the acute aortic dissection. Emergent cerebrospinal fluid drainage was performed, and it was very effective for the relief from paraplegia. The hospital course after the drainage was uneventful and he was discharged on the 39th day after the onset of symptoms. PMID:23555433

Hayatsu, Yukihiro; Nagaya, Koichi; Sakuma, Kei; Nagamine, Susumu

2011-01-01

259

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.

2013-01-01

260

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.

2013-01-01

261

[Importance of urgent cerebrospinal fluid examination for early diagnosis of central nervous system infections].  

PubMed

To a certain extent, the cerebrospinal fluid (CSF) composition reflects the current status of the central nervous system (CNS). Therefore, studying changes in even the most essential CSF parameters provides enormous scope for obtaining valuable information about processes in the CNS in relation to its disorders. The article aims at presenting our current conception of urgent CSF examination with special emphasis on early diagnosis of central nervous infections. In particular, the focus is on evaluating energy conditions in the CSF compartment and permeability of the blood-brain and blood-CSF barriers, CSF cytology, detecting CNS tissue destruction and bleeding into CNS pathways and monitoring the levels of systemic inflammatory activity. PMID:17417750

Kelbich, Petr; Koudelková, Martina; Machová, Hana; Tomaskovic, Miloslav; Vachata, Petr; Kotalíková, Patricie; Chmelíková, Vlasta; Hanuljaková, Eva

2007-02-01

262

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

PubMed

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

2013-07-01

263

Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness  

NASA Technical Reports Server (NTRS)

The cerebrospinal fluid drawn from the fourth ventricles of the brains of cats during and after the development of motion sickness was studied to determine what neurotransmitters may be involved in the development of the sickness. The analytical procedure, which uses HPLC coupled with n-electrode coulometric electrochemical detection to measure many compounds with picogram sensitivity, is described. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA, and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not. None of the total of 36 identified compounds identified in the samples varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

Lucot, James B.; Crampton, George H.; Matson, Wayne R.; Gamache, Paul H.

1989-01-01

264

Cerebrospinal Fluid from Alzheimer's disease patients promotes amyloid beta-protein oligomerization.  

PubMed

Oligomers of the amyloid beta-protein (Abeta) play an important role in Alzheimer's disease (AD). We hypothesized that AD patients have a central nervous system environment that promotes Abeta oligomerization. We investigated the effect of cerebrospinal fluid (CSF) from 33 patients with AD and 33 age-matched, non-demented controls on oligomerization of Abeta1-40 and Abeta1-42 using the technique of photo-induced cross-linking of unmodified proteins. CSF inhibited oligomerization of both Abeta1-40 and Abeta1-42. This inhibitory effect was significantly weaker in AD patients than in non-demented controls. Our results indicate that AD patients have a CSF environment favorable for Abeta oligomerization. PMID:20413863

Ikeda, Tokuhei; Ono, Kenjiro; Elashoff, David; Condron, Margaret M; Noguchi-Shinohara, Moeko; Yoshita, Mitsuhiro; Teplow, David B; Yamada, Masahito

2010-01-01

265

Interferon in the Cerebrospinal Fluid of Children with Central Nervous System Disorders  

PubMed Central

Interferon was detected in the cerebrospinal fluid (CSF) of 26 of 51 children with aseptic meningitis, two of 44 with bacterial meningitis, and four of 118 with miscellaneous conditions including encephalitis, convulsive disorders and leukemia with neurological involvement. The geometric mean titre of interferon in mumps meningitis was seven to eight times higher than that in enteroviral meningitis; however, levels of interferon were not related to the concentration of leukocytes in CSF from these patients. Interferon titres were relatively greater at the height of the febrile response in children with mumps meningitis or enteroviral meningitis. There was no association between the presence of interferon in the CSF and the isolation of mumps virus or an enterovirus from the same specimen. Patients frequently developed homologous antibody one to three days after signs of aseptic meningitis, obscuring the relationship of interferon production to clinical improvement.

Larke, R. P. Bryce

1967-01-01

266

Technique for repeated collection of cerebrospinal fluid from cisterna magna of anesthetized strain 13 guinea pigs.  

PubMed

To study biochemical changes in cerebrospinal fluid (CSF), we developed a reliable technique for repeated collection of CSF in anesthetized strain 13 guinea pigs. The animal's head was mounted in a stereotaxic instrument with ventral tilt at 30 degrees, and cisternal puncture was made with an L-shaped, 23-gauge needle through the shaved skin. Clear CSF was collected in a 1-ml syringe surrounded by crushed ice. Each collection procedure lasted for 3 min, and three consecutive collections produced about 0.2 ml of CSF. Sampling was repeated at 3-hr intervals. With intravenous saline infusion (10 ml/kg.hr), a total volume of 0.6-1.0 ml of CSF was collected over 6 to 12 hr. Animals maintained a mean blood pressure, heart rate, and minute volume, with few changes during CSF sampling for the entire collection. PMID:1871150

Liu, C T; Guo, Z M

1991-09-01

267

The cerebrospinal fluid provides a proliferative niche for neural progenitor cells  

PubMed Central

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

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

2011-01-01

268

Cerebrospinal Fluid Hypocretin 1 Deficiency, Overweight, and Metabolic Dysregulation in Patients with Narcolepsy  

PubMed Central

Study Objectives: The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls. Patients: 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls. Measurements and Results: Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p < 0.001 and 0.011, respectively). The number of obese patients (BMI > 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups. Conclusions: The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms. Citation: Heier MS; Jansson TS; Gautvik KM. Cerebrospinal fluid hypocretin 1 deficiency, overweight, and metabolic dysregulation in patients with narcolepsy. J Clin Sleep Med 2011;7(6):653-658.

Heier, Mona S.; Jansson, Tine S.; Gautvik, Kaare M.

2011-01-01

269

Prospective Identification of Enteroviruses Involved in Meningitis in 2006 through Direct Genotyping in Cerebrospinal Fluid?  

PubMed Central

Enterovirus infections were investigated with special emphasis on performing rapid molecular identification of enterovirus serotypes responsible for aseptic meningitis directly in cerebrospinal fluid (CSF). Enterovirus genotyping was carried out directly with specimens tested for the diagnostic procedure, using two seminested PCR assays designed to amplify the complete and partial gene sequences encoding the VP1 and VP4/VP2 capsid proteins, respectively. The method was used for identifying the enterovirus serotypes involved in meningitis in 45 patients admitted in 2005. Enterovirus genotyping was achieved in 98% of the patients studied, and we obtained evidence of 10 of the most frequent serotypes identified earlier by genotyping of virus isolates. The method was applied for the prospective investigation of 54 patients with meningitis admitted consecutively in 2006. The enterovirus serotypes involved were identified with the cerebrospinal fluid (CSF) of 52 patients (96%) and comprised 13 serotypes within the human enterovirus B species and 1 within the human enterovirus A species. The three most common serotypes were echovirus 13 (E13; 24%), E6 (23%), and coxsackievirus B5 (11.5%), a pattern different from that observed in 2005. Genotyping of virus isolates was also performed in 35 patients in 2006 (meningitis, n = 31; other diseases, n = 4). By comparison, direct genotyping in CSF yielded a more complete pattern of enterovirus serotypes, thereby allowing the detection of rare serotypes: three less common serotypes (CB2, E21, and E27) were not detected by indirect genotyping alone. The study shows the feasibility of prospective enterovirus genotyping within 1 week in a laboratory setting.

Mirand, Audrey; Henquell, Cecile; Archimbaud, Christine; Chambon, Martine; Charbonne, Francoise; Peigue-Lafeuille, Helene; Bailly, Jean-Luc

2008-01-01

270

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

1984-01-01

271

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

PubMed Central

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

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

1994-01-01

272

Alterations in Protein Regulators of Neurodevelopment in the Cerebrospinal Fluid of Infants with Posthemorrhagic Hydrocephalus of Prematurity*  

PubMed Central

Neurological outcomes of preterm infants with posthemorrhagic hydrocephalus are among the worst in newborn medicine. There remains no consensus regarding the diagnosis or treatment of posthemorrhagic hydrocephalus, and the pathological pathways leading to the adverse neurological sequelae are poorly understood. In the current study, we developed an innovative approach to simultaneously identify potential diagnostic markers of posthemorrhagic hydrocephalus and investigate novel pathways of posthemorrhagic hydrocephalus-related neurological disability. Tandem multi-affinity fractionation for specific removal of plasma proteins from the hemorrhagic cerebrospinal fluid samples was combined with high resolution label-free quantitative proteomics. Analysis of cerebrospinal fluid obtained from infants with posthemorrhagic hydrocephalus demonstrated marked differences in the levels of 438 proteins when compared with cerebrospinal fluid from age-matched control infants. Amyloid precursor protein, neural cell adhesion molecule-L1, neural cell adhesion molecule-1, brevican and other proteins with important roles in neurodevelopment showed profound elevations in posthemorrhagic hydrocephalus cerebrospinal fluid compared with control. Initiation of neurosurgical treatment of posthemorrhagic hydrocephalus resulted in resolution of these elevations. The results from this foundational study demonstrate the significant promise of tandem multi-affinity fractionation-proteomics in the identification and quantitation of protein mediators of neurodevelopment and neurological injury. More specifically, our results suggest that cerebrospinal fluid levels of proteins such as amyloid precursor protein or neural cell adhesion molecule-L1 should be investigated as potential diagnostic markers of posthemorrhagic hydrocephalus. Notably, dysregulation of the levels these and other proteins may directly affect ongoing neurodevelopmental processes in these preterm infants, providing an entirely new hypothesis for the developmental disability associated with posthemorrhagic hydrocephalus.

Morales, Diego M.; Townsend, R. Reid; Malone, James P.; Ewersmann, Carissa A.; Macy, Elizabeth M.; Inder, Terrie E.; Limbrick, David D.

2012-01-01

273

A novel, quantitative assay for homocarnosine in cerebrospinal fluid using stable-isotope dilution liquid chromatography–tandem mass spectrometry  

Microsoft Academic Search

We describe a rapid and sensitive method for the quantification of homocarnosine in physiological fluids, with particular emphasis on cerebrospinal fluid (CSF). Homocarnosine was quantified as the butyl derivative, with 2H2-l-homocarnosine as internal standard. Following deproteinization of CSF samples, supernatants were evaporated to dryness and derivatized with 10% 6M HCl in butanol. Samples were chromatographed on a C18 column and

Erwin E. W. Jansen; K. Michael Gibson; Yosuke Shigematsu; Cornelis Jakobs; Nanda M. Verhoeven

2006-01-01

274

Stasis Theory and Paleontology Discourse  

ERIC Educational Resources Information Center

Stasis theory is a powerful tool for rhetorical analysis, recently under fresh consideration by rhetorical theorists (e.g. Gross) and scholars who identify its utility in the writing classroom (e.g. Carroll). In this study, the author applies stasis theory to a paleontological argument involving a controversial fossil, "Protoavis texensis."…

Northcut, Kathryn M.

2007-01-01

275

Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation.  

PubMed

We have conducted an in vitro coagulation study consisting of two separate groups of 20 subjects using the thrombelastograph. In the first group, haemodilution was performed with a physiological balanced salt solution similar to plasma, with the exception of calcium, and buffered to a normal pH (Plasmalyte B) at 37 degrees C on blood obtained from consenting volunteers. In the second group, a protein-poor body fluid (cerebrospinal fluid (CSF)) obtained from parturient patients undergoing spinal anaesthesia for Caesarean section was used as the diluent. There were statistically significant differences between the warmed Plasmalyte B treated samples and their untreated controls for all variables measured by the thrombelastograph, except for maximum amplitude, and between the CSF treated samples and their untreated controls for all variables. We conclude that electrolyte and acid-base composition of the diluent fluid had no effect on the observation that crystalloid haemodilution produces hypercoagulability. The marked increase in coagulability produced by addition of CSF cannot be explained on a simple haemodilution basis and confirms previous suggestions of the presence of a procoagulant factor in CSF. PMID:10325846

Ruttmann, T G; James, M F; Wells, K F

1999-01-01

276

MicroRNAs in plasma and cerebrospinal fluid as potential markers for Alzheimer's disease.  

PubMed

The development of Alzheimer's disease (AD) biomarkers remains an unmet challenge, and new approaches that can improve current AD biomarker strategies are needed. Recent reports suggested that microRNA (miRNA) profiling of biological fluids has emerged as a diagnostic tool for several pathologic conditions. In this study, we measured six candidate miRNAs (miR-9, miR-29a, miR-29b, miR-34a, miR-125b, and miR-146a) in plasma and cerebrospinal fluid (CSF) of AD and normal subjects by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate their potential usability as AD biomarkers. The qRT-PCR results showed that plasma miR-34a and miR-146a levels, and CSF miR-34a, miR-125b, and miR-146a levels in AD patients were significantly lower than in control subjects. On the other hand, CSF miR-29a and miR-29b levels were significantly higher than in control subjects. Our results provide a possibility that miRNAs detected in plasma and CSF can serve as biomarkers for AD. PMID:24157723

Kiko, Takehiro; Nakagawa, Kiyotaka; Tsuduki, Tsuyoshi; Furukawa, Katsutoshi; Arai, Hiroyuki; Miyazawa, Teruo

2014-01-01

277

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

2012-02-01

278

Production and circulation of cerebrospinal fluid with respect to the subarachnoid space of the optic nerve.  

PubMed

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

2013-01-01

279

Removal of albumin and immunoglobulins from canine cerebrospinal fluid using depletion kits: a feasibility study  

PubMed Central

Background Highly abundant proteins in biological fluids such as serum or cerebrospinal fluid (CSF) can hinder the detection of proteins in lower abundance, e.g., potential biomarkers. Commercial products are available for the depletion of albumin and immunoglobulins (Igs), although most of these kits have not been validated for dog samples. The present study therefore examines the use of different types of depletion kits for dog CSF. Findings Three kits, with different mechanisms for the depletion of albumin and Igs, were tested with dog CSF specimens. One product significantly decreased the amount of albumin; with all kits, IgG was less efficiently removed than albumin. Mass spectrometry of the fractions eluted from the depletion columns revealed considerable co-depletion of other CSF proteins. Conclusions A commercially available depletion kit was identified which depletes albumin and (to a lower extent) immunoglobulins from dog CSF. However, the limited efficacy and the concomitant loss of other proteins from the sample should be taken into account when using this product.

2014-01-01

280

Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.  

PubMed

Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients. PMID:23339019

Yang, Mingchong; Qin, Zhaoyu; Zhu, Yanyan; Li, Yun; Qin, Yanjiang; Jing, Yongsheng; Liu, Shilian

2013-06-01

281

Body Height, Estimated Cerebrospinal Fluid Pressure and Open-Angle Glaucoma. The Beijing Eye Study 2011  

PubMed Central

Purpose To examine potential associations between body height, cerebrospinal fluid pressure (CSFP), trans-lamina cribrosa pressure difference (TLCPD) and prevalence of open-angle glaucoma (OAG) in a population-based setting. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range:50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg]?=?0.44×Body Mass Index[kg/m2]+0.16×Diastolic Blood Pressure[mmHg]-0.18×Age[Years]-1.91 Results Data of IOP and CSFP were available for 3353 (96.7%) subjects. Taller body height was associated with higher CSFP (P<0.001; standardized correlation coefficient beta:0.13; regression coefficient B:0.29; 95% confidence interval (CI):0.25,0.33) after adjusting for male gender, urban region of habitation, higher educational level, and pulse rate. If TLCPD instead of CSFP was added, taller body height was associated with lower TLCPD (P<0.001;beta:?0.10;B:?0.20;95%CI:?0.25,?0.15). Correspondingly, higher CSFP was associated with taller body height (P?=?0.003;beta:0.02;B:0.01;95%CI:0.00,0.02), after adjusting for age, gender, body mass index, pulse, systolic blood pressure, and blood concentration of cholesterol. If IOP was added to the model, higher CSFP was associated with higher IOP (P<0.001;beta:0.02;B:0.02;95%CI:0.01,0.03). TLCPD was associated with lower body height (P?=?0.003;beta:?0.04;B ?0.02,95%CI:?0.04,?0.01) after adjusting for age, body mass index, systolic blood pressure, pulse, blood concentrations of triglycerides, axial length, central corneal thickness, corneal curvature radius, and anterior chamber depth. Adding the prevalence of OAG to the multivariate analysis revealed, that taller body height was associated with a lower OAG prevalence (P?=?0.03;beta:?0.03;B:?1.20;95%CI:?2.28,?0.12) after adjusting for educational level and gender. Conclusions Taller body height was associated with higher CSFP and lower TLCPD (and vice versa), after adjusting for systemic and ocular parameters. Parallel to the associations between a higher prevalence of glaucoma with a lower CSFP or higher TLCPD, taller body height was associated with a lower prevalence of OAG.

