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Sample records for cerebrospinal fluid protein

  1. Cerebrospinal fluid.

    PubMed

    Jerrard, D A; Hanna, J R; Schindelheim, G L

    2001-08-01

    A quick and accurate diagnosis of maladies affecting the central nervous system (CNS) is imperative. Procurement and analysis of cerebrospinal fluid (CSF) are paramount in helping the clinician determine a patient's clinical condition. Various staining methods, measurement of white blood cell counts, glucose and protein levels, recognition of xanthochromia, and microbiologic studies are CSF parameters that are collectively important in the ultimate determination by a clinician of the presence or absence of a catastrophic CNS condition. Many of these CNS parameters have significant limitations that should be recognized to minimize under treating patients with catastrophic illness. PMID:11489408

  2. Distinct Lysosomal Network Protein Profiles in Parkinsonian Syndrome Cerebrospinal Fluid

    PubMed Central

    Boman, Andrea; Svensson, Samuel; Boxer, Adam; Rojas, Julio C.; Seeley, William W.; Karydas, Anna; Miller, Bruce; Kågedal, Katarina; Svenningsson, Per

    2016-01-01

    Background: Clinical diagnosis of parkinsonian syndromes like Parkinson’s disease (PD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is hampered by overlapping symptomatology and lack of diagnostic biomarkers, and definitive diagnosis is only possible post-mortem. Objective: Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that profiles of select lysosomal network proteins in cerebrospinal fluid could be differentially expressed in these parkinsonian syndromes. Methods: Cerebrospinal fluid samples were collected from PD patients (n = 18), clinically diagnosed 4-repeat tauopathy patients; corticobasal syndrome (CBS) (n = 3) and PSP (n = 8); and pathologically diagnosed PSP (n = 8) and CBD patients (n = 7). Each patient set was compared to its appropriate control group consisting of age and gender matched individuals. Select lysosomal network protein levels were detected via Western blotting. Factor analysis was used to test the diagnostic sensitivity, specificity and accuracy of the select lysosomal network protein expression profiles. Results: PD, CBD and PSP were markedly different in their cerebrospinal fluid lysosomal network protein profiles. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in PD; early endosomal antigen 1 was decreased and lysozyme increased in PSP; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in CBD. A panel of lysosomal-associated membrane protein 2, lysozyme and microtubule-associated protein 1 light chain discriminated between controls, PD and 4-repeat tauopathies. Conclusions: This study offers proof of concept that select lysosomal network proteins are differentially expressed in cerebrospinal fluid of Parkinson’s disease, corticobasal syndrome and progressive supranuclear palsy. Lysosomal network protein analysis

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

    PubMed Central

    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

    The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and β-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that α-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and α-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, α-2-HS-glycoprotein, transferrin, α-1β-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption. PMID:23401751

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

    PubMed

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

    2016-08-01

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

  5. Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease.

    PubMed

    Pirttilä, T; Koivisto, K; Mehta, P D; Reinikainen, K; Kim, K S; Kilkku, O; Heinonen, E; Soininen, H; Riekkinen, P; Wisniewski, H M

    1998-06-12

    Levels of soluble amyloid beta protein (sAbeta), amyloid beta precursor protein (APP) and apolipoprotein E (apoE) were examined in cerebrospinal fluid (CSF) obtained twice, at baseline and after 3-year follow-up, from 25 patients with probable Alzheimer's disease (AD). Levels of sAbeta and apoE from patients with the apoE4 allele decreased with time, whereas the levels were similar in patients without apoE4 allele. Changes of sAbeta and apoE concentrations correlated significantly with those of mini-mental state examination (MMSE) scores. Levels of sAbeta did not change with time in patients with mild dementia, whereas they decreased significantly in patients with moderate dementia. ApoE concentrations decreased in both groups whereas APP levels were similar. We conclude that measurements of CSF sAbeta and apoE levels may be helpful in monitoring progression of the disease. PMID:9672379

  6. Multiplexed MRM with Internal Standards for Cerebrospinal Fluid Candidate Protein Biomarker Quantitation.

    PubMed

    Percy, Andrew J; Yang, Juncong; Chambers, Andrew G; Simon, Romain; Hardie, Darryl B; Borchers, Christoph H