Wang, Ya Xing; You, Qi Sheng; Xie, Xiaobin; Yang, Diya; Xu, Liang

2014-01-01

282

Circulating extracellular proteasome in the cerebrospinal fluid: a study on concentration and proteolytic activity.  

PubMed

Alterations of the intracellular ubiquitin-proteasome pathway are found in neurodegenerative and inflammatory disorders of the central nervous system, as well as in its malignancies. Inhibitory substrates of the proteasomes represent promising approaches to control autoimmune inflammations and induction of apoptosis in cancer cells. Extracellular circulating proteasomes are positively correlated to outcome prognosis in hematogenic neoplasias and the outcome in critically ill patients. Previously, we reported raised levels of proteolytic active 20S proteasomes in the extracellular alveolar space in patients with acute respiratory distress syndrome (ARDS). For the cerebrospinal fluid, we assumed that extracellular circulating proteasomes with enzymatic activity can be found, too. Cerebrospinal fluid (CSF) samples of twenty-six patients (14 females, 12 males), who underwent diagnostic spinal myelography, were analyzed for leukocyte cell count, total protein content, lactate and interleukine-6 (Il-6) concentrations. CSF samples were analyzed for concentration and enzymatic activity of extracellular 20S proteasomes (fluorescenic substrate cleavage; femtokatal). Blood samples were analyzed with respect to concentration of extracellular circulating proteasomes. Choroidal plexus was harvested at autopsies and examined with immunoelectron microscopy (EM) for identification of possible transportation mechanisms. Statistical analysis was performed using SPSS (18.0.3). In all patients, extracellular proteasome was found in the CSF. The mean concentration was 24.6 ng/ml. Enzymatic activity of the 20S subunits of proteasomes was positively identified by the fluorescenic subtrate cleavage at a mean of 8.5 fkat/ml. Concentrations of extracellular proteasomes in the CSF, total protein content and Il-6 were uncorrelated. Immunoelectron microscopy revealed merging vesicles of proteasomes with the outer cell membrane suggestive of an exozytic transport mechanism. For the first time, extracellular circulating 20S proteasome in the CSF of healthy individuals is identified and its enzymatic activity detected. A possible exozytic vesicle-bond transportation mechanism is suggested by immunoelectron microscopy. The present study raises more questions on the function of extracellular proteasome in the CSF and encourages further studies on the role of extracellular protesomes in pathological conditions of the central nervous system (tumor lesions and inflammatory processes). PMID:21881828

Mueller, Oliver; Anlasik, Timur; Wiedemann, Jonas; Thomassen, Jan; Wohlschlaeger, Jeremias; Hagel, Vincent; Keyvani, Kathy; Schwieger, Isabel; Dahlmann, Burkhardt; Sure, Ulrich; Sixt, Stephan Urs

2012-03-01

283

Cerebrospinal fluid alkalosis during high-altitude sojourn in unanesthetized ponies.  

PubMed

Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinal fluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinal fluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1-5 days at high altitude (delta PaCO2= - 7.2 mm Hg at 3400 m; - 12.3 mm Hg at 4300 m) and then increased significantly after 6 days of chronic hypoxia (delta PaCO2= + 4.1 mm Hg at 3400 m; + 4.7 mm Hg at 4300 m). Although PaO2 decreased markedly during acute hypoxia, subsequent changes in PaCO2 at high altitude did not alter PaO2 from that observed during acute hypoxia (PaO2=52 mm Hg at 3400 m; 41 mm Hg at 4300 m). The pH of CSF increased during acute hypoxia (delta pH= + 0.013 unit at 3400 m; + 0.033 unit at 4300 m) and became more alkaline after 1-2 days at high altitude (delta pH= + 0.031 unit at 3400 m; + 0.064 unit at 4300 m). At 4300 m, CSF pH remained alkaline to control values throughout sojourn. Under these conditions of chronic hypocapnic hypoxia, CSF pH was imperfectly regulated and regulated in a magnitude equal to (3400 m) or less than (4300 m) arterial blood. Furthermore, the similarity of relative changes in CSF [HCO3-] and arterial [HCO3-] during chronic hypoxia may indicate a passive regulation of CSF [HCO3-] rather than local 'CSF-specific' mechanisms as previously proposed. PMID:241107

Orr, J A; Bisgard, G E; Forster, H V; Buss, D D; Dempsey, J A; Will, J A

1975-10-01

284

Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury.  

PubMed

Danger-associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins that are released from the injured tissues and activate the innate immune system. Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular milieu subsequent to cell death and injury. We hypothesized that cell death within the central nervous system in children with traumatic brain injury (TBI) would lead to the release of mtDNA into the cerebrospinal fluid (CSF) and has the potential to predict the outcome after trauma. Cerebrospinal fluid was collected from children with severe TBI who required intracranial pressure monitoring with Glasgow Coma Scale (GCS) scores of 8 or less via an externalized ventricular drain. Control CSF was obtained in children without TBI or meningoencephalitis who demonstrated no leukocytes in the diagnostic lumbar puncture. The median age for patients with TBI was 6.3 years, and 62% were male. The common mechanisms of injury included motor vehicle collision (35.8%), followed by falls (21.5%) and inflicted TBI (19%); six children (14.2%) died during their intensive care unit course. The mean CSF mtDNA concentration was 1.10E+05 ± 2.07E+05 and 1.63E+03 ± 1.80E+03 copies/?L in the pediatric TBI and control populations, respectively. Furthermore, the mean CSF mtDNA concentration in pediatric patients who later died or had severe disability was significantly higher than that of the survivors (1.63E+05 ± 2.77E+05 vs. 5.05E+04 ± 6.21E+04 copies/?L) (P < 0.0001). We found a significant correlation between CSF mtDNA and high mobility group box 1, another prototypical DAMP, concentrations (? = 0.574, P < 0.05), supporting the notion that both DAMPs are increased in the CSF after TBI. Our data suggest that CSF mtDNA is a novel DAMP in TBI and appears to be a useful biomarker that correlates with neurological outcome after TBI. Further inquiry into the components of mtDNA that modulate the innate immune response will be helpful in understanding the mechanism of local and systemic inflammation after TBI. PMID:24667615

Walko, Thomas D; Bola, R Aaron; Hong, John D; Au, Alicia K; Bell, Michael J; Kochanek, Patrick M; Clark, Robert S B; Aneja, Rajesh K

2014-06-01

285

Changes in cerebrospinal fluid nerve growth factor levels during chick embryonic development.  

PubMed

In the early stages of brain development, cells within the ependymal lining of the neural tube are thought to secrete cerebrospinal fluid (CSF), the so-called neural tube fluid (NTF), whereas before fusion of the neural folds, the neuroepithelium that lines the inside of the neural tube is in contact with amniotic fluid. As the neural tube closes, a membrane formed from these cells invaginates to form the specialized choroid plexus. The choroid plexus is a highly vascularized epithelial cell structure that secretes proteins, including growth factors, into the CSF. Embryonic CSF (e-CSF) contains high concentrations of proteins compared to adult CSF. CSF has been reported to contain nerve growth factor (NGF) and other neurotrophic factors. In this study, total protein concentration and NGF level in e-CSF samples from chick embryos were measured using a dye-based protein assay, enzyme-linked immunosorbent assay (ELISA) and Western blot. The total protein concentration and NGF levels in the CSF decreased from days E10 to E16. There was a rapid increase in total protein content on days E17 and E18, and thereafter the levels decreased from day E19 to day E21. Days E17 and E18 coincide with the onset of neuron migration, proliferation and organization of the cytoarchitecture of the developing cerebral cortex. After that time the total protein concentration and NGF levels decrease until hatching. Since CSF is in contact with the cerebral cortical germinal epithelium, changes in the protein concentration in the CSF could affect neuroepithelial cell proliferation, survival and migration. It is concluded that NGF is not only a constant component of CSF during chick embryogenesis but it might also be involved in cerebral cortical development. PMID:19581095

Mashayekhi, Farhad; Azari, Majid; Moghadam, Lotfali Masomi; Yazdankhah, Meysam; Naji, Mohammad; Salehi, Zivar

2009-10-01

286

Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with high-dosage cefotaxime.  

PubMed Central

We determined cefotaxime and desacetyl-cefotaxime concentrations in children with bacterial meningitis receiving high-dose cefotaxime (300 mg/kg of body weight/day) and concomitant dexamethasone therapy. The median peak cerebrospinal fluid cefotaxime and desacetyl-cefotaxime concentrations were 4.7 and 8.1 microg/ml, respectively. In vitro bactericidal activity (>99.9% killing in 6 h) was found in 17 (94%), 13 (72%), and 8 (44%) of 18 cerebrospinal fluid specimens against cefotaxime-susceptible, -intermediate (MIC, 1 microg/ml), and -resistant (MIC, 4 microg/ml) strains, respectively. High-dose cefotaxime, while safe, is not reliably sufficient therapy for cephalosporin-nonsusceptible pneumococcal meningitis, and combination therapy is recommended.

Friedland, I R; Klugman, K P

1997-01-01

287

A case of anti-GA1 antibody-positive Fisher syndrome with elevated tau protein in cerebrospinal fluid.  

PubMed

We describe a boy with Fisher syndrome. He presented the typical symptoms of Fisher syndrome, including external ophthalmoplegia, abnormality of convergence, and areflexia, after an episode of Campylobacter enterocolitis. Atypically, however, anti-GA1 antibody was detected in his serum, though anti-GQ1b and anti-GT1a antibodies were not. In addition, the tau protein level in his cerebrospinal fluid was elevated. Generally, Fisher syndrome is a self-limiting disease and has a good prognosis. In our patient, however, mild diplopia and areflexia persisted 6 months after their onset. Here, we report on the first Fisher syndrome patient with anti-GA1 antibody in the serum and elevated tau protein in the cerebrospinal fluid. PMID:21742448

Oyazato, Yoshinobu; Shiihara, Takashi; Kusunoki, Susumu; Adachi, Masao; Ohnishi, Noriko; Taniguchi, Hiroaki; Nishiyama, Atsushi; Watanabe, Aika; Kobayashi, Mitsuro; Kamioka, Ichiro

2012-04-01

288

Ventriculocisternal Perfusion Studies in the Monkey. I. Comparison of Radioiodinated (125I) Serum Albumin and Blue Dextran as Indicators to Measure Rate of Formation of Cerebrospinal Fluid.  

National Technical Information Service (NTIS)

The characteristics of two nondiffusible indicators, 125I labeled albumin (RISA-125) and blue dextran, were compared by using them simultaneously to measure rate of formation of cerebrospinal fluid (Vf) in in vitro experiments and in a series of ventricul...

A. N. Martins A. Ramirez A. I. Kobrine T. F. Doyle

1975-01-01

289

Technique for Repeated Collection of Cerebrospinal Fluid from Cisterna Magna of Anesthetized Strain 13 Guinea Pigs. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

To study biochemical changes in cerebrospinal fluid (CSF), we developed a reliable technique for repeated collection of CSF in anesthetized strain 13 guinea pigs. The animal's head was mounted in a stereotaxic instrument with ventral tilt at 30, and ciste...

C. T. Liu Z. M. Guo

1991-01-01

290

Changes in Cerebrospinal Fluid Monoamine Metabolites, Tryptophan, and ?-Aminobutyric Acid during the 1st Year of Life in Normal Infants  

Microsoft Academic Search

Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and ?-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days – preterm days) which reflects the stage of maturity of the central nervous system. These results are

C. Cann-Moisan; E. Girin; J. D. Giroux; P. Le Bras; J. Caroff

1999-01-01

291

[Significance of the determination of lactic acid in the cerebrospinal fluid for the differential diagnosis of meningitis].  

PubMed

Measurement of cerebrospinal fluid lactic acid by an enzymatic test has been evaluated in 164 patients. The upper limit of normal CSF lactate was 300 mg/l. The CSF lactate level is useful for differential diagnosis between partially treated pyogenic meningitis and tuberculous meningitis. The increase of CSF lactate is not specific for meningitis and must be interpreted taking into account the clinical situation. PMID:3892450

el Mdaghri, N; Benbachir, M; Tazi-Lakhsassi, L; Himmich, H

1985-04-01

292

Cerebrospinal fluid and serum concentrations of the N-methyl- d-aspartate (NMDA) receptor antagonist memantine in man  

Microsoft Academic Search

Memantine is a uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist with therapeutic potential in dementia, spasticity and Parkinson's disease. The Ki-value of memantine at the phencyclidine (PCP) binding site of the NMDA receptor is 0.5 ?M in human frontal cortex. We investigated whether concentrations of mementine in cerebrospinal fluid (CSF) and serum samples under therapeutic conditions are in the range of its

J. Kornhuber; G. Quack

1995-01-01

293

Biochemical Characterization of Alzheimer's Soluble Amyloid Beta Protein in Human Cerebrospinal Fluid: Association with High Density Lipoproteins  

Microsoft Academic Search

The soluble form of Alzheimer's amyloid ? protein (sA?) is associated with high density lipoproteins (HDL) in normal human plasma (BBRC,1994,205,1164–1171). Since sA? is also present in cerebrospinal fluid (CSF) and the lipoprotein pattern of CSF is different from that of plasma, it was of interest to ascertain whether the interaction of sA? with HDL also occurs in CSF. Normal

Alexei R. Koudinov; Natalia V. Koudinova; Asok Kumar; Ronald C. Beavis; Jorge Ghiso

1996-01-01

294

Decreased Levels of Soluble Amyloid beta-Protein Precursor in Cerebrospinal Fluid of Live Alzheimer Disease Patients  

Microsoft Academic Search

The amyloid beta-protein is deposited in senile plaques and the cerebrovasculature in Alzheimer disease (AD). Since it is derived from proteolytic processing of its parent protein, the amyloid beta-protein precursor (APP), we investigated whether levels of the secreted forms of APP are altered in cerebrospinal fluid (CSF) of AD patients. Quantitative immunoblotting studies with the anti-APP monoclonal antibody P2-1 revealed

William E. van Nostrand; Steven L. Wagner; W. Rodman Shankle; Jeffrey S. Farrow; Malcolm Dick; Johanna M. Rozemuller; Michael A. Kuiper; Erik C. Wolters; James Zimmerman; Carl W. Cotman; Dennis D. Cunningham

1992-01-01

295

Alterations in Antioxidant Enzyme Activities in Cerebrospinal Fluid Related with Severity of Hypoxic Ischemic Encephalopathy in Newborns  

Microsoft Academic Search

Background: The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free-radical-induced injury. Objective: In this study, we aimed to evaluate the relationship between the activities of antioxidant enzymes [superoxide dismutase (SOD)[, ]glutathione peroxidase (GPX)[, ]and catalase (CAT)] in cerebrospinal fluid (CSF) and severity of hypoxic-ischemic encephalopathy (HIE) in newborns.

Hande Gulcan; I. Cetin Ozturk; Selda Arslan

2005-01-01

296

Effect of ligustrazine on activity changes of angiotensin II in plasma and cerebrospinal fluid in Patients with vascular dementia  

Microsoft Academic Search

Objective: To study the relationship between the activity changes of angiotensin II (Ang II) in plasma, cerebrospinal fluid (CSF) and\\u000a the pathophysiology of vascular dementia (VD) on the one hand and the therapeutic effects of ligustrazine (LIG) on VD and\\u000a its mechanisms on the other hand.Methods: Case grouping: VD group with 50 cases (26 VD patients treated with LIG and

Li Qiang; Wang Jing-zhou; Zhang Li-li; Gao Chang; Zhou Hong-jie; Gao Dong

2003-01-01

297

Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study  

Microsoft Academic Search

In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins ? and ? (sAPP? and sAPP?) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examination?20 in majority of cases)

P Lewczuk; H Kamrowski-Kruck; O Peters; I Heuser; F Jessen; J Popp; K Bürger; H Hampel; L Frölich; S Wolf; B Prinz; H Jahn; Ch Luckhaus; R Perneczky; M Hüll; J Schröder; H Kessler; J Pantel; H-J Gertz; H-W Klafki; H Kölsch; U Reulbach; H Esselmann; J M Maler; M Bibl; J Kornhuber; J Wiltfang

2010-01-01

298

Tau Protein, A?42 and S-100B Protein in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies  

Microsoft Academic Search

The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and ?-amyloid(1–42) (A?42), promising results for the diagnosis of Alzheimer’s disease (AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a

Brit Mollenhauer; Lukas Cepek; Mirko Bibl; Jens Wiltfang; Walter J. Schulz-Schaeffer; Barbara Ciesielczyk; Manuela Neumann; Petra Steinacker; Hans A. Kretzschmar; Sigrid Poser; Claudia Trenkwalder; Markus Otto

2005-01-01

299

Cerebrospinal fluid and serum prealbumin (transthyretin) in patients with multiple sclerosis (MS): Comparison of particular subgroups of MS patients  

Microsoft Academic Search

The levels of prealbumin (PAB, transthyretin) were determined and evaluated in the cerebrospinal fluid (CSF) and serum in\\u000a various subgroups of the multiple sclerosis (MS) patients. In severely disabled patients, serum PAB was elevated more frequently.\\u000a CSF and serum PAB concentrations were higher in treated than in nontreated patients; the values above the upper reference\\u000a limits were also more frequently

M. Hybe?ová; J. Svato?ová; O. Sobek; P. Adam; D. Doležil; D. Adam

2009-01-01

300

Protein concentration of cerebrospinal fluid by precipitation with Pyrogallol Red prior to sodium dodecyl sulphate-polyacrylamide gel electrophoresis  

Microsoft Academic Search

The Pyrogallol Red Molybdate (PRM) and Coomassie Brilliant Blue (CBB) protein dye-binding assays have been applied to samples of cerebrospinal fluid (CSF) to investigate protein concentration by dye precipitation prior to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein concentration values of the CSF samples (N=62) showed good agreement between the PRM and CBB assays as indicated by linear regression

Katherine M Williams; Thomas Marshall

2001-01-01

301

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

2010-01-01

302

Sensitive liquid chromatographic assay for amprenavir, a human immunodeficiency virus protease inhibitor, in human plasma, cerebrospinal fluid and semen  

Microsoft Academic Search

A sensitive bio-analytical assay for amprenavir, a human immunodeficiency virus protease inhibitor, based on reversed-phase liquid chromatography and fluorescence detection, is reported. The analyte is extracted from the matrix, plasma, cerebrospinal fluid (CSF) or semen, with chloroform using propyl-p-hydroxybenzoate as an internal standard. After centrifugation, evaporation of the organic phase and reconstitution in the eluent, the sample is injected into

Rolf W Sparidans; Richard M. W Hoetelmans; Jos H Beijnen

2000-01-01

303

UPLC–MS–MS Analysis of Baicalin in the Cerebrospinal Fluid of Rabbits: Application to a Pharmacokinetic Study  

Microsoft Academic Search

A sensitive and selective ultra-performance liquid chromatographic–tandem mass spectrometric method has been developed for\\u000a analysis of baicalin in the cerebrospinal fluid of rabbits. Samples were separated on a C18 column with a gradient prepared from acetonitrile and 0.3% aqueous formic acid solution as mobile phase. The target compounds\\u000a were quantified by multiple reaction monitoring (MRM) using electrospray ionization (ESI). Intra-and

Shao Liu; Xin-Zhong Li; Li-Min Xu; Peng Lei; Yi-Zeng Liang

2008-01-01

304

Lumbar cerebrospinal fluid pulse wave rising from pulsations of both the spinal cord and the brain in humans  

Microsoft Academic Search

There are two theories regarding the origin of the lumbar cerebrospinal fluid pulse wave (L-CSFPW): that it arises from the arteries supplying the spinal cord, and that it is due to the pulsations of the brain transmitted through the subarachnoid space of the spine.We investigated L-CSFPW of 11 myelopathic patients with a complete (five patients, CB-group) or an incomplete spinal

Kozo Nakamura; Koki Urayama; Yuichi Hoshino

1997-01-01

305

Cerebrospinal Fluid Tau, p-Tau 181 and Amyloid-?38\\/40\\/42 in Frontotemporal Dementias and Primary Progressive Aphasias  

Microsoft Academic Search

Background\\/Aims: We determined cerebrospinal fluid (CSF) concentrations of amyloid-? (A?)1–38, A?1–40, A?1–42, total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer’s dementia (AD, n = 25) and nondemented controls (n = 20). Methods: Commercially available ELISA and electrochemiluminescence

Mirko Bibl; Brit Mollenhauer; Piotr Lewczuk; Hermann Esselmann; Stefanie Wolf; Markus Otto; Johannes Kornhuber; Eckart Rüther; Jens Wiltfang

2011-01-01

306

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

2003-01-01

307

Clinical applications of new cerebrospinal fluid analytic techniques for the diagnosis and treatment of central nervous system infections  

Microsoft Academic Search

Advances in molecular biology and immunology provide new, highly sensitive and specific techniques that can be applied to\\u000a analysis of cerebrospinal fluid to enhance the diagnosis and treatment of central nervous system (CNS) infections. In addition\\u000a to improved accuracy and speed of diagnosis, these modalities may offer improved means of monitoring treatment efficacy, establishing\\u000a prognosis, detecting organism resistance, and tracking

Bruce A. Cohen

2001-01-01

308

A new method for determination of varicella-zoster virus immunoglobulin G avidity in serum and cerebrospinal fluid  

Microsoft Academic Search

BACKGROUND: Avidity determination of antigen-specific immunoglobulin G (IgG) antibodies is an established serological method to differentiate acute from past infections. In order to compare the avidity of varicella-zoster virus (VZV) IgG in pairs of serum and cerebrospinal fluid (CSF) samples, we developed a new technique of avidity testing, the results of which are not influenced by the concentration of specific

Ralf-Herbert Kneitz; Jörg Schubert; Franz Tollmann; Wolfgang Zens; Klaus Hedman; Benedikt Weissbrich

2004-01-01

309

A high-recovery extraction procedure for quantitative analysis of substance P and opioid peptides in human cerebrospinal fluid  

Microsoft Academic Search

This study reports an improved approach for the determination of neuropeptide levels in human cerebrospinal fluid (CSF). The method is based on sample acidification followed by liquid–liquid extraction (LLE) combined with radioimmunoassay. It was applied to study the recovery and level of some opioid peptides (Met-enkephalin-Arg6-Phe7 and Leu-enkephalin-Arg6), substance P and the substance P1–7 fragment, which are all compounds known

Zhurong Liu; Magnus Welin; Björn Bragee; Fred Nyberg

2000-01-01

310

Comparison of Immunosorbent Assays for the Quantification of Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid  

Microsoft Academic Search

Background: The clinical diagnosis of Alzheimer’s disease in early stages may be substantiated by the quantification of the biomarkers Abeta42, Abeta40 and total-Tau (t-Tau) in cerebrospinal fluid (CSF). Different commercially available immunosorbent assays yield reliable results, yet the absolute values obtained may differ in between tests. Methods: We used CSF samples from patients that reported to our memory clinic. Enzyme-linked

C. G. Schipke; S. Prokop; F. L. Heppner; I. Heuser; O. Peters

2011-01-01

311

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

2010-01-01

312

Macrophage inflammatory protein-1? in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases  

Microsoft Academic Search

The level of macrophage inflammatory protein-1? (MIP-1?), a newly discovered cytokine of chemokine family, was determined in cerebrospinal fluid (CSF) from 18 patients with multiple sclerosis (MS) and from control patients with other neurological disorders by an enzyme-linked immunosorbent assay (ELISA). The concentration of MIP-1? in CSF was significantly elevated in MS in relapse (4.4 pg\\/ml) compared with non-inflammatory neurological

Ryuji Miyagishi; Seiji Kikuchi; Toshiyuki Fukazawa; Kunio Tashiro

1995-01-01

313

Cerebrospinal Fluid Penetration and Pharmacokinetics of Vancomycin Administered by Continuous Infusion to Mechanically Ventilated Patients in an Intensive Care Unit  

Microsoft Academic Search

Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after contin- uous infusion (50 to 60 mg\\/kg of body weight\\/day after a loading dose of 15 mg\\/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for a sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic

JACQUES ALBANESE; MARC LEONE; BERNARD BRUGUEROLLE; MARIE-LAURE AYEM; BRUNO LACARELLE; CLAUDE MARTIN

2000-01-01

314

The effect of probenecid on the free and conjugaed 3-methoxy-4-hydroxyphenylglycol (MHPG) in lumbar cerebrospinal fluid.  

PubMed

Free and conjugated lumbar cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured before and after probenecid treatment in 12 schizophrenic patients by a gas liquid chromatography-mass fragmentographic procedure. Neither the free nor conjugated MHPG was appreciably altered by probenecid. Total MHPG was statistically increased by probenecid but not to the point that the probenecid test would be clinically useful for estimating norepinephrine turnover from probenecid-induced changes in MHPG concentrations. PMID:790476

Karoum, F; van Kammen, D P; Bunney, W E; Gillin, J C; Jimerson, D C; Post, R M; Wyatt, R J

1976-01-01

315

Clinical Evaluation of the Gen-Probe Amplified Direct Test for Detection of Mycobacterium tuberculosis Complex Organisms in Cerebrospinal Fluid  

Microsoft Academic Search

Eighty-four cerebrospinal fluid (CSF) samples from different children who presented with signs and symp- toms of meningitis were evaluated for the presence of Mycobacterium tuberculosis complex organisms by the Gen- Probe Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe, San Diego, Calif.). All CSF samples had negative acid-fast smears by the Ziehl-Neelsen staining method. M. tuberculosis was recovered from five samples.

ANNE M. LANG; JESUS FERIS-IGLESIAS; CHABELA PENA; JACQUELINE F. SANCHEZ; LESLIE STOCKMAN; PAUL RYS; GLENN D. ROBERTS; NANCY K. HENRY; DAVID H. PERSING; FRANKLIN R. COCKERILL; Robert Reid

1998-01-01

316

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

317

Vasoactive intestinal peptide-immunoreactive cerebrospinal fluid-contacting neurons in the reptilian lateral septum nucleus accumbens  

Microsoft Academic Search

By means of immunocytochemical demonstration of vasoactive intestinal peptide (VIP) an accumulation of cerebrospinal fluid (CSF)-contacting neurons was found in a circumscribed region of the nucleus accumbens\\/lateral septum of eleven reptilian (chelonian, lacertilian, ophidian, crocodilian) species. Basal processes of these cells contribute to a subependymal plexus whose density displays considerable interspecific variation. VIP-immunoreactive nerve fibers occur also in the lateral

Kanjun Hirunagi; Elke Rommel; Andreas Oksche; Horst-W. Korf

1993-01-01

318

Studies of dementia, depression, electrophysiology and cerebrospinal fluid monoamine metabolites in patients with Parkinson's disease.  

PubMed

Twenty-two patients with Parkinson's disease (PD) were studied by clinical evaluation, assessments of dementia and depression, as well as electrophysiologic examinations for blink reflex (BR), cortical somatosensory evoked potentials (CSEP), brain stem, and long-latency auditory evoked potentials (BAEP, and LAEP), and cerebrospinal fluid (CSF) assays for monoamine metabolites. Results show that PD patients have a significant decrease of Mini-Mental State Examination (MMSE) scores (p < 0.05) and an increase of Hamilton Depression Scale (HDS) scores (p < 0.01), as well as a longer latencies of R2 in BR, N19 and P22 in CSEP, W4 and W5 in BAEP and P300 in LAEP (p < 0.01), and lower CSF levels of HVA and MHPG (p < 0.05). The findings suggest a correlation between dementia/depression and mesocorticolimbic and mesostriatocortic dysfunction with dopaminergic and noradrenergic deficiencies in PD patients. Furthermore, parkinsonian dementia parallels the length of duration of the disease, but not the severity of motor disability. Parkinsonian depression parallels both the length of duration of the disease and the severity of motor disability. PMID:8583235

Chia, L G; Cheng, L J; Chuo, L J; Cheng, F C; Cu, J S

1995-11-01

319

Cerebrospinal fluid-compensated medication reservoir for an implantable infusion device: concept and preliminary evaluation.  

PubMed

Conventional gas-compensated medication reservoirs used for implantable infusion devices require perfect sealing of the gas chamber, because the gases used are generally toxic. In addition, the physical properties of selected gas critically affect the performance of infusion devices and hydraulic performance of the infusion device can be affected by the amount of medication discharged.?In this study, we suggest a new medication reservoir that adopts a cerebrospinal fluid (CSF)-compensating mechanism, such that when a medication is released from the reservoir by a mechanical actuator, native CSF enters into the reservoir to minimize the build-up of pressure drop. We evaluated in vitro performance and conducted in vivo feasibility tests by using an intrathecal infusion device developed at the Korean National Cancer Center. Experimental results showed that the proposed CSF-compensated infusion pump was essentially less affected by ambient temperature or pressure conditions compared to the gas-compensated infusion pump. Moreover, it showed moderate implant feasibility and operating stability during an animal experiment performed for 12 days. We believe that the proposed volume-compensating mechanism could be applied in various medical fields that use implantable devices. PMID:23504815

Nam, Kyoung Won; Choi, Seong Wook; Kim, In Young; Kim, Kwang Gi; Jo, Yung Ho; Kim, Dae Hyun

2013-05-17

320

ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma  

PubMed Central

Background The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. Methods ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. Results Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. Conclusions High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma.

2013-01-01

321

Cerebrospinal fluid nitric oxide metabolites are novel predictors of pain relief in degenerative lumbar diseases.  

PubMed

This study was undertaken to determine whether or not nitric oxide metabolites (NO(2)(-) plus NO(3)(-): NOx levels) in cerebrospinal fluid (CSF) would be predictors of treatment outcome in patients with degenerative lumbar diseases (DLD) including lumbar disc herniation (LDH) and lumbar spinal canal stenosis (LCS). The NOx levels in CSF were measured using an NO analyzer based on the Griess method. Six healthy volunteers and 18 patients with painless diseases were included in the control group. The pre- and postoperative NOx levels in 25 DLD patients, who underwent herniotomy for LDH (17 patients) or selective decompression for LCS (eight patients), were analyzed. The postoperative follow-up periods were approximately 8 months. Nineteen of 25 DLD patients, whose preoperative NOx levels were two standard deviations higher than the mean NOx levels of an age-matched control group, were included in an NO elevated (NOE) group. Among the 25 DLD patients, the preoperative NOx levels in six patients (young LDH group) were within the normal range. The pain-related Japanese Orthopaedic Association score and the Hirabayashi recovery rate were respectively used to evaluate the pain severity and the degree of pain relief. The preoperative and changes of postoperative NOx levels in the NOE group were negatively correlated with the Hirabayashi recovery rate. Normal postoperative NOx levels and excellent pain relief were achieved in young DLD patients. In conclusion, the preoperative and changes in postoperative NOx levels are quantitative predictors of postoperative pain relief in DLD patients. PMID:11376909

Kimura, S; Watanabe, K; Yajiri, Y; Uchiyama, S; Hasegawa, K; Shibuki, K; Endo, N

2001-06-01

322

Chronic lumbar intrathecal catheterization for the collection of cerebrospinal fluid in the canine.  