    2014-06-30

    Multiplexed quantitation is essential for discovering, verifying, and validating biomarkers for risk stratification, disease prognostication, and therapeutic monitoring. The most promising strategy for quantifying unverified protein biomarkers in biofluids relies on selected/multiple reaction monitoring (SRM or MRM) technology with isotopically labeled standards employed within a bottom-up proteomic workflow. Since cerebrospinal fluid (CSF) is an important fluid for studying central nervous system (CNS) related diseases, we sought to develop a rapid, antibody- and fractionation-free MRM-based approach with a complex mixture of peptide standards to quantify a highly multiplexed panel of candidate protein biomarkers in human CSF. Development involved peptide transition optimization, denaturation/digestion protocol evaluation, transition interference screening, and protein quantitation via peptide standard curves. The final method exhibited excellent reproducibility (average coefficient of variation of <1% for retention time and <6% for signal) and breadth of quantitation (130 proteins from 311 interference-free peptides) in a single 43-min run. These proteins are of high-to-low abundance with determined concentrations from 118 μg/mL (serum albumin) to 550 pg/mL (apolipoprotein C-I). Overall, the method consists of the most highly multiplexed and broadest panel of candidate protein biomarkers in human CSF reported thus far and is well suited for subsequent verification studies on patient samples. PMID:24911472

  7. Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease.

    PubMed

    Fang, Qiaojun; Strand, Andrew; Law, Wendy; Faca, Vitor M; Fitzgibbon, Matthew P; Hamel, Nathalie; Houle, Benoit; Liu, Xin; May, Damon H; Poschmann, Gereon; Roy, Line; Stühler, Kai; Ying, Wantao; Zhang, Jiyang; Zheng, Zhaobin; Bergeron, John J M; Hanash, Sam; He, Fuchu; Leavitt, Blair R; Meyer, Helmut E; Qian, Xiaohong; McIntosh, Martin W

    2009-03-01

    We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brain-specific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins. PMID:18984577

  8. Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein

    PubMed Central

    Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

    2015-01-01

    Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1–4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis. PMID:26509880

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

    PubMed

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

    2013-02-01

    The axonal cytoskeleton is a finely organized system, essential for maintaining the integrity of the axon. Axonal degeneration is implicated in the pathogenesis of unremitting disability of multiple sclerosis (MS). Purpose of this study is to evaluate levels of cytoskeletal proteins such as neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), and β-tubulin (β-Tub) isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their correlation with MS clinical indices. CSF levels of cytoskeletal proteins were determined in 51 patients: 33 with MS and 18 with other neurological diseases (OND). NFL, GFAP and β-Tub II proteins were significantly higher (p < 0.0001) in MS than in OND group; no significant difference (p > 0.05) was found between MS and OND with regard to β-Tub III. Interestingly, levels of β-Tub III and NFL were higher in progressive than in remitting MS forms; on the contrary, higher levels of β-Tub II and GFAP were found in remitting MS forms. However, with the exception of β-Tub III, all proteins tend to decrease their CSF levels concomitantly with the increasing disability (EDSS) score. Overall, our results might indicate β-Tub II as a potential candidate for diagnostic and β-Tub III as a possible prognostic biomarker of MS. Therefore, further analyses are legitimated and desirable. PMID:22362332

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

    PubMed

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

    2015-12-01

    Proteomic studies including marine mammals are rare, largely due to the lack of fully sequenced genomes. This has hampered the application of these techniques toward biomarker discovery efforts for monitoring of health and disease in these animals. We conducted a pilot label-free LC-MS/MS study to profile and compare the cerebrospinal fluid from California sea lions with domoic acid toxicosis (DAT) and without DAT. Across 11 samples, a total of 206 proteins were identified (FDR<0.1) using a composite mammalian database. Several peptide identifications were validated using stable isotope labeled peptides. Comparison of spectral counts revealed seven proteins that were elevated in the cerebrospinal fluid from sea lions with DAT: complement C3, complement factor B, dickkopf-3, malate dehydrogenase 1, neuron cell adhesion molecule 1, gelsolin, and neuronal cell adhesion molecule. Immunoblot analysis found reelin to be depressed in the cerebrospinal fluid from California sea lions with DAT. Mice administered domoic acid also had lower hippocampal reelin protein levels suggesting that domoic acid depresses reelin similar to kainic acid. In summary, proteomic analysis of cerebrospinal fluid in marine mammals is a useful tool to characterize the underlying molecular pathology of neurodegenerative disease. All MS data have been deposited in the ProteomeXchange with identifier PXD002105 (http://proteomecentral.proteomexchange.org/dataset/PXD002105). PMID:26364553

  11. Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial meningitis.