PubMed

ABSTRACT Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by an excessive production of extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain. Studies have shown that concentrations of tau and amyloid protein (?-amyloid (A?)) are altered in the cerebrospinal fluid (CSF) of patients with AD. In an effort to support the investigation of specialized CSF biomarkers, a reliable and reproducible chronic system was developed to collect lumbar CSF from conscious dogs. Several nonsurgical and surgical procedures have been published for accessing lumbar CSF. We elected to use a lumbar catheter with a vascular access port to collect lumbar CSF. Although the surgical model is not novel, we evaluated various modifications to the procedure and maintenance to increase patency of chronic indwelling lumbar CSF catheters. Different types of catheters were evaluated, and for our purposes a 3.5 Fr open-ended polyurethane catheter was selected. With our final modified surgical procedure and catheter maintenance program, 67% remained patent for longer than 30 days for the first surgery and 86% remained patent for longer than 30 days if a repair or replacement surgery was performed. Based on the results of the proof of concept studies, our model proved to be useful for single and multiple dose pharmacokinetic studies in a search for effective Alzheimer's disease treatment. PMID:24694254

West, Wanda; Ehrmann, Jon; Johnson, Wendy

2014-08-01

323

Segmentation of brain parenchyma and cerebrospinal fluid in multispectral magnetic resonance images.  

PubMed

Presents a new method to segment brain parenchyma and cerebrospinal fluid spaces automatically in routine axial spin echo multispectral MR images. The algorithm simultaneously incorporates information about anatomical boundaries (shape) and tissue signature (grey scale) using a priori knowledge. The head and brain are divided into four regions and seven different tissue types. Each tissue type c is modeled by a multivariate Gaussian distribution N(mu(c),Sigma(c)). Each region is associated with a finite mixture density corresponding to its constituent tissue types. Initial estimates of tissue parameters {mu(c),Sigma(c )}(c=1,...,7) are obtained from k-means clustering of a single slice used for training. The first algorithmic step uses the EM-algorithm for adjusting the initial tissue parameter estimates to the MR data of new patients. The second step uses a recently developed model of dynamic contours to detect three simply closed nonintersecting curves in the plane, constituting the arachnoid/dura mater boundary of the brain, the border between the subarachnoid space and brain parenchyma, and the inner border of the parenchyma toward the lateral ventricles. The model, which is formulated by energy functions in a Bayesian framework, incorporates a priori knowledge, smoothness constraints, and updated tissue type parameters. Satisfactory maximum a posteriori probability estimates of the closed contour curves defined by the model were found using simulated annealing. PMID:18215837

Lundervold, A; Storvik, G

1995-01-01

324

Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections.  

PubMed

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. PMID:23781068

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

2013-01-01

325

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis.  

PubMed Central

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of < 1, 1 to 2, and > 2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is < 1 mmol/liter on admission.

Gaillard, J L; Silly, C; Le Masne, A; Mahut, B; Lacaille, F; Cheron, G; Abadie, V; Hubert, P; Matha, V; Coustere, C

1995-01-01

326

Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy.  

PubMed

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone. PMID:8067769

Gaillard, J L; Abadie, V; Cheron, G; Lacaille, F; Mahut, B; Silly, C; Matha, V; Coustere, C; Lokiec, F

1994-05-01

327

Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy.  

PubMed Central

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone.

Gaillard, J L; Abadie, V; Cheron, G; Lacaille, F; Mahut, B; Silly, C; Matha, V; Coustere, C; Lokiec, F

1994-01-01

328

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

PubMed Central

Background and Purpose Multifocal seeding of the leptomeninges by malignant cells, which is usually referred to as leptomeningeal carcinomatous metastasis, produces substantial morbidity and mortality. The diagnosis of leptomeningeal metastasis is usually established by cerebrospinal fluid (CSF) investigation, including cytology, cell counts, protein, glucose, and a tumor marker such as carcinoembryonic antigen (CEA). This study examined the diagnostic value of CEA in the CSF. Methods We measured the CSF CEA level in 32 patients with leptomeningeal metastasis. The control group consisted of 19 cancer patients without leptomeningeal metastasis. CEA was measured by the chemiluminescent emission method. Results The CEA level was significantly higher in patients with leptomeningeal metastasis than in the control group (p<0.005). The level of CSF protein was higher and that of CSF glucose was lower in patients with leptomeningeal metastasis than in the control group (p<0.005). Conclusions The CSF CEA level is useful for diagnosing leptomeningeal carcinomatous metastasis. The CSF levels of protein and glucose are also useful in the diagnosis.

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

2010-01-01

329

Cerebrospinal fluid amino compounds in Parkinson's disease. Alterations due to carbidopa/levodopa.  

PubMed

Employing a triple-column ion-exchange/fluorometric procedure, 29 amino compounds, including amino acid neurotransmitters, were measured in lumbar cerebrospinal fluid (CSF) from two groups of patients with idiopathic Parkinson's disease de novo (n = 6) and those who were treated with carbidopa/levodopa (n = 6), and from neurologically normal controls (n = 10). Consideration was given to in vivo and in vitro factors known to influence levels of various CSF constituents. Results showed statistically significant decreases in the levels of gamma-aminobutyric acid, homocarnosine, phosphoethanolamine, and threonine, and elevation of ornithine levels, in the CSF of de novo patients with Parkinson's disease compared with controls. These changes "normalized" following treatment with carbidopa/levodopa. This study suggests that Parkinson's disease may be characterized by defects in specific amino compound metabolic pathways, resulting in central nervous system amino compound imbalances that may contribute to the pathophysiology of this disorder. Carbidopa/levodopa therapy tends to "normalize" these amino compound imbalances. PMID:3337677

Manyam, B V; Ferraro, T N; Hare, T A

1988-01-01

330

Diagnostic Accuracy of Cerebrospinal Fluid (CSF) Cytology in Metastatic Tumors: An Analysis of Consecutive CSF Samples  

PubMed Central

Background Cerebrospinal fluid (CSF) examination can be used to verify the presence of primary malignancies as well as cases of central nervous system (CNS) metastasis. Because of its importance, there have been several studies concerning the sensitivity of CSF cytology. To determine the practical use and reproducibility of diagnoses based on CSF cytology, we evaluated this test by analyzing cytology results from consecutive CSF samples. Methods Between July 2010 and June 2013, 385 CSF cytology samples from 42 patients were collected. The samples were gathered using a ventricular catheter and reservoir. CSF cytology of all patients was examined more than two times with immunocytochemistry for cytokeratin. Results Primary neoplastic sites and histologic types of patients' metastatic cancer were diverse. The overall sensitivity for detecting malignancy was 41.3%. Even within short-term intervals, diagnoses frequently changed. Conclusions Our results were inconsistent, with low sensitivity, when compared to the results of previous studies. However, CSF evaluation can still provide valuable diagnostic and prognostic information because adjuvant treatments are now routinely performed in patients with CNS metastasis. Negative CSF cytology results should not be ignored, and continuous CSF follow-up is essential for following the clinical course of patients with metastatic cancer involving the CNS.

Bae, Yoon Sung; Cheong, June-Won; Chang, Won Seok; Kim, Sewha; Oh, Eun Ji

2013-01-01

331

Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse  

PubMed Central

The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process.

2011-01-01

332

Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis  

PubMed Central

Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.

Fuvesi, Judit; Hanrieder, Jorg; Bencsik, Krisztina; Rajda, Cecilia; Kovacs, S. Krisztian; Kaizer, Laszlo; Beniczky, Sandor; Vecsei, Laszlo; Bergquist, Jonas

2012-01-01

333

Proteomic analysis of the cerebrospinal fluid of patients with lumbar disk herniation.  

PubMed

To better understand the pathophysiologic mechanisms underlying spinal nerve root injury induced by lumbar disk herniation (LDH), comparative proteomic analysis of cerebrospinal fluid (CSF) between patients with LDH (the experiment group) and the otherwise healthy patients who had had implants removed from healed fractures in the lower limbs (the control group) was carried out using 2-DE followed by LC-IT-MS and database searching. Image analysis of silver-stained 2-DE gels revealed that 15 protein spots showed significant differential expression between the two groups of CSF samples (p < 0.05). After searching the database we found that in CSF of LDH patients, the expression of cystatin C, apolipoprotein A-IV, vitamin D-binding protein, neurofilament triplet L protein, IgG, tetranectin, and hemoglobin were elevated. However, ProSAAS, prostagladin D2 synthase, creatine kinase B, superoxide dismutase 1 and peroxiredoxin 2 were decreased. The subsequent ELISA measured the concentration of tetranectin, vitamin D-binding protein and cystatin C and confirmed the results of proteomic analysis. These identified proteins are involved in the pathophysiological process of spinal nerve root injury caused by herniated lumbar disk. The functional implications of the alterations in the levels of these proteins are discussed in this paper. PMID:16372267

Liu, Xu-Dong; Zeng, Bing-Fang; Xu, Jian-Guang; Zhu, Hai-Bo; Xia, Qi-Chang

2006-02-01

334

Determination of metabolic organic acids in cerebrospinal fluid by microchip electrophoresis.  

PubMed

A new MCE method for the determination of oxalic, citric, glycolic, lactic, and 2- and 3-hydroxybutyric acids, indicators of some metabolic and neurological diseases, in cerebrospinal fluid (CSF) was developed. MCE separations were performed on a PMMA microchip with coupled channels at lower pH (5.5) to prevent proteins interference. A double charged counter-ion, BIS-TRIS propane, was very effective in resolving the studied organic acids. The limits of detection (S/N = 3) ranging from 0.1 to 1.6 ?M were obtained with the aid of contact conductivity detector implemented directly on the microchip. RSDs for migration time and peak area of organic acids in artificial and CSF samples were <0.8 and <9.7%, respectively. Recoveries of organic acids in untreated CSF samples on the microchip varied from 91 to 104%. Elimination of chloride interference, a major anionic constituent of CSF, has been reached by two approaches: (i) the use of coupled channels microchip in a column switching mode when approximately 97-99% of chloride was removed electrophoretically in the first separation channel and (ii) the implementation of micro-SPE with silver-form resin prior to the MCE analysis, which selectively removed chloride from undeproteinized CSF samples. PMID:24431209

Dan?, Ladislav; Bodor, Róbert; Troška, Peter; Hor?i?iak, Michal; Masár, Marián

2014-08-01

335

Neuronal and Glia-Related Biomarkers in Cerebrospinal Fluid of Patients with Acute Ischemic Stroke  

PubMed Central

BACKGROUND Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). METHODS A total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. RESULTS Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test). CONCLUSIONS Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

Hjalmarsson, Clara; Bjerke, Maria; Andersson, Bjorn; Blennow, Kaj; Zetterberg, Henrik; Aberg, N David; Olsson, Bob; Eckerstrom, Carl; Bokemark, Lena; Wallin, Anders

2014-01-01

336

Analysis of cerebrospinal fluid ?-aminobutyric acid by capillary electrophoresis with laser-induced fluorescence detection.  

PubMed

The measurement of ?-aminobutyric acid (GABA) is suitable for investigating various neurological disorders. In this study, a sensitive and selective method for free GABA quantification in cerebrospinal fluid (CSF) has been standardised. This method is based on CE with LIF detection using 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-F) as a derivatisating agent. The reaction conditions (NBD-F concentration, pH, temperature and reaction time) and the electrophoretic parameters (run buffer composition and pH and separation voltage) were optimised to obtain the maximum derivatisation efficiency and electrophoretic resolution. The best resolution was obtained using 200 mM sodium borate, 10 mM SDS, 8.5 mM ?-CD, pH 10 and 20 kV voltage. The method was linear in the concentration range of 2.5-1000 nM with good inter- and intra-assay precision values. The effects of CSF handling on free GABA concentrations were also evaluated. Our results show that the time delay between CSF collection and freezing strongly increases the CSF GABA values. Age-related reference values were established in 55 paediatric controls. The influence of antiepileptic therapy on free CSF GABA was studied in 38 neuropaediatric patients. Significantly, higher GABA values were obtained in patients taking valproic acid or vigabatrin therapy, which are antiepileptic drugs that modulate GABA metabolism. PMID:24338894

Casado, Mercedes; Molero, Marta; Sierra, Cristina; García-Cazorla, Angels; Ormazabal, Aida; Artuch, Rafael

2014-04-01

337

Coefficient of energy balance, a new parameter for basic investigation of the cerebrospinal fluid.  

PubMed

Abstract Background: The concentrations of glucose and lactate in cerebrospinal fluid (CSF) provide important information about energy metabolism in the CSF compartment. To improve our understanding of this information we introduced a new parameter resulting from a formula for calculating the fictitious production of adenosine triphosphate, i.e., the coefficient of energy balance (KEB). Methods: We evaluated cytology, the concentrations of glucose and lactate and the KEB in the CSF of 948 patients, who were divided into five groups. For statistical analysis we used the Kruskal-Wallis test with post-hoc analysis using the Dunn method and multinomial regression analysis. We determined the specificities and sensitivities of the cytological pictures and the KEB. Results: A KEB>28.0 corresponded to normal energy metabolism in the CSF. A KEB<28.0 corresponded to an increased level of anaerobic metabolism in the CSF during inflammation in the CNS. A KEB<10.0 corresponded to a high level of anaerobic metabolism in the CSF during severe inflammation with an oxidative burst of professional phagocytes in the CNS. The KEB parameter increased the specificities of cytological examinations of the CSF in all cases. Conclusions: The KEB represents an equation for calculating the fictitious average number of ATP molecules produced in the CSF compartment from one molecule of glucose, and we used it successfully as a new parameter for evaluating energy metabolism status in the CSF. PMID:24622789

Kelbich, Petr; Hej?l, Aleš; Krulichová, Iva Selke; Procházka, Jan; Hanuljaková, Eva; Peruthová, Jitka; Koudelková, Martina; Sameš, Martin; Krejsek, Jan

2014-07-01

338

Identification of peptides specific for cerebrospinal fluid antibodies in multiple sclerosis by using phage libraries.  

PubMed Central

The study of the origin and pathogenetic relevance of the oligoclonal antibodies present in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients has been hampered by a lack of specific ligands. We recently reported a general strategy, based on phage-displayed random peptide libraries, to identify ligands for disease-specific antibodies even in the absence of any information on the nature of the pathologic antigen. With this procedure, we identified several peptides specifically recognized by antibodies present in the CSF of MS patients. Using these peptides as reagents, we demonstrated that they mimic different natural epitopes and react with antibodies enriched in the CSF of MS patients. Antibodies recognizing the selected peptides are commonly found with equal frequency in the sera of MS patients and of normal individuals. In contrast, the repertoire of CSF antibodies appears to be individual-specific and is probably the result of a nonspecific immunodysregulation rather than a stereotyped response to a single antigen/agent. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5

Cortese, I; Tafi, R; Grimaldi, L M; Martino, G; Nicosia, A; Cortese, R

1996-01-01

339

Conformation-Dependent Oligomers in Cerebrospinal Fluid of Presymptomatic Familial Alzheimer's Disease Mutation Carriers  

PubMed Central

Background/Aims Oligomerization of amyloid beta (A?) is a hypothesized step in the formation of plaques in Alzheimer's disease (AD) but has been difficult to demonstrate in vivo in humans. As persons destined to develop familial AD (FAD) due to fully penetrant autosomal dominant mutations are essentially certain to develop the disease, they provide the opportunity to identify oligomers during the presymptomatic stage of the disease. Methods We measured levels of A?42 using a conventional immunoassay and prefibrillar, fibrillar, and annular protofibrillar oligomers using polyclonal conformation-dependent antibodies in the cerebrospinal fluid (CSF) of 7 persons at risk for inheriting FAD mutations. Levels of oligomers were compared between FAD mutation carriers and noncarriers. Results Compared to 2 noncarriers, annular protofibrillar oligomers were elevated, prefibrillar and fibrillar oligomers trended towards elevation and A?42 monomer trended towards being decreased in 5 FAD mutation carriers. Conclusion Our data provide evidence for an identifiable elevation of CSF oligomers during the presymptomatic phase of FAD.