    PubMed

    Paradowski, M; Lobos, M; Kuydowicz, J; Krakowiak, M; Kubasiewicz-Ujma, B

    1995-08-01

    We carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment. Convenience of serum sampling constitutes an advantage over traditional BM parameters in CSF. PMID:8521602

  12. High resolution protein electrophoresis of 100 paired canine cerebrospinal fluid and serum.

    PubMed

    Behr, Sébastien; Trumel, Cathy; Cauzinille, Laurent; Palenché, Florence; Braun, Jean-Pierre

    2006-01-01

    This study was performed to investigate the diagnostic relevance of cerebrospinal fluid (CSF) high resolution electrophoresis. The laboratory technique was applied to 100 paired samples of canine CSF and serum, with paired samples tested during the same analytical run, as recommended in human medicine. Ninety four of the dogs had a neurological disease and 6 healthy dogs served as a control group. A strong linear correlation between CSF total protein concentration and the albumin quota (AQ) was found in the control group and in the inflammatory (infectious or noninfectious), neoplastic, and miscellaneous groups: AQ = 0.015 CSF total protein--0.102, r = 0.990. This correlation suggests that an increased CSF total protein concentration can be an indicator of blood brain barrier dysfunction. The highest median AQ value was found in the aseptic suppurative meningitis group, but no statistical differences were found between this and the other groups. The AQ, calculated with this technique, did not provide any additional information. Moreover, although unexpected, the electrophoretic profiles were not characteristic of any particular disease. In conclusion, this study did not confirm high resolution electrophoresis of paired CSF and serum samples to be a valuable ancillary diagnostic tool for canine neurological diseases. PMID:16734104

  13. Analysis of cerebro-spinal fluid protein composition in early developmental stages in chick embryos.

    PubMed

    Gato, A; Martín, P; Alonso, M I; Martín, C; Pulgar, M A; Moro, J A

    2004-04-01

    Foetal cerebro-spinal fluid (CSF) has a very high protein concentration when compared to adult CSF, and in many species five major protein fractions have been described. However, the protein concentration and composition in CSF during early developmental stages remains largely unknown. Our results show that in the earliest stages (18 to 30 H.H.) of chick development there is a progressive increase in CSF protein concentration until foetal values are attained. In addition, by performing electrophoretic separation and high-sensitivity silver staining, we were able to identify a total of 21 different protein fractions in the chick embryo CSF. In accordance with the developmental pattern of their concentration, these can be classified as follows: A: high-concentration fractions which corresponded with the ones described in foetal CSF by other authors; B: low-concentration fractions which remained stable throughout the period studied; C: low-concentration fractions which show changes during this period. The evolution and molecular weight of the latter group suggest the possibility of an important biological role. Our data demonstrate that all the CSF protein fractions are present in embryonic serum; this could mean that the specific transport mechanisms in neuroepithelial cells described in the foetal period evolve in very early stages of development. In conclusion, this paper offers an accurate study of the protein composition of chick embryonic CSF, which will help the understanding of the influences on neuroepithelial stem cells during development and, as a result, the appropriate conditions for the in vitro study of embryonic/foetal nervous tissue cells. PMID:15039986

  14. Amyloid beta protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer's disease.

    PubMed

    Nakamura, T; Shoji, M; Harigaya, Y; Watanabe, M; Hosoda, K; Cheung, T T; Shaffer, L M; Golde, T E; Younkin, L H; Younkin, S G

    1994-12-01

    The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD. PMID:7998778

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

    PubMed

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

    2015-07-01

    Frontotemporal lobar degeneration (FTLD) comprises a spectrum of rare neurodegenerative diseases with an estimated prevalence of 15-22 cases per 100,000 persons including the behavioral variant of frontotemporal dementia (bvFTD), progressive non-fluent aphasia (PNFA), semantic dementia (SD), FTD with motor neuron disease (FTD-MND), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The pathogenesis of the diseases is still unclear and clinical diagnosis of FTLD is hampered by overlapping symptoms within the FTLD subtypes and with other neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Intracellular protein aggregates in the brain are a major hallmark of FTLD and implicate alterations in protein metabolism or function in the disease's pathogenesis. Cerebrospinal fluid (CSF) which surrounds the brain can be used to study changes in neurodegenerative diseases and to identify disease-related mechanisms or neurochemical biomarkers for diagnosis. In the present review, we will give an overview of the current literature on proteomic studies in CSF of FTLD patients. Reports of targeted and unbiased proteomic approaches are included and the results are discussed in regard of their informative value about disease pathology and the suitability to be used as diagnostic biomarkers. Finally, we will give some future perspectives on CSF proteomics and a list of candidate biomarkers which might be interesting for validation in further studies. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. PMID:25526887

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

    PubMed Central

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

    1999-01-01

    The diagnosis of human neurobrucellosis usually relies on the detection of antibodies to Brucella lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) by agglutination tests or enzyme-linked immunosorbent assay (ELISA). Here we describe the detection of immunoglobulin G (IgG) to cytoplasmic proteins (CP) of Brucella spp. by ELISA and Western blotting in seven CSF samples from five patients with neurobrucellosis. While IgG to CP (titers of 200 to 12,800) and IgG to LPS (800 to 6,400) were found in the CSF of these patients, these antibodies were not detected in CSF samples from two patients who had systemic brucellosis without neurological involvement. The latter, however, had serum IgG and IgM to both LPS and CP. No reactivity to these antigens was found in CSF samples from 14 and 20 patients suffering from nonbrucellar meningitis and noninfectious diseases, respectively. These findings suggest that, in addition to its usefulness in the serological diagnosis of human systemic brucellosis, the ELISA with CP antigen can be used for the specific diagnosis of human neurobrucellosis. PMID:10473531

  17. Interference of Cerebrospinal Fluid Total Protein Measurement by Povidone-Iodine Contamination

    PubMed Central

    Gounden, Verena; Sacks, David B; Zhao, Zhen

    2014-01-01

    Background A falsely high cerebrospinal fluid (CSF) total protein (TP) result measured by pyrogallol red (PGR) method was suspected to be caused by preparation of the collection site with povidone-iodine (PVP-iodine) solution. Methods CSF TP was evaluated for interference in samples with different final concentrations of PVP-iodine (up to 0.25% PVP and 0.025% iodine) or iodine alone (up to 0.025% iodine) using three methods: PGR, modified biuret and benzethonium chloride (BZTC). Interference exceeding ±20% of the baseline value is considered clinically significant according the criterion defined by College of American Pathologists. Results There was a positive interference with the PGR method and a negative inference for the BZTC method in CSF samples spiked with PVP-iodine. The PVP-iodine (up to 0.25% PVP and 0.025% iodine) did not cause a clinically significant interference with the modified biuret method. PVP alone without iodine caused a positive interference with the PGR method but did not interfere with the modified biuret or the BZTC method. When the samples were spiked with iodine alone, none of the three methods was affected (change < 20%) by iodine concentration up to 0.025%. Conclusions Contamination of CSF specimens with PVP-iodine can lead to interference with CSF TP measurements using PGR or BZTC methods. PMID:25446880

  18. [Cerebrospinal fluid syndrome in neuroschistosomiasis].

    PubMed

    Livramento, J A; Machado, L R; da Silva, L C; Spina-França, A

    1985-12-01

    A study was made of 220 samples of cerebrospinal fluid (CSF) from patients who suffered from several diseases of the central nervous system. In all samples immunological reactions for syphilis, cysticercosis, toxoplasmosis, Chagas' disease and schistosomiasis were studied comparatively. Immunofluorescent reactions for schistosomiasis were made by indirect antiglobulin technic with two types of antigen: the worm and the liver granuloma of hamster infected by Schistosoma mansoni. Emphasis is given on data concerning to 16 cases in which these reactions were reagent. The importance of routine search in the CSF for schistosomiasis antibodies is discussed. The concept of a 'CSF neuroschistosomiasis syndrome' is discussed as the main aspect of diagnosis "in vivo" of the disease. It is supported by the demonstration of specific antibodies in the CSF. Hypercytosis of lymphomononuclear type associated to the presence of eosinophil cells, protein concentration increase and gamma globulins increase are other characteristics found in the CSF in this syndrome. PMID:3938654

  19. Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.