Ringman, John M.; Tomic, Jennifer L.; Coppola, Giovanni; Elashoff, David; Gylys, Karen H.; Glabe, Charles G.

2012-01-01

340

[Neuropathic pain enhances expression of HCN2 channel in rat cerebrospinal fluid-contacting nucleus].  

PubMed

The purpose of this research is to explore the distribution and expression of hyperpolarization-activated cyclic nucleotide-gated channels subtype 2 (HCN2) in cerebrospinal fluid (CSF)-contacting nucleus in neuropathic pain, and provide experimental evidence to reveal the biological function and regulation mechanisms of CSF-contacting nucleus in neuropathic pain. Neuropathic pain model was produced by chronic constriction injury (CCI) in Sprague-Dawley (SD) rats. Intracerebroventricular injection of cholera toxin subunit B (CTb) labeled with horseradish peroxidase (CB-HRP) was used to specifically mark distal CSF-contacting nucleus. The thermal withdrawal latency and mechanical withdrawal threshold of rats were recorded to detect the change of pain threshold. The expressions HCN2 channel and c-Fos proteins in CSF-contacting nucleus were detected by immunofluorescence and Western blot. The results showed that, compared with the control group, CTb-treated rats did not show any differences in the expressions of HCN2 channel and c-Fos proteins in CSF-contacting nucleus, as well as pain threshold. At 7, 14 d after CCI operation, the model rats showed not only significantly increased expressions of HCN2 channel and c-Fos in CSF-contacting nucleus, but also decreased pain threshold. ZD7288, a HCN2 channel blocker, could reverse the above changes in neuropathic pain model rats. These results suggest that the CSF-contacting nucleus may be involved in the process of neuropathic pain via the HCN2 channel. PMID:24964850

Wu, Tong; Cao, Jing; Zhang, Li-Cai

2014-06-25

341

Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS.

Ranganathan, Srikanth; Williams, Eric; Ganchev, Philip; Gopalakrishnan, Vanathi; Lacomis, David; Urbinelli, Leo; Newhall, Kristyn; Cudkowicz, Merit E.; Brown, Robert H.; Bowser, Robert

2006-01-01

342

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

PubMed

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

2013-01-01

343

Sandwich grafting technique for endoscopic endonasal repair of cerebrospinal fluid rhinorrhoea.  

PubMed

The surgical management of cerebrospinal fluid (CSF) rhinorrhoea has changed significantly after the introduction of functional endoscopic sinus surgery. The clear anatomical exposure of the roof of the nasal and paranasal sinus cavities by the endoscope offers the surgeon a golden chance to identify the area of CSF leak, and thus enables one to adequately plan the management. The aim of this work is to evaluate the use of facia lata sandwich graft technique for endoscopic endonasal repair of CSF rhinorrhoea. Forty patients with CSF rhinorrhoea were treated endoscopically using 2 layers of facia lata (underlay and onlay) interposed with a layer of septal cartilage or conchal bone in-between (sandwich technique) for repair. Fifty-five percent of cases were regarded as spontaneous CSF leaks with no obvious cause, 30% following head injury and 15% were iatrogenic. The ethmoidal roof was the commonest location of CSF leak (60%) followed in frequency by the cribriform plate and the sphenoid sinus (20% each). Follow-up period was 12-24 months. We have achieved a 95% success rate in managing CSF leaks in our 40 patients in the first attempt repair and 100% success rate after second attempt repair. Endoscopic endonasal repair of CSF leaks is quite safe and effective procedure with high success rate and avoid the morbidity associated with craniotomy. Using the three-layer, sandwich-grafting technique of facia lata further adds more security to the sealing of CSF and augments the results of repair. PMID:23982671

Saafan, Magdy Eisa; Albirmawy, Osama A; Tomoum, Mohamed Osama

2014-05-01

344

Endoscopic Contralateral Superiorly Based Mucoperiosteal Nasal Septal Flap for Closure of Cerebrospinal Fluid Leak  

PubMed Central

Objective A novel local contralateral superiorly based mucoperiosteal nasal septal flap (CSBMNSF) for closure of a cerebrospinal fluid (CSF) leak from the middle anterior base of the skull is described. Materials and Methods A retrospective review of patients having endoscopic sinus surgery (ESS) with a CSF leak between 2000 and 2009 was performed. The surgical technique is described. Two vertical parallel incisions are performed anteriorly and posteriorly in the contralateral septal mucosa, joined inferiorly by a horizontal incision. Elevation of the flap is completed, leaving it pedicled superiorly. A window is created at the highest aspect of the nasal septum to allow transfer of the flap to the affected side. Results Four patients with a CSF leak post-ESS for excision of a congenital meningocele, tumor removal, and chronic sinusitis are described. All were treated successfully using a CSBMNSF. Conclusion A novel, easy-to-handle local flap for closure of defects in the anterior middle skull base is described. The use of this flap offers less morbidity and less bulkiness compared with other local or regional flaps.

Eviatar, Ephraim; Gavriel, Haim

2013-01-01

345

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

NASA Astrophysics Data System (ADS)

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

Harbater, Osnat; Gannot, Israel

2014-03-01

346

Increased intrathecal nitric oxide formation in multiple sclerosis; cerebrospinal fluid nitrite as activity marker.  

PubMed

Nitric oxide is formed from L-arginine by a family of enzymes: nitric oxide synthase (NOS). The inducible nitric oxide synthase is activated by cytokines and it has been suggested that activation of the enzyme gives rise to neurotoxic levels of reactive nitrogen oxides. This enzyme has been shown to be localized in multiple sclerosis (MS) lesions but the role of nitric oxide formation in the pathogenesis of MS is still unclear. Using capillary electrophoresis, we have analysed nitrite and nitrate in cerebrospinal fluid (CSF) and demonstrate increased levels of reactive nitrogen products in 17 patients with MS. The total levels of oxidized nitrogen products were significantly elevated in MS patients when compared with controls. In patients with active MS, nitrite levels were significantly increased when compared with controls and patients in remission. This is supportive of NOS induction in MS. We suggest that capillary electrophoresis analysis of nitrite and nitrate in CSF could provide a clinically useful way to determine disease activity in MS. PMID:10457392

Brundin, L; Morcos, E; Olsson, T; Wiklund, N P; Andersson, M

1999-09-01

347

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

2012-01-01

348

Detection of enterovirus RNA in cerebrospinal fluid: comparison of two molecular assays.  

PubMed

Enterovirus (EV) and human parechovirus (HPeV) are a major cause of infection in childhood. A rapid diagnostic test may improve the management of patients with EV and HPeV infection. The aim of this study is to evaluate the performance of the GeneXpert enterovirus assay (GXEA) for detection of EV RNA compared to a user-developed reverse-transcriptase (RT) quantitative real-time PCR (qPCR) in routine clinical practice. Also a RT-qPCR assay for detection of HPeV RNA in different clinical samples was developed and evaluated. Cerebrospinal fluid (CSF) from 232 patients suspected for meningitis was collected and tested for EV and HPeV using RT-qPCR assays. In parallel an aliquot of the samples was tested using the GXEA and viral culture. EV RNA was detected in 22 (19.0%) and 28 (24.1%) of 116 samples using the GXEA and RT-qPCR assay, respectively. EV was isolated from 10 of 116 (8.6%) samples by viral culture. GXEA had a sensitivity, specificity, positive predictive value and negative predictive value of 82.1%, 100%, 100% and 96.2%, respectively. In this study, molecular assays were superior to viral culture for detecting EV RNA in CSF. GXEA showed a high specificity but a lower sensitivity for the detection of EV RNA compared to the RT-qPCR assay. PMID:22024398

de Crom, S C M; Obihara, C C; van Loon, A M; Argilagos-Alvarez, A A; Peeters, M F; van Furth, A M; Rossen, J W A

2012-01-01

349

Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.  

PubMed

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities. PMID:22929030

Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

2013-04-01

350

Cerebrospinal fluid-iophendylate contrast on gradient-echo MR images.  

PubMed

The effect on the signal intensities of cerebrospinal fluid (CSF) and iophendylate (Pantopaque) and on CSF-iophendylate contrast was studied in vitro with a small-nutation-angle (alpha) gradient refocused magnetic resonance (MR) imaging technique (GRASS) as alpha, repetition time (TR), and echo time (TE) were varied. CSF signal intensity was consistently greater than that of iophendylate. Therefore, retained intraspinal iophendylate may be considered in the differential diagnosis of focal areas of low signal intensity at the periphery of the spinal canal on GRASS images. At constant TE and TR, an increase in alpha from 6 degrees to 45 degrees increased the signal intensities of CSF and iophendylate but decreased CSF-iophendylate contrast. At constant alpha and TR, an increase in TE from 13 to 28 msec decreased the signal intensities of CSF and iophendylate but increased contrast. At constant alpha and TE, an increase in TR from 50 to 400 msec increased the signal intensities of CSF and iophendylate, as well as contrast. Clinical examples of the contrast behavior of retained intraspinal iophendylate on both spin-echo and GRASS images corroborate the experimental findings. Retained intraspinal iophendylate may mimic the appearance of intra-or extra-dural lesions, magnetic susceptibility artifact, and flow on gradient-echo MR images of the spine. PMID:3175007

Jack, C R; Gehring, D G; Ehman, R L; Felmlee, J P

1988-11-01

351

Cerebrospinal fluid drainage and cranial decompression prolong survival in rats with fulminant hepatic failure  

PubMed Central

Summary Fulminant hepatic failure (FHF) is a devastating disease. Liver transplantation is the definitive treatment. However, a third of these patients die due to brain edema before a donor becomes available. Cerebrospinal fluid (CSF) drainage and decompressive craniectomy have been used to treat brain edema in brain trauma and hemispheric stroke. However, their role in brain edema associated with FHF has not been examined. In this study we evaluated the potential effects of CSF drainage and decompressive craniectomy on survival in FHF using an experimental model in rats. In CSF drainage experiments all animals had ventriculostomy placed. Five days later FHF was induced with d-galactosamine. Those FHF rats that progressed into comatose stages either received CSF aspiration or did not. In separate experiments the study rats had either a decompressive craniectomy or a sham procedure. FHF was induced 5 days later. We found that both CSF drainage and decompressive craniectomy significantly increased survival of FHF rats compared with the controls: 53.2 ± 1.1 vs. 48.7 ± 1.5 h (P = 0.031), and 69.4 ± 3.9 vs. 53.7 ± 3.2 h (P = 0.009), respectively. In conclusion, these findings suggest that CSF drainage and decompressive craniectomy may increase the window of opportunity for liver transplantation.

Yamamoto, Satoshi; Steers, Jeffery L.; Wharen, Robert E.; Eckman, Christopher B.; Nguyen, Justin H.

2009-01-01

352

Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span.  

PubMed

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

2013-10-01

353

Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections.  

PubMed

Varicella-zoster virus (VZV) is one of our most common viruses causing central nervous system (CNS) infection with sometimes severe neurological complications. Glial fibrillary acidic protein (GFAp), light subunit of neurofilament protein (NFL) and S-100? protein are cerebrospinal fluid (CSF) biomarkers that have been used to estimate the severity of brain damage and outcome in various CNS diseases. So far, these biomarkers have not been utilised to investigate glial pathology and neuronal damage in patients with VZV CNS infections. In this prospective study, we measured CSF GFAp, NFL and S-100? as markers of brain damage in 24 patients with acute neurological manifestations and VZV DNA detected in CSF by PCR and compared with a control group (n = 14). Concentrations of CSF NFL and GFAp were increased in patients with VZV CNS infection compared with controls (p = 0.002 and p = 0.03) while levels of S-100? were reduced. In patients with VZV encephalitis the elevations of CSF NFL and GFAp were more pronounced compared with patients with other VZV CNS syndromes. No correlations between the levels of biomarkers and viral load, neurological sequels or clinical outcome were found in this limited number of patients. These results indicate that VZV induces neuronal damage and astrogliosis with more severe brain damage in patients with VZV encephalitis than in patients with other neurological complications caused by this virus. PMID:23471614

Grahn, Anna; Hagberg, Lars; Nilsson, Staffan; Blennow, Kaj; Zetterberg, Henrik; Studahl, Marie

2013-07-01

354

Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis  

PubMed Central

Background: Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. Methods: The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. Results: The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. Conclusions: The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics.

Rossitti, Sandro

2013-01-01

355

White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults.  

PubMed

We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (A?42 and A?42/p-Tau181) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF A?42/p-Tau181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures. PMID:24866404

Gold, Brian T; Zhu, Zude; Brown, Christopher A; Andersen, Anders H; LaDu, Mary Jo; Tai, Leon; Jicha, Greg A; Kryscio, Richard J; Estus, Steven; Nelson, Peter T; Scheff, Steve W; Abner, Erin; Schmitt, Frederick A; Van Eldik, Linda J; Smith, Charles D

2014-10-01

356

Increase in cerebrospinal fluid F2-isoprostanes is related to cognitive decline in APOE ?4 carriers.  

PubMed

In this longitudinal study we investigated the effect of apolipoprotein E (APOE) genotype on the relation between cognitive decline and cerebrospinal fluid (CSF) F2-isoprostanes, the reference marker for oxidative stress. Twenty non-demented subjects, 58 mild cognitive impairment (MCI) patients, and 63 Alzheimer's disease (AD) patients with measurements of CSF F2-isoprostanes at two time points (with a mean interval of 2.0 ± 1.1 years) and known APOE genotype were included. Mean clinical follow-up time was 3.9 ± 2.4 years. For change in F2-isoprostanes over time and associations with Mini-Mental State Examination scores, age- and gender-adjusted linear mixed models were used. Analyses were done for APOE ?4 carriers and non-carriers separately. In APOE ?4 carriers, annual change in F2-isoprostane levels appeared larger than in APOE ?4 non-carriers (?[SE] 2.5[0.5], p < 0.001 versus 1.8[0.5], p < 0.01). In addition, increase in F2-isoprostanes was associated with further cognitive decline in APOE ?4 carriers (p < 0.05), but not in non-carriers (p = 0.28). Our results reiterate the importance of oxidative stress in neurodegeneration, especially in APOE ?4 carrying patients. Future studies should focus on the possibility of increased vulnerability to oxidative damage in APOE ?4 carriers. PMID:23629585

Duits, Flora H; Kester, Maartje I; Scheffer, Peter G; Blankenstein, Marinus A; Scheltens, Philip; Teunissen, Charlotte E; van der Flier, Wiesje M

2013-01-01

357

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.

2003-11-01

358

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.

1981-09-01

359

Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain.  

PubMed

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of VEGF during bacterial meningitis, VEGF was measured in cerebrospinal fluid (CSF) and blood of 37 patients with bacterial meningitis and 51 control patients, including 16 patients with viral meningitis. Circulating VEGF levels were similar in bacterial meningitis patients and control patients. VEGF(CSF) was detected in 11 (30%) of 37 of bacterial meningitis patients (range, <25-633 pg/mL) but in none of the control patients. The median VEGF index was 6.2 (range, 0.6-42), indicating intrathecal production. Median CSF cell counts, protein levels, and CSF: serum albumin ratios were higher for patients with detectable VEGF(CSF), although the difference was not statistically significant. VEGF immunoreactivity in autopsy brain specimens was found in the inflammatory infiltrate of patients with bacterial meningitis. These results indicate that inflammatory cells secrete VEGF during bacterial meningitis and that VEGF may contribute to blood-brain barrier disruption. PMID:11106541

van der Flier, M; Stockhammer, G; Vonk, G J; Nikkels, P G; van Diemen-Steenvoorde, R A; van der Vlist, G J; Rupert, S W; Schmutzhard, E; Gunsilius, E; Gastl, G; Hoepelman, A I; Kimpen, J L; Geelen, S P

2001-01-01

360

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

PubMed Central

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.

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

2013-01-01

361

Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta  

PubMed Central

The use of quantitative endophenotypes in genetic studies may provide greater power, allowing for the use of powerful statistical methods and a biological model for the effects of the disease-associated genetic variation. Cerebrospinal fluid (CSF) amyloid beta (A?) levels are promising endophenotypes for late-onset Alzheimer’s disease (LOAD) and show correlation with LOAD status and A? deposition. In this study, we investigated 29 single nucleotide polymorphisms (SNPs) positive in AlzGene (http://www.alzgene.org) meta-analyses, for association with CSF A? levels in 313 individuals. This study design makes it possible to replicate reported LOAD risk alleles while contributing novel information about the mechanism by which they might affect that risk. Alleles in ACE, APOE, BDNF, DAPK1, and TF are significantly associated with CSF A? levels. In vitro analysis of the TF SNP showed a change in secreted A? consistent with the CSF phenotype and known Alzheimer’s disease variants, demonstrating the utility of this approach in identifying SNPs that influence risk for disease via an A?-related mechanism.

Kauwe, John S. K.; Wang, Jun; Mayo, Kevin; Morris, John C.; Fagan, Anne M.; Holtzman, David M.; Goate, Alison M.

2009-01-01

362

Characterization of the human cerebrospinal fluid phosphoproteome by titanium dioxide affinity chromatography and mass spectrometry.  

PubMed

Biomarkers in the cerebrospinal fluid (CSF) may be important for the diagnosis of chronic degenerative disorders in the central nervous system including dementia. Existing CSF biomarkers for dementia, however, are relatively nonspecific. More specific markers may be found by targeting investigations based on knowledge of the molecular pathology of the disease in question. In Alzheimer's disease, hyperphosphorylation of the tau protein is a characteristic feature and thus a comprehensive characterization of the phosphoproteome of the CSF may be pursued to obtain a complete picture of phosphorylation aberrations in health and disease. Toward that goal we here describe a method for a comprehensive isolation and identification of phosphorylated tryptic peptides derived from CSF proteins using a simple sample preparation step and titanium dioxide-affinity chromatography followed by MALDI-TOF or LC-MS/MS linear ion-trap-FT mass spectrometry. Whereas not all previously reported phosphoproteins were found in normal CSF, we detected 56 putative novel phosphorylation sites in 38 proteins in addition to known sites. The approach seems to be a promising foundation for the discovery of new biomarkers embedded in the CSF phosphoproteome. PMID:18702456

Bahl, Justyna Maria Czarna; Jensen, Søren Skov; Larsen, Martin R; Heegaard, Niels H H

2008-08-15

363

Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis.  

PubMed

Cytokines and chemokines contribute to the pathogenesis of acute disseminated encephalomyelitis (ADEM). Using a multiplex immunochemiluminescence ELISA, we measured 8 Th1/Th2 cytokines and 18 chemokines in the cerebrospinal fluid (CSF) and serum of 17 ADEM patients, 14 multiple sclerosis (MS) patients, and 7 healthy controls (HCs). Relative to HCs, ADEM patients had significantly high mean CSF concentrations of chemokines with attractant/activating properties towards neutrophils (CXCL1 and CXCL7), monocytes/T cells (CCL3 and CCL5), Th1 cells (CXCL10), and Th2 cells (CCL1, CCL22, and CCL17). Mean CSF concentrations of CXCL7, CCL1, CCL22, and CCL17 were higher in ADEM than in MS, whereas those of CCL11 were lower in MS than in ADEM and HCs. CSF pleocytosis correlated with CSF concentrations of CXCL1, CXCL10, CCL1, CCL17, and CCL22. Most of the functionally homologous chemokines correlated with each other. CSF Th1/Th2 cytokines were not detectable in most samples. Their mean concentrations did not differ in the three groups, and the same held for serum cytokines and chemokines. Our data suggest that the upregulation of chemokines active on neutrophils and Th2 cells differentiates ADEM from MS inflammation, and that both Th1 and Th2 chemokines might be produced in ADEM. Chemokines upregulated in ADEM could become CSF biomarkers after a posteriori evaluations in unselected case series. PMID:16784758

Franciotta, Diego; Zardini, Elisabetta; Ravaglia, Sabrina; Piccolo, Giovanni; Andreoni, Laura; Bergamaschi, Roberto; Romani, Alfredo; Tavazzi, Eleonora; Naldi, Paola; Ceroni, Mauro; Marchioni, Enrico

2006-09-25

364

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

PubMed Central

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

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

2013-01-01

365

Recurrent anaplastic medulloblastoma in cerebrospinal fluid after autologous hematopoietic stem cell transplant.  

PubMed

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. PMID:22550044

Nelson, Andrew C; Singh, Charanjeet; Brent Clark, H; Pambuccian, Stefan E

2013-11-01

366

Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children  

PubMed Central

Background Cerebrospinal fluid (CSF) lactate is a potential biomarker for bacterial meningitis in children. To this end, we performed a single-center retrospective cohort study of children from Sao Paulo, Brazil, with CSF pleocytosis to evaluate the ability of CSF lactate to distinguish between children with bacterial and aseptic meningitis. We determined the optimum cutoff point for CSF lactate using receiver-operator curve (ROC) analysis. Findings We identified 451 children of whom 40 (9%) had bacterial meningitis. Children with bacterial meningitis had a higher median CSF lactate level [9.6 mmol/l, interquartile range (IQR) 3.2-38.5 mmol/l bacterial meningitis vs. 2.0 mmol/l, IQR 1.2-2.8 mmol/l aseptic meningitis]. A CSF lactate cutoff point of 3.0 mmol/l had a sensitivity of 95% [95% confidence interval (CI) 83-99%), specificity of 94% (95% CI 90-96%) and negative predictive value of 99.3% (95% CI 97.7-99.9%) for bacterial meningitis. Conclusions In combination with a validated meningitis clinical prediction rule, the CSF lactate level can be used to distinguish between bacterial and aseptic meningitis in children with CSF pleocytosis.

2014-01-01

367

[Detection of oligoclonal immunoglobulins in the cerebrospinal fluid using agar gel immunoelectrophoresis with silver salt staining].  

PubMed

Detection of oligoclonal immunoglobulins in multiple sclerosis cerebrospinal fluid (MS-CSF) seems to be an important test in the biological diagnosis of the disease. In our laboratory, the classical agarose gel electrophoretic technic allowed the detection of CSF oligoclonal bands in only 40% of the MS patients. This relatively low percentage in comparison with those obtained by other investigators led us to develop a much more resolving electrophoretic technic: an agarose gel isoelectric focusing (IEF) with silver staining. By this method, we detected oligoclonal immunoglobulins in 43 (43%) of 100 MS-CSF exhibiting only polyclonal patterns on classical electrophoresis. Oligoclonal banding appeared particularly in patients with inflammatory type profile (36/60) according to Schuller's classification, but also in those with normal (5/26) or inflammatory transudative (2/8) type profiles. MS-CSF with oligoclonal immunoglobulins on IEF had a higher IgG/Albumin ratio (p = 0.01) than those with polyclonal immunoglobulins, while the mean IgG levels were not significantly different (p = 0.07). These results support the diagnostic usefulness of the IgG/Albumin ratio. Agarose IEF appears to be a useful technic in the detection of oligoclonal immunoglobulins and may be applied at least to CSF of patients with clinical signs of multiple sclerosis. PMID:2484975

Merahba, H; Allal, C; Ghaffor, M; Rabhi, H; Abbadi, M C

1989-01-01

368

Targeted human cerebrospinal fluid proteomics for the validation of multiple Alzheimer's disease biomarker candidates  

PubMed Central

There is significant interest in the development of methods to validate novel biomarkers for Alzheimer’s disease (AD) diagnosis. Previously, a proteomic panel of cerebrospinal fluid (CSF) biomarker candidates that differentiated AD and non-AD CSF with accuracy higher than 90% was found; information about these CSF proteins can be used to develop multiple reaction monitoring (MRM) based analytical assays, which offer the possibility of quantifying protein expression level changes in samples, as well as, validation among multiple laboratories. Here we report an MRM assay that demonstrates good linearity (average R2 = 0.969) and reproducibility (average coefficient of variance of 6.93%) for the proposed AD CSF biomarkers. MRM quantification results of A?1-40, A?1-42, retinol-binding protein and cystatin C correlated well with those from ELISA (average R2 = 0.974). Analysis shows that 12 out of 16 selected targets exhibit the same trend in protein expression as that in literature.

Choi, Yong Seok; Hou, Shuyu; Choe, Leila H.; Lee, Kelvin H.

2013-01-01

369

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in Alzheimer's disease.  

PubMed

Neuron-specific enolase (NSE) is a neuronal glycolytic enzyme of which cerebrospinal fluid (CSF) levels are found altered following acute or prolonged neuronal damage. Investigations concerning the role of NSE in Alzheimer's disease (AD) are conflicting with both elevated and reduced levels. We measured CSF-levels of NSE in 32 patients with AD and 32 healthy subjects (HS) using an electrochemiluminescence immunoassay (ECLIA). Mean levels of adjusted NSE were significantly elevated in AD (18.12ng/mL (95% CI 15.63-20.60), HS 8.46ng/mL (95% CI 5.98-10.94), p=0.00002) and effect size for mean group differences high (1.84). NSE alone (cut-off score 15.80ng/mL, 94% sensitivity, 97% specificity) and in combination with T-tau and P-Tau had high diagnostic accuracy to differentiate AD from HS. NSE correlated significantly with T-tau (r?0.87, p<0.000001) and P-tau (r?0.88, p<0.000001) in both AD and HS. Our results indicate elevated CSF-NSE levels to reflect altered neuronal metabolism in AD that may be used in supporting AD diagnostics. PMID:24746933

Schmidt, Frank Martin; Mergl, Roland; Stach, Barbara; Jahn, Ina; Gertz, Hermann-Josef; Schönknecht, Peter

2014-06-01

370

Kynurenic Acid Levels in Cerebrospinal Fluid from Patients with Alzheimer's Disease or Dementia with Lewy Bodies  

PubMed Central

Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB.

Wennstrom, Malin; Nielsen, Henrietta M; Orhan, Funda; Londos, Elisabet; Minthon, Lennart; Erhardt, Sophie

2014-01-01

371

Dosimetric model for antibody targeted radionuclide therapy of tumor cells in cerebrospinal fluid  

SciTech Connect

Although encouraging results have been obtained using systemic radioimmunotherapy in the treatment of cancer, it is likely that regional applications may prove more effective. One such strategy is the treatment of central nervous system leukemia in children by intrathecal instillation of targeting or nontargeting beta particle emitting radionuclide carriers. The beta particle dosimetry of the spine is assessed, assuming that the spinal cord and the cerebrospinal fluid compartment can be adequately represented by a cylindrical annulus. The radionuclides investigated were {sup 90}Y, {sup 131}I, {sup 67}Cu, and {sup 199}Au. It is shown that the radiation dose to the cord can be significantly reduced using short range beta particle emitters and that there is little advantage in using targeting carriers with these radionuclides. {sup 199}Au and {sup 67}Cu also have the advantage of having a suitable gamma emission for imaging, permitting pretherapy imaging and dosimetric calculations to be undertaken prior to therapy. If these methods prove successful, it may be possible to replace the external beam component used in the treatment of central nervous system leukemia in children by intrathecal radionuclide therapy, thus reducing or avoiding side effects such as growth and intellectual impairment.

Millar, W.T.; Barrett, A. (Univ. of Glasgow, Scotland (England))

1990-02-01

372

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.

1988-05-01

373

Histoenzymic studies in the myelinopathy provoked by the cerebrospinal fluid exchange.  

PubMed

A histochemical study was performed on the activity of several phosphatases, esterases and oxidoreductases in the spinal cord of cat in the course of the myelinopathy provoked by the cerebrospinal fluid (CSF) exchange. The following results were obtained: 1. Neuroglial cells of the spinal cord react with a slight, focal increase of TPP-ase activity already during the early stage of myelinopathy evoked by repeated withdrawal and reinjecting of CSF into the Cisterna magna of experimental cats. 2. During the late stage of this experimental disease-- the oligo-and astroglia of the spinal cord dtsplay considerably increased activities of ATP-ase, acP, and of various oxidoreductases. 3. The observed morphological and functional (increased enzymic activity) changes of the oligodendroglia as well as the demonstrable damage of myelin sheath, seem to be the results of vasogenous edema. 4. The results of investigations performed did not yield any arguments, which would speak in favour of the assumption, that the changes of the oligodendroglia cells function as the primary cause in the myelinopathy provoked by the CSF exchange, affecting secondary the myelin sheaths. 5. The decissively increased lysosomal acP activity in oligodendroglial cells of the spinal cord investigated during the early stage of this myelinopathy, accompanied by an evidently damaged Golgi apparatus, may be explained when the Golgi zone is not necessarily the only cellular site where acid phosphatase may be performed. PMID:404827

Wender, M; Kozik, M; Goncerzewicz, A

1977-01-01

374

Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.  

PubMed

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

2013-12-01

375

Automated microparticle enzyme immunoassay for neural thread protein in cerebrospinal fluid from Alzheimer's disease patients.  

PubMed

An automated microparticle enzyme immunoassay (MEIA) with the IMx analyzer for the detection of neural thread protein (NTP) in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients was developed. This assay uses monoclonal antibodies produced against the purified pancreatic form of the protein. The assay employs one monoclonal antibody covalently coupled to the microparticle to capture immunoreactive material in CSF or brain tissue. The second monoclonal antibody was conjugated to alkaline phosphatase and serves as detection antibody. The assay provides results in approximately 45 minutes with a sensitivity of 60 pg/ml (3 fmoles/ml). The titration curve of both normal and AD CSF resulted in a linear relationship with respect to the volume of CSF used. A similar relationship was observed when normal and AD brain tissue extracts were serially diluted. The molecular weight of NTP in CSF was approximately 20 kD as determined by gel filtration method under non-denaturing conditions. The recovery for pancreatic thread protein (PTP) spiked in either normal or AD CSF was 104% and 108%, respectively. Intra-, inter-, and total assay CVs (coefficient of variation) for controls were less than 2.9%, 3.3% and 3.0%, respectively. This assay will provide a useful tool in the study of the Alzheimer's disease and may help research in diagnosis and prognosis of Alzheimer's disease and related disorders. PMID:1432364

Chong, J K; Cantrell, L; Husain, M; Riesing, S; Miller, B E; Wands, J; de la Monte, S; Ghanbari, H A

1992-01-01

376

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

2012-01-01

377

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.

2012-01-01

378

Cerebrospinal fluid and plasma leptin measurements: covariability with dopamine and cortisol in fasting humans.  

PubMed

Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites, beta-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed. PMID:10522999

Hagan, M M; Havel, P J; Seeley, R J; Woods, S C; Ekhator, N N; Baker, D G; Hill, K K; Wortman, M D; Miller, A H; Gingerich, R L; Geracioti, T D

1999-10-01

379

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

PubMed Central

There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of ?-endorphin (?-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of ?-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose ?-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of ?-END, independence of peripheral versus central levels, central ?-END migration over considerable distances, behavioral effects of ?-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain.

2012-01-01

380

HIV Migration Between Blood and Cerebrospinal Fluid or Semen Over Time.  