    PubMed

    Yakushev, Igor; Muller, Matthias J; Buchholz, Hans-Georg; Lang, Ulrike; Rossmann, Heidi; Hampel, Harald; Schreckenberger, Mathias; Fellgiebel, Andreas

    2012-02-01

    Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE > 20 points, n=30) and moderate (MMSE < 21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [κ]=0.34, p=0.016) for t-tau, 68% (κ=0.10, n.s.) for p-tau181, and 68% (κ=0.04, n.s.) for Aβ1-42. No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, κ=0.77, p=0.001) and p-tau181 (88%, κ=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer's dementia, while this is not the case in subjects at an earlier disease stage. PMID:22044023

  20. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients

    PubMed Central

    Wild, Edward J.; Boggio, Roberto; Langbehn, Douglas; Robertson, Nicola; Haider, Salman; Miller, James R.C.; Zetterberg, Henrik; Leavitt, Blair R.; Kuhn, Rainer; Tabrizi, Sarah J.; Macdonald, Douglas; Weiss, Andreas

    2015-01-01

    BACKGROUND: Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington’s disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously. METHODS: We developed an ultrasensitive single-molecule counting (SMC) mHTT immunoassay that was used to quantify mHTT levels in CSF samples from individuals bearing the HD mutation and from control individuals in 2 independent cohorts. RESULTS: This SMC mHTT immunoassay demonstrated high specificity for mHTT, high sensitivity with a femtomolar detection threshold, and a broad dynamic range. Analysis of the CSF samples showed that mHTT was undetectable in CSF from all controls but quantifiable in nearly all mutation carriers. The mHTT concentration in CSF was approximately 3-fold higher in patients with manifest HD than in premanifest mutation carriers. Moreover, mHTT levels increased as the disease progressed and were associated with 5-year onset probability. The mHTT concentration independently predicted cognitive and motor dysfunction. Furthermore, the level of mHTT was associated with the concentrations of tau and neurofilament light chain in the CSF, suggesting a neuronal origin for the detected mHTT. CONCLUSIONS: We have demonstrated that mHTT can be quantified in CSF from HD patients using the described SMC mHTT immunoassay. Moreover, the level of mHTT detected is associated with proximity to disease onset and diminished cognitive and motor function. The ability to quantify CSF mHTT will facilitate the study of HD, and mHTT quantification could potentially serve as a biomarker for the development and testing of experimental mHTT-lowering therapies for HD. TRIAL REGISTRATION: Not applicable. FUNDING: CHDI Foundation Inc.; Medical Research Council (MRC) UK; National Institutes for Health Research (NIHR); Rosetrees

  1. Cerebrospinal fluid culture

    MedlinePlus

    ... is a laboratory test to look for bacteria, fungi, and viruses in the normally clear fluid that ... The laboratory personnel watch to see if bacteria, fungi, or viruses grow in the dish. Growth means ...

  2. Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia

    PubMed Central

    2013-01-01

    Background Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype. Methods We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed. Result NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017). Conclusions The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the

  3. Cerebrospinal fluid otorhinorrhea due to cochlear dysplasias.

    PubMed

    Syal, Rajan; Tyagi, Isha; Goyal, Amit

    2005-07-01

    Cochlear dysplasia associated with defect in stapes footplate can be a cause of cerebrospinal fluid leak. Repair of cerebrospinal fluid leak in these cases is usually done by packing the vestibule with muscle or fascia. This traditional method of repair has 30-60% failure rate. Cerebrospinal fluid leak in four such patients was successfully repaired using multiple layer packing of vestibule, reinforced by pedicle temporalis muscle graft. Intraoperatively continuous lumbar drain was done. Magnetic resonance imaging of inner ear using 3D FSE T2WI and 3D FIESTA sequences was found helpful noninvasive investigation to localize site and route of cerebrospinal fluid leak. PMID:15911019

  4. [Cerebrospinal fluid diagnostics for neuroinfectious diseases].