PubMed

Previous studies reported associations between neuropathogenesis and human immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF) and between sexual transmission and human immunodeficiency virus type 1 (HIV) compartmentalization in semen. It remains unclear, however, how compartmentalization dynamics change over time. To address this, we used statistical methods and Bayesian phylogenetic approaches to reconstruct temporal dynamics of HIV migration between blood and CSF and between blood and the male genital tract. We investigated 11 HIV-infected individuals with paired semen and blood samples and 4 individuals with paired CSF and blood samples. Aligned partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral compartmentalization, using tree-based and distance-based methods; and (3) analysis of migration events, using a discrete Bayesian asymmetric phylogeographic approach of diffusion with Markov jump counts estimation. Finally, we evaluated potential correlates of viral gene flow across anatomical compartments. We observed bidirectional replenishment of viral compartments and asynchronous peaks of viral migration from and to blood over time, suggesting that disruption of viral compartment is transient and directionally selected. These findings imply that viral subpopulations in anatomical sites are an active part of the whole viral population and that compartmental reservoirs could have implications in future eradication studies. PMID:24302756

Chaillon, Antoine; Gianella, Sara; Wertheim, Joel O; Richman, Douglas D; Mehta, Sanjay R; Smith, David M

2014-05-01

381

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

2012-01-01

382

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.

2011-01-01

383

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

2008-01-01

384

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

PubMed

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

2001-04-25

385

A fast and reproducible method for albumin isolation and depletion from serum and cerebrospinal fluid.  

PubMed

Analysis of serum and plasma proteomes is a common approach for biomarker discovery, and the removal of high-abundant proteins, such as albumin and immunoglobins, is usually the first step in the analysis. However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker subproteome itself. The first goal of this study was to test a new commercially available affinity capture reagent from Protea Biosciences and to compare the efficiency and reproducibility to four other commercially available albumin depletion methods. The second goal of this study was to determine if there is a highly efficient albumin depletion/isolation system that minimizes sample handling and would be suitable for large numbers of samples. Two of the methods tested (Sigma and ProteaPrep) showed an albumin depletion efficiency of 97% or greater for both serum and cerebrospinal fluid (CSF). Isolated serum and CSF albuminomes from ProteaPrep spin columns were analyzed directly by LC-MS/MS, identifying 128 serum (45 not previously reported) and 94 CSF albuminome proteins (17 unique to the CSF albuminome). Serum albuminome was also isolated using Vivapure anti-HSA columns for comparison, identifying 105 proteins, 81 of which overlapped with the ProteaPrep method. PMID:23300121

Holewinski, Ronald J; Jin, Zhicheng; Powell, Matthew J; Maust, Matthew D; Van Eyk, Jennifer E

2013-03-01

386

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 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

Miller, B.E.; Lipman, J.J.; Byrne, W.L.

1987-12-07

387

Cerebrospinal fluid B2-microglobulin levels in meningeal involvement by malignancy.  

PubMed

Cerebrospinal fluid (CSF) and serum B2-microglobulin (B2m) levels were measured prospectively in 63 patients with hematological malignancies and 14 patients with solid tumours to evaluate the correlation between elevated levels and malignant infiltration of meninges. Serial CSF B2-m levels were also measured in 18 patients who received prophylactic intrathecal cytotoxic treatment. CSF B2-m levels were significantly higher in patients with central nervous system (CNS) involvement than in those without (p less than 0.001). A CSF B2-m level greater than 1.80 mg/L was closely associated with CNS disease (specificity 96%, sensitivity 76%) and CNS infiltration was also likely when the CSF B2-m level exceeded a simultaneously drawn serum level (specificity 98%, sensitivity 46%). Intrathecal methotrexate prophylaxis resulted in a consistent and significant rise in CSF B2-m levels with an average increase of 96% during a course of intrathecal injections. These results suggest that CSF B2-m levels may not be helpful for predicting early CNS relapse in these patients. However the CSF B2-m level and the corresponding serum B2-m level is a useful adjunct to the cytological diagnosis of CNS involvement by malignancy at presentation. Its value in predicting early CNS relapse and documenting response to CNS treatment requires further clarification. PMID:2194155

Jeffery, G M; Frampton, C M; Legge, H M; Hart, D N

1990-01-01

388

Age-Specific Characteristics and Coupling of Cerebral Arterial Inflow and Cerebrospinal Fluid Dynamics  

PubMed Central

The objective of this work is to quantify age-related differences in the characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid (CSF) dynamics. To this end, 3T phase-contrast magnetic resonance imaging blood and CSF flow data of eleven young ( years) and eleven elderly subjects ( years) with a comparable sex-ratio were acquired. Flow waveforms and their frequency composition, transfer functions from blood to CSF flows and cross-correlations were analyzed. The magnitudes of the frequency components of CSF flow in the aqueduct differ significantly between the two age groups, as do the frequency components of the cervical spinal CSF and the arterial flows. The males' aqueductal CSF stroke volumes and average flow rates are significantly higher than those of the females. Transfer functions and cross-correlations between arterial blood and CSF flow reveal significant age-dependence of phase-shift between these, as do the waveforms of arterial blood, as well as cervical-spinal and aqueductal CSF flows. These findings accentuate the need for age- and sex-matched control groups for the evaluation of cerebral pathologies such as hydrocephalus.

Schmid Daners, Marianne; Knobloch, Verena; Soellinger, Michaela; Boesiger, Peter; Seifert, Burkhardt; Guzzella, Lino; Kurtcuoglu, Vartan

2012-01-01

389

Protein determination in cerebrospinal fluid by protein dye-binding assay.  

PubMed

In this study, Coomassie brilliant blue (CBB) and pyrogallol red/molybdate (PRM) protein dye-binding assays for total protein determination in cerebrospinal fluid (CSF) are compared. Using human albumin (HA) as a protein calibrator, protein concentration in CSF samples (n = 73) ranged from 55-1960 mg/L (median: 315 mg/L) with the CBB assay, and from 95-2450 mg/L (median: 395 mg/L) with the PRM assay. Linear regression analysis indicated yCBB = 0.824xPRM - 8 (r = 0.99). The discrepancy between the values was investigated by comparing the response of the two assays to different proteins. Compared with HA, the PRM assay showed a more uniform response to human albumin/globulin (A/G) and bovine gamma globulin (G) than did the CBB assay, but it gave high colour yields with bovine myelin basic protein. When CSF was assayed using A/G as a protein calibrator, agreement between the methods improved (yCBB = 0.960xPRM + 0 [r = 0.99]), indicating that comparability is dictated by the choice of protein calibrator. Of the two assays studied, the PRM assay is recommended for CSF protein determination because it gives a more uniform and linear response to human albumin and globulin over a wider working range. PMID:11204856

Marshall, T; Williams, K M

2000-01-01

390

Cerebrospinal fluid glutamate concentration correlates with impulsive aggression in human subjects  

PubMed Central

Neurochemical studies have pointed to a modulatory role in human aggression for various central neurotransmitters. Some (e.g., serotonin) appear to play an inhibitory role, while others appear to play a facilitator role. While recent animal studies of glutaminergic activity suggest a facilitator role for central glutamate in the modulation of aggression, no human studies of central glutaminergic indices have yet been reported regarding aggression. Basal lumbar cerebrospinal fluid (CSF) was obtained from 38 physically healthy subjects with DSM-IV Personality Disorder (PD: n = 28) and from Healthy Volunteers (HV: n = 10) and assayed for glutamate, and other neurotransmitters, in CSF and correlated with measures of aggression and impulsivity. CSF Glutamate levels did not differ between the PD and HC subjects but did directly correlate with composite measures of both aggression and impulsivity and a composite measure of impulsive aggression in both groups. These data suggest a positive relationship between CSF Glutamate levels and measures of impulsive aggression in human subjects. Thus, glutamate function may contribute to the complex central neuromodulation of impulsive aggression in human subjects.

Coccaro, Emil F.; Lee, Royce; Vezina, Paul

2014-01-01

391

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

SciTech Connect

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

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

2013-12-13

392

The characterization of arachnoid cell transport II: paracellular transport and blood-cerebrospinal fluid barrier formation.  

PubMed

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

2012-10-11

393

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

2013-01-01

394

Ceruloplasmin is increased in cerebrospinal fluid in Alzheimer's disease but not Parkinson's disease.  

PubMed

Although the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD) is unknown, altered brain antioxidative mechanisms have been found in both disorders. Ceruloplasmin (CP) and transferrin (TF) interact to limit concentrations of free ferrous iron (Fe2+), and thus play an important role in antioxidant defense in serum; both proteins are also produced in brain, where their significance as antioxidants is unknown. We quantified concentrations of CP and TF by immunoassay in AD (n = 17) and PD (n = 12) cerebrospinal fluid (CSF) to determine whether these proteins could serve as disease markers. CP was increased versus aged normal subjects (n = 11) in AD (p < 0.05) but not PD CSF, whereas TF concentrations did not differ between groups. CP levels have been reported to be elevated in some brain regions in AD, and increased CP in AD CSF may reflect this finding. Systemic inflammation and oxidative stress are major factors stimulating hepatic CP synthesis, and it remains to be determined whether increased CP concentrations in AD CSF and brain follow from similar mechanisms. PMID:7986488

Loeffler, D A; DeMaggio, A J; Juneau, P L; Brickman, C M; Mashour, G A; Finkelman, J H; Pomara, N; LeWitt, P A

1994-01-01

395

Cerebrospinal Fluid Biomarkers for Major Depression Confirm Relevance of Associated Pathophysiology  

PubMed Central

Individual characteristics of pathophysiology and course of depressive episodes are at present not considered in diagnostics. There are no biological markers available that can assist in categorizing subtypes of depression and detecting molecular variances related to disease-causing mechanisms between depressed patients. Identification of such differences is important to create patient subgroups, which will benefit from medications that specifically target the pathophysiology underlying their clinical condition. To detect characteristic biological markers for major depression, we analyzed the cerebrospinal fluid (CSF) proteome of depressed vs control persons, using two-dimensional polyacrylamide gel electrophoresis and time-of-flight (TOF) mass spectrometry peptide profiling. Proteins of interest were identified by matrix-assisted laser desorption ionization TOF mass spectrometry (MALDI-TOF-MS). Validation of protein markers was performed by immunoblotting. We found 11 proteins and 144 peptide features that differed significantly between CSF from depressed patients and controls. In addition, we detected differences in the phosphorylation pattern of several CSF proteins. A subset of the differentially expressed proteins implicated in brain metabolism or central nervous system disease was validated by immunoblotting. The identified proteins are involved in neuroprotection and neuronal development, sleep regulation, and amyloid plaque deposition in the aging brain. This is one of the first hypothesis-free studies that identify characteristic protein expression differences in CSF of depressed patients. Proteomic approaches represent a powerful tool for the identification of disease markers for subgroups of patients with major depression.

Ditzen, Claudia; Tang, Ning; Jastorff, Archana M; Teplytska, Larysa; Yassouridis, Alexander; Maccarrone, Giuseppina; Uhr, Manfred; Bronisch, Thomas; Miller, Christine A; Holsboer, Florian; Turck, Christoph W

2012-01-01

396

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?

2013-01-01

397

Inductively coupled microfluidic pressure meter for in vivo monitoring of cerebrospinal fluid shunt function.  

PubMed

A microfluidic pressure sensor with inductively coupled, wireless readout capability has been developed for integration into cerebrospinal fluid shunt valve implants. The sensor consists of a deformable PDMS film that is bonded over a microfluidic reservoir, forming a fluidic capacitor. Deflection of the capacitor membrane is detected remotely through a shift in the resonance frequency of a micro-fabricated LC circuit. Sensors were fabricated by a combination of conventional MEMS technologies and rapid soft lithography. A direct pattern transfer technique was used to pattern the deformable PDMS film with a metal coating for the capacitive readout. The mechanical response of the fluidic capacitor was characterized by measuring the deflection of the PDMS film using an extrinsic Fabry-Perot interferometer (EFPI), and wireless sensing was demonstrated by the shift in resonance frequency of the sensor via an inductively coupled antenna. The sensor transduces pressure into a change in resonant frequency with sensitivity >?3.4?ppm Pa?¹ and responsivity 4.6?kHz Pa?¹, over a dynamic range of 0~3 kPa. PMID:22316101

Song, S-H; Gillies, G T; Begley, M R; Utz, M; Broaddus, W C

2012-04-01

398

Determination of leukocyte counts in cerebrospinal fluid with a disposable plastic hemocytometer.  

PubMed

Manual microscopic cell counting in a Fuchs-Rosenthal (FR) chamber has been the gold standard for quantification of leukocytes in cerebrospinal fluid (CSF). However, for accurate determination of the number and differentiation of cells by chamber counting, hemocytometers must be prepared carefully and kept clean. Improper fitting of the chamber and coverslip changes the volume of sample introduced into the chamber well. Moreover, because conventional hemocytometers are used repeatedly and are breakable, there is a risk of exposure to potentially infectious material. To address these issues, disposable plastic hemocytometers have been developed. However, the accuracy, precision, and clinical usefulness of disposable chambers for CSF cells counting have not been determined. In the present study, we evaluated use of a disposable plastic counting chamber (C-Chip DHC-F01) by comparing its performance with that of an FR chamber for counting of CSF specimens and cell suspensions. Within-run precision of C-Chip counting was comparable or superior to that of FR chamber counting, and excellent correlation between cell counts obtained with the C-Chip chamber and FR chamber was observed. However, C-Chip chambers that were kept at 4 degrees C yielded significantly low cell counts. The disposable hemocytometer will reduce the risk of exposure to potentially infectious material. However, use of C-Chip chambers should be avoided in cold environments. PMID:17847111

Yamanishi, Hachiro; Imai, Nobuko; Suehisa, Etsuji; Kanakura, Yuzuru; Iwatani, Yoshinori

2007-01-01

399

Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola.  

PubMed

Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis. PMID:22585725

Pelkonen, Tuula; Roine, Irmeli; Anjos, Elizabete; Kaijalainen, Svetlana; Roivainen, Merja; Peltola, Heikki; Pitkäranta, Anne

2012-07-01

400

Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid.  

PubMed

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor-related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids--such as cerebrospinal fluid (CSF), serum, and urine--can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG. PMID:22492959

Saratsis, Amanda M; Yadavilli, Sridevi; Magge, Suresh; Rood, Brian R; Perez, Jennifer; Hill, D Ashley; Hwang, Eugene; Kilburn, Lindsay; Packer, Roger J; Nazarian, Javad

2012-05-01

401

Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid  

PubMed Central

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor–related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids—such as cerebrospinal fluid (CSF), serum, and urine—can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG.

M. Saratsis, Amanda; Yadavilli, Sridevi; Magge, Suresh; Rood, Brian R.; Perez, Jennifer; Hill, D. Ashley; Hwang, Eugene; Kilburn, Lindsay; Packer, Roger J.; Nazarian, Javad

2012-01-01

402

Proteomic analysis of cerebrospinal fluid: toward the identification of biomarkers for gliomas.  

PubMed

Gliomas are the most common primary brain tumors in adults and, despite advances in the understandings of glioma pathogenesis in the genetic era, they are still ineradicable, justifying the need to develop more reliable diagnostic and prognostic biomarkers for this malignancy. Because changes in cerebrospinal fluid (CSF) are suggested to be capable of sensitively reflecting pathological processes, e.g., neoplastic conditions, in the central nervous system, CSF has been deemed a valuable source for potential biomarkers screening in this era of proteomics. This systematic review focused on the proteomic analysis of glioma CSF that has been published to date and identified a total of 19 differentially expressed proteins. Further functional and protein-protein interaction assessments were performed by using Protein Analysis Through Evolutionary Relationships (PANTHER) website and Ingenuity Pathway Analysis (IPA) software, which revealed several important protein networks (e.g., IL-6/STAT-3) and four novel focus proteins (IL-6, galanin (GAL), HSPA5, and WNT4) that might be involved in glioma pathogenesis. The concentrations of these focus proteins were subsequently determined by enzyme-linked immunosorbent assay (ELISA) in an independent set of CSF and tumor cyst fluid (CF) samples. Specifically, glioblastoma (GBM) CF had significantly lower GAL, HSPA5, and WNT4 levels than CSF from different grades of glioma. In contrast, IL-6 level was significantly higher in GBM CF when compared with CSF and, among different CSF groups, was highest in GBM CSF. Therefore, these candidate protein biomarkers, identified from both the literatures and in silico analysis, may have potentials in clinical diagnosis, prognosis evaluation, treatment response monitoring, and novel therapeutic targets identification for patients with glioma. PMID:24781189

Shen, Fang; Zhang, Yang; Yao, Yu; Hua, Wei; Zhang, Hai-Shi; Wu, Jing-Song; Zhong, Ping; Zhou, Liang-Fu

2014-07-01

403

Factors in cerebrospinal fluid from goats that affect sleep and activity in rats*  

PubMed Central

1. Intraventricular infusion in the rat of 0·1 ml. cerebrospinal fluid (c.s.f.) from sleep-deprived goats increases the duration of sleep (measured by e.e.g.) and decreases locomotor activity (measured photo-electrically) for at least 6 hr subsequent to the infusion. Subarachnoid infusions are ineffective. 2. C.s.f. from control and sleep-deprived goats was fractionated by ultrafiltration through molecular sieves. The sleep-promoting Factor S is found in the low molecular weight fraction (mol. wt. < 500) of c.s.f. from sleep-deprived but not from control goats. 3. The concentration of Factor S in c.s.f. increases progressively during the first 48 hr of sleep deprivation. 4. The sleep promoting effects of Factor S cannot be duplicated by serotonin, 4-OH-butyrate, butyrolactone, GABA (?-amino butyric acid), glutamic acid or 3?,5?-cyclic AMP when these substances are added to control fluids in concentrations up to 10 times greater than those found in normal c.s.f. 5. Intraventricular or subarchnoid infusion in the rat of 0·1 ml. proteinfree c.s.f. containing molecules in the mol. wt. range of 500-10,000 at 10-30 × normal concentration causes hyperactivity which persists for several days and nights following the infusion. The excitatory material, probably a peptide, is present in c.s.f. from both control and sleep-deprived goats. 6. The properties of Factor S suggest that it may play a role in the normal regulation of sleep and wakefulness.

Fencl, V.; Koski, G.; Pappenheimer, J. R.

1971-01-01

404

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

PubMed Central

Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease groups revealed that the greatest anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some MS patients had increased reactivity with the hydrophobic FMCs and with glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked.

Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B.; Tourtellotte, Wallace W.; Annuk, Heidi; Moran, Anthony P.; Hogan, Edward L.

2010-01-01

405

A coaxial tube model of the cerebrospinal fluid pulse propagation in the spinal column.  

PubMed

The dynamics of the movement of the cerebrospinal fluid (CSF) may play an important role in the genesis of pathological neurological conditions such as syringomyelia, which is characterized by the presence of a cyst (syrinx) in the spinal cord. In order to provide sound theoretical grounds for the hypotheses that attribute the formation and growth of the syrinx to impediments to the normal movement of the CSF, it is necessary to understand various modes through which CSF pulse in the spinal column propagates. Analytical models of small-amplitude wave propagation in fluid-filled coaxial tubes, where the outer tube represents dura, the inner tube represents the spinal cord, and the fluid is the CSF, have been used to that end. However, so far, the tendency was to model one of the two tubes as rigid and to neglect the effect of finite thickness of the tube walls. The aim of this study is to extend the analysis in order to address these two potentially important issues. To that end, classical linear small-amplitude analysis of wave propagation was applied to a system consisting of coaxial tubes of finite thickness filled with inviscid incompressible fluid. General solutions to the governing equations for the case of harmonic waves in the long wave limit were replaced with the boundary conditions to yield the characteristic (dispersion) equation for the system. The four roots of the characteristic equation correspond to four modes of wave propagation, of which the first three are associated with significant motion of the CSF. For the normal range of parameters the speeds of the four modes are c(1)=13 ms, c(2)=14.7 ms, c(3)=30.3 ms, and c(4)=124.5 ms, which are well within the range of values previously reported in experimental and theoretical studies. The modes with the highest and the lowest speeds of propagation can be attributed to the dura and the spinal cord, respectively, whereas the remaining two modes involve some degree of coupling between the two. When the thickness of the spinal cord, is reduced below its normal value, the first mode becomes dominant in terms of the movement of the CSF, and its speed drops significantly. This suggests that the syrinx may be characterized by an abnormally low speed of the CSF pulse. PMID:19102567

Cirovic, Srdjan

2009-02-01

406

Computational fluid dynamics modelling of cerebrospinal fluid pressure in Chiari malformation and syringomyelia.  

PubMed

The pathogenesis of syringomyelia in association with Chiari malformation (CM) is unclear. Studies of patients with CM have shown alterations in the CSF velocity profile and these could contribute to syrinx development or enlargement. Few studies have considered the fluid mechanics of CM patients with and without syringomyelia separately. Three subject-specific CFD models were developed for a normal participant, a CM patient with syringomyelia and a CM patient without syringomyelia. Model geometries, CSF flow rate data and CSF velocity validation data were collected from MRI scans of the 3 subjects. The predicted peak CSF pressure was compared for the 3 models. An extension of the study performed geometry and flow substitution to investigate the relative effects of anatomy and CSF flow profile on resulting spinal CSF pressure. Based on 50 monitoring locations for each of the models, the CM models had significantly higher magnitude (p<0.01) peak CSF pressure compared with normal. When using the same CSF input flow waveform, changing the upper spinal geometry changed the magnitude of the CSF pressure gradient, and when using the same upper spinal geometry, changing the input flow waveform changed the timing of the peak pressure. This study may assist in understanding syringomyelia mechanisms and relative effects of CSF velocity profile and spinal geometry on CSF pressure. PMID:23769174

Clarke, Elizabeth C; Fletcher, David F; Stoodley, Marcus A; Bilston, Lynne E

2013-07-26

407

Diabetic Retinopathy and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011  

PubMed Central

Purpose The cerebrospinal fluid pressure (CSFP) is a major determinant of central retinal vein pressure and thus of retinal capillary pressure. We tested the hypothesis whether prevalence and severity of diabetic retinopathy are associated with CSFP. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. A detailed ophthalmic examination was performed including fundus photography for the assessment of diabetic retinopathy according. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg]?=?0.44xBody Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]–0.18xAge[Years]?1.91. Results In binary regression analysis, presence of diabetic retinopathy was significantly associated with higher levels of HbA1c (P<0.001; regression coefficient B:0.25; odds ratio (OR):1.28; 95% confidence interval (CI):1.15,1.43), higher blood concentration of glucose (P<0.001; B:0.40;OR:1.49;95%CI:1.36,1.63), longer known duration of diabetes mellitus (P<0.001; B:0.14;OR:1.15; 95%CI:1.11,1.19), higher systolic blood pressure (P<0.001; B:0.03;OR:1.03;95%CI:1.02,1.04), lower diastolic blood pressure (P<0.001; B:?0.06;OR:0.94;95%CI:0.91,0.97), and higher CSFP (P?=?0.002; B:0.13;OR:1.14;95%CI:1.05,1.24). Severity of diabetic retinopathy was significantly associated with higher HbA1c value (P<0.001; standardized coefficient beta: 0.19; correlation coefficient B: 0.07;95%CI:0.05,0.08), higher blood concentration of glucose (P<0.001; beta:0.18;B:0.04;95%CI:0.04,0.05), longer known duration of diabetes mellitus (P<0.001; beta:0.20;B:0.03;95%CI:0.02,0.03), lower level of education (P?=?0.001; beta:?0.05;B:?0.02;95%CI:?0.03,?0.01), lower diastolic blood pressure (P?=?0.002; beta:?0.08;B:?0.001;95%CI:?0.004,?0.001), higher systolic blood pressure (P?=?0.006; beta:0.06;B:0.001;95%CI:0.000,0.001), and higher CSFP (P?=?0.006; beta:0.06;B:0.006;95%CI:0.002,0.010). Conclusions Higher prevalence and severity of diabetic retinopathy were associated with higher estimated CSFP after adjusting for systemic parameters. Higher CSFP through a higher retinal vein pressure may lead to more marked retinal venous congestion and vascular leakage in diabetic retinae.

Wang, Ya Xing; You, Qi Sheng; Yang, Diya; Xie, Xiao Bin; Xu, Liang

2014-01-01

408

Morphological estimation of brain extracellular fluid dynamics in cold-induced edema from the aspect of cerebrospinal fluid-extracellular fluid communication.  

PubMed

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3-4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3-4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution. PMID:2392933

Hattori, H; Kimura, M; Takahashi, M; Hashimoto, S

1990-05-01

409

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease  

PubMed Central

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion

Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

2008-01-01

410

Proteomic analysis of the cerebrospinal fluid in multiple sclerosis and neuromyelitis optica patients.  

PubMed

The present study aimed to compare the 2-dimensional (2D) electrophoresis pattern of the cerebrospinal fluid (CSF) in multiple sclerosis (MS), neuromyelitis optica (NMO) and control individuals, to identify the proteins with differential expression and to examine their significance. CSF samples from the three groups were collected and total protein was isolated and quantified using the Bradford method. 2D electrophoresis of the samples was conducted using equal amounts of CSF. In the CSF 2D gel electrophoresis map, 118 points were obtained from the MS group, 155 points from the NMO group and 350 points from the normal control group. Non-matching proteins appeared in 14 spots in the MS group and in 45 spots in the NMO group, and were also expressed in the 2D electrophoresis pattern of the normal control group. Four differential proteins were identified through the HD-MS/MS and MASCOT network search. Pre-albumin (PA) was found only in the CSF 2D gel electrophoresis map of the MS patients. Keratin 1 was expressed in the normal control group, but not in the MS group. The difference in the expression of keratin 9 in the MS group was twice that in the normal control group. The expression of keratin 1, keratin 9 and transferrin in the NMO group was twice that in the normal control group. The expression of PA was found only in the CSF 2D gel electrophoresis map of the MS patients, and not in the NMO group. Keratin 1 was expressed in the NMO group, but not in the MS group. The expression of a variety of proteins in the 2D electrophoresis pattern of CSF was significantly different in the MS, NMO and control groups. PA, keratin 1, transferrin and keratin 9 are identified as significantly differentially expressed proteins. PMID:22895575

Jiang, Shoufeng; Wu, Jiong; Yang, Yi; Liu, Jianren; Ding, Yao; Ding, Meiping

2012-11-01

411

Analysis of Risk Factors and Management of Cerebrospinal Fluid Morbidity in the Treatment of Spinal Dysraphism  

PubMed Central

Objective Spinal dysraphism defects span wide spectrum. Wound dehiscence is a common postoperative complication, and is a challenge in the current management of cerebrospinal fluid (CSF) leaks and wound healing. The purpose of this study is to evaluate the risks of CSF-related morbidity in the surgical treatment of spinal dysraphism. Methods Ten patients with spinal dysraphism were included in this retrospective study. The median age of the cohort was 4.8 months. To assess the risk of CSF morbidity, we measured the skin lesion area and the percentage of the skin lesion area relative to the back surface for each patient. We then analyzed the relationship between morbidity and the measured skin lesion area or related factors. Results The overall median skin lesion area was 36.2 cm2 (n=10). The percentage of the skin lesion area relative to the back surface ranged from 0.6% to 18.1%. During surgical reconstruction, 4 patients required subsequent operations to repair CSF morbidity. The comparison of the mean area of skin lesions between the CSF morbidity group and the non-CSF morbidity group was statistically significant (average volume skin lesion of 64.4±32.5 cm2 versus 27.7±27.8 cm2, p<0.05). CSF morbidity tended to occur either when the skin lesion area was up to 44.2 cm2 or there was preexisting fibrosis before revision with an accompanying broad-based dural defect. Conclusion Measuring the lesion area, including the skin, dura, and related surgical parameters, offers useful information for predicting wound challenges and selecting appropriate reconstructive surgery methods.

Lee, Byung-Jou; Han, Seong-Rok; Choi, Chan-Young; Lee, Dong-Joon; Kang, Jae Heon

2013-01-01

412

The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid.  

PubMed

Streptococcus suis (SS) is an important pathogen of pigs, and it is also recognized as a zoonotic agent for humans. SS infection may result in septicemia or meningitis in the host. However, little is known about genes that contribute to the virulence process and survival within host blood or cerebrospinal fluid (CSF). Small RNAs (sRNA) have emerged as key regulators of virulence in several bacteria, but they have not been investigated in SS. Here, using a differential RNA-sequencing approach and RNAs from SS strain P1/7 grown in rich medium, pig blood, or CSF, we present the SS genome-wide map of 793 transcriptional start sites and 370 operons. In addition to identifying 29 sRNAs, we show that five sRNA deletion mutants attenuate SS virulence in a zebrafish infection model. Homology searches revealed that 10 sRNAs were predicted to be present in other pathogenic Streptococcus species. Compared with wild-type strain P1/7, sRNAs rss03, rss05, and rss06 deletion mutants were significantly more sensitive to killing by pig blood. It is possible that rss06 contributes to SS virulence by indirectly activating expression of SSU0308, a virulence gene encoding a zinc-binding lipoprotein. In blood, genes involved in the synthesis of capsular polysaccharide (CPS) and subversion of host defenses were up-regulated. In contrast, in CSF, genes for CPS synthesis were down-regulated. Our study is the first analysis of SS sRNAs involved in virulence and has both improved our understanding of SS pathogenesis and increased the number of sRNAs known to play definitive roles in bacterial virulence. PMID:24759092

Wu, Zongfu; Wu, Chunyan; Shao, Jing; Zhu, Zhenzhen; Wang, Weixue; Zhang, Wenwei; Tang, Min; Pei, Na; Fan, Hongjie; Li, Jiguang; Yao, Huochun; Gu, Hongwei; Xu, Xun; Lu, Chengping

2014-06-01

413

MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid.  

PubMed

MicroRNAs (miRNAs) are small, noncoding RNAs that function in complex networks to regulate protein expression. In the brain, they are involved in development and synaptic plasticity. In this study, we aimed to identify miRNAs with a differential expression in either hippocampus or cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and age-matched nondemented control subjects using quantitative polymerase chain reaction. In hippocampus, we also differentiated between AD patients with an intermediate stage, according to Braak III/IV stage, and a late stage, characterized according to Braak VI stage. Eight selected miRNAs were analyzed in hippocampus, and the expression of miR-16, miR-34c, miR-107, miR-128a, and miR-146a were differentially regulated. In CSF, out of 8 selected miRNAs only miR-16 and miR-146a could be reliably detected. In addition, we identified an effect of blood contamination on the CSF levels of miR-16, miR-24, and miR-146a. For group comparisons, we therefore selected CSF samples absent of, or containing only low numbers of blood cells. Levels of miR-146a were significantly decreased in CSF of AD patients. In conclusion, the abnormal expression of several miRNAs in hippocampus of intermediate- and late-stage AD patients suggests their involvement in AD pathogenesis, and low levels of miR-146a in CSF were associated with AD. PMID:23962497

Müller, Mareike; Kuiperij, H Bea; Claassen, Jurgen A; Küsters, Benno; Verbeek, Marcel M

2014-01-01

414

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients.  

PubMed

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3-5, days 7-9 and days 12-14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3-5 (p=0.002) after SAH, peaked on days 7-9 (p<0.001) and remained elevated until days 12-14 (p<0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7-9 (correlation coefficient=-0.55, p=0.012; 95% confidence interval -0.80 to -0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7-9 predicted a poor clinical outcome at 2year follow-up after SAH (odds ratio=1.722, p=0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH. PMID:24814854

Li, Hua; Wu, Wei; Liu, Ming; Zhang, Xin; Zhang, Qing-Rong; Ni, Li; Hang, Chun-Hua

2014-08-01