    PubMed

    Spreer, A; Nau, R

    2015-02-01

    Cerebrospinal fluid analysis is of prime importance to establish an early diagnosis of central nervous system infections. Beside the basic diagnostics containing CSF white cell count, lactate concentration and protein analysis, the targeted search for agents of bacterial, viral or fungal CNS infectious diseases is essential. Decisive methods are bacterial and fungal staining techniques, microbiological culture methods, nucleic acid amplification and antigen detection methods or indirect identification of pathogens by serologic testings including the determination of pathogen-specific intrathecal immunoglobulin synthesis. Besides imparting basic principles of cerebrospinal fluid analysis, this article focuses on special aspects of detection of infectious agents. Well-directed questions and a close communication between clinician and laboratory allow optimal diagnostic analysis for successful confirmation of the diagnosis and for optimal treatment of the patient. PMID:25723775

  5. Protein biomarkers in Parkinson's disease: Focus on cerebrospinal fluid markers and synaptic proteins.

    PubMed

    Halbgebauer, Steffen; Öckl, Patrick; Wirth, Katharina; Steinacker, Petra; Otto, Markus

    2016-06-01

    Despite extensive research, to date, no validated biomarkers for PD have been found. This review seeks to summarize studies approaching the detection of biomarker candidates for PD and introduce promising ones in more detail, with special attention to synaptic proteins. To this end, we performed a PubMed search and included studies using proteomic tools (2-dimensional difference in gel electrophoresis and/or mass spectrometry) for the comparison of samples from PD and control patients. We found 27 studies reporting more than 500 differentially expressed proteins in which a total of 28 were detected in 2 and 17 in 3 or more independent studies, including posttranslationally modified proteins. In addition, of these 500 proteins, 25 were found to be brain specific, and 14 were enriched in synapses. Special attention was given to the applicability of the biomarker regarding sampling procedures, that is, using CSF/serum material for diagnosis. Furthermore, presynaptic proteins involved in vesicle membrane fusion seem to be interesting candidates for future analyses. Nonetheless, even though such promising biomarker candidates for PD exist, validation of these biomarkers in large-scale clinical studies is necessary to evaluate the diagnostic potential. © 2016 International Parkinson and Movement Disorder Society. PMID:27134134

  6. Vitamin D Binding Protein Isoforms and Apolipoprotein E in Cerebrospinal Fluid as Prognostic Biomarkers of Multiple Sclerosis

    PubMed Central

    Lis, Katarzyna; Minari, Nicoletta; Falvo, Sara; Marnetto, Fabiana; Caldano, Marzia; Reviglione, Raffaella; Berchialla, Paola; Capobianco, Marco A.; Malentacchi, Maria; Corpillo, Davide; Bertolotto, Antonio

    2015-01-01

    Background Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a heterogeneous and unpredictable course. To date there are no prognostic biomarkers even if they would be extremely useful for early patient intervention with personalized therapies. In this context, the analysis of inter-individual differences in cerebrospinal fluid (CSF) proteome may lead to the discovery of biological markers that are able to distinguish the various clinical forms at diagnosis. Methods To this aim, a two dimensional electrophoresis (2-DE) study was carried out on individual CSF samples from 24 untreated women who underwent lumbar puncture (LP) for suspected MS. The patients were clinically monitored for 5 years and then classified according to the degree of disease aggressiveness and the disease-modifying therapies prescribed during follow up. Results The hierarchical cluster analysis of 2-DE dataset revealed three protein spots which were identified by means of mass spectrometry as Apolipoprotein E (ApoE) and two isoforms of vitamin D binding protein (DBP). These three protein spots enabled us to subdivide the patients into subgroups correlated with clinical classification (MS aggressive forms identification: 80%). In particular, we observed an opposite trend of values for the two protein spots corresponding to different DBP isoforms suggesting a role of a post-translational modification rather than the total protein content in patient categorization. Conclusions These findings proved to be very interesting and innovative and may be developed as new candidate prognostic biomarkers of MS aggressiveness, if confirmed. PMID:26046356

  7. The Maze of the Cerebrospinal Fluid Discovery

    PubMed Central

    2013-01-01

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

  8. Osmotic demyelination and hypertonic dehydration in a 9-year-old girl: changes in cerebrospinal fluid myelin basic protein.

    PubMed

    Shah, Bobby; Tobias, Joseph D

    2006-01-01

    A 9-year-old girl was admitted for the treatment of hyper-natremic dehydration. Her history was significant for psychogenic polydipsia, hyponatremia, and a renal concentrating defect. She presented with a 2-day history of altered mental status, ataxia, lethargy, fever, nausea, vomiting, and diarrhea. Meningitis was ruled out. Over the course of her illness, slow rehydration was maintained with a gradual decrease (10 mEq per 24 hours) of the serum sodium. Despite this care, she developed quadriparesis, and magnetic resonance imaging performed on day 6 of her illness was consistent with osmotic demyelination (central pontine myelinolysis). To rule out an excessively rapid correction of hypernatremia as the etiology of the problem, a myelin basic protein was measured in the cerebrospinal fluid that had been obtained on hospital day 1. The myelin basic protein was 649.50 ng/mL (normal, 0.07-4.10 ng/mL). The current literature is presented regarding the postulated pathogenesis of central pontine myelinolysis and suggested therapies, previous reports of central pontine myelinolysis in children are reviewed, and the potential role of myelin basic protein in its diagnosis is discussed. PMID:17095502

  9. Cerebrospinal fluid flow in adults.

    PubMed

    Bradley, William G; Haughton, Victor; Mardal, Kent-Andre

    2016-01-01

    This chapter uses magnetic resonance imaging phase-contrast cerebrospinal fluid (CSF) flow measurements to predict which clinical normal-pressure hydrocephalus (NPH) patients will respond to shunting as well as which patients with Chiari I are likely to develop symptoms of syringomyelia. Symptomatic NPH patients with CSF flow (measured as the aqueductal CSF stroke volume) which is shown to be hyperdynamic (defined as twice normal) are quite likely to respond to ventriculoperitoneal shunting. The hyperdynamic CSF flow results from normal systolic brain expansion compressing the enlarged ventricles. When atrophy occurs, there is less brain expansion, decreased aqueductal CSF flow, and less likelihood of responding to shunting. It appears that NPH is a "two-hit" disease, starting as benign external hydrocephalus in infancy, followed by deep white-matter ischemia in late adulthood, which causes increased resistance to CSF outflow through the extracellular space of the brain. Using computational flow dynamics (CFD), CSF flow can be modeled at the foramen magnum and in the upper cervical spine. As in the case of NPH, hyperdynamic CSF flow appears to cause the signs and symptoms in Chiari I and can provide an additional indication for surgical decompression. CFD can also predict CSF pressures over the cardiac cycle. It has been hypothesized that elevated pressure pulses may be a significant etiologic factor in some cases of syringomyelia. PMID:27432684

  10. Proteome analysis of chick embryonic cerebrospinal fluid.

    PubMed

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

    2006-01-01

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

  11. Characterization of individual mouse cerebrospinal fluid proteomes

    SciTech Connect

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

    2014-03-20

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

  12. Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study

    PubMed Central

    Westhoff, Dunja; Witlox, Joost; van Aalst, Corneli; Scholtens, Rikie M.; de Rooij, Sophia E.; van Munster, Barbara C.; de Jonghe, Jos F.M.; Houdijk, Alexander P.J.; Eikelenboom, Piet; van Westerloo, David J.; van de Beek, Diederik; van Gool, Willem A.; Koenderman, Leo

    2015-01-01

    Background A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery. Methods Patients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays. Results In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium. Conclusion Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings. General significance This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling. PMID:26675981

  13. The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog.

    PubMed

    Shafie, Intan N F; McLaughlin, Mark; Burchmore, Richard; Lim, Mary Ann A; Montague, Paul; Johnston, Pamela E J; Penderis, Jacques; Anderson, Thomas J

    2014-05-01

    Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent

  14. Quantification of Plasmodium falciparum Histidine-Rich Protein-2 in Cerebrospinal Spinal Fluid from Cerebral Malaria Patients

    PubMed Central

    Mikita, Kei; Thakur, Kiran; Anstey, Nicholas M.; Piera, Kim A.; Pardo, Carlos A.; Weinberg, J. Brice; Mukemba, Jackson; Florence, Salvatore; Mwaikambo, Esther D.; Granger, Donald L.; Sullivan, David J.

    2014-01-01

    A cerebrospinal fluid (CSF) biomarker for cerebral malaria (CM) has not been validated. We examined the detection, semiquantification, and clinical use of the Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) as a parasite antigen biomarker for CM. The PfHRP-2 was detected in archival CSF samples from CM patients from Tanzania both by a newly developed sensitive and specific immuno-polymerase chain reaction (72 of 73) and by rapid diagnostic tests (62 of 73). The geometric mean PfHRP-2 CSF concentration was 8.76 ng/mL with no differences in those who survived (9.2 ng/mL), those who died (11.1 ng/mL), and those with neurologic sequelae (10.8 ng/mL). All aparasitemic endemic and nonendemic control samples had undetectable CSF PfHRP-2. In a separate group of 11 matched plasma and CSF cerebral malaria patient samples, the ratio of plasma to CSF PfHRP-2 was 175. The CSF PfHRP-2 reflects elevated plasma PfHRP-2 rather than elevated CM-specific CSF ratios, falling short of a validated biomarker. PMID:24980497

  15. Cerebrospinal fluid protein and glucose examinations and tuberculosis:
Will laboratory safety regulations force a change of practice?

    PubMed Central

    Tormey, William P.; O’Hagan, Christopher

    2015-01-01

    Cerebrospinal fluid (CSF) protein and glucose examinations are usually performed in chemical pathology departments on autoanalysers. Tuberculosis (TB) is a group 3 biological agent under Directive 2000/54/EC of the European Parliament but in the biochemistry laboratory, no extra precautions are taken in its analysis in possible TB cases. The issue of laboratory practice and safety in the biochemical analyses of CSF specimens, when tuberculosis infection is in question is addressed in the context of ambiguity in the implementation of current national and international health and safety regulations. Additional protective measures for laboratory staff during the analysis of CSF TB samples should force a change in current laboratory practice and become a regulatory issue under ISO 15189. Annual Mantoux skin test or an interferon-γ release assay for TB should be mandatory for relevant staff. This manuscript addresses the issue of biochemistry laboratory practice and safety in the biochemical analyses of CSF specimens when tuberculosis infection is in question in the context of the ambiguity of statutory health and safety regulations. PMID:26526598

  16. [Diagnosis of spinal diseases by cerebrospinal fluid examination].

    PubMed

    Schmidt, R M

    1979-01-01

    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

  17. Reduced bacterial adhesion to hydrocephalus shunt catheters mediated by cerebrospinal fluid proteins.

    PubMed Central

    Brydon, H L; Bayston, R; Hayward, R; Harkness, W

    1996-01-01

    BACKGROUND--Prosthetic infections are a major problem, requiring complex and lengthy management. The role of blood proteins in the pathogenesis of implant infection has been investigated, but research into the role of CSF protein in shunt infections has not been undertaken, even though a high CSF protein has been assumed to increase the risk of such infections. METHODS--New shunt catheters were exposed to either CSF or individual protein solutions, and the numbers of radiolabelled staphylococci that adhered to them were compared with controls that had been exposed to saline only. RESULTS--A significant reduction in bacteria adhering to the test catheter was found in each instance. Furthermore, the CSF with the highest protein content, from a patient with intraventricular haemorrhage, had the greatest inhibitory effect on bacterial adhesion. The effect of the solutions on the hydrophobicity of the silicone rubber was also investigated. The silicone rubber was more hydrophilic, and bacterial adhesion was less, with solutions containing a higher protein content, and these findings were in keeping with the current theories on the mechanism of bacterial adhesion to polymers. CONCLUSIONS--A high CSF protein content does not predispose to the development of shunt infections. PMID:8648336

  18. Acute effect of protein or carbohydrate breakfasts on human cerebrospinal fluid monoamine precursor and metabolite levels.

    PubMed

    Teff, K L; Young, S N; Marchand, L; Botez, M I

    1989-01-01

    Patients with normal pressure hydrocephalus who had three lumbar punctures during 1 week ingested either water, a protein breakfast, or a carbohydrate breakfast 2.5 h before each of the lumbar punctures. The CSF was analyzed for biogenic amine precursors and metabolites. The protein meal raised CSF tyrosine levels, a finding consistent with animal data, but did not alter those of tryptophan or any of the biogenic amine metabolites. The carbohydrate meal increased CSF 3-methoxy-4-hydroxyphenylethylene glycol, an unexplained finding. The carbohydrate meal did not affect CSF tryptophan, tyrosine, 5-hydroxyindoleacetic acid, or homovanillic acid. Our results support the idea that in humans protein or carbohydrate meals do not alter plasma amino acid levels sufficiently to cause appreciable changes in CNS tryptophan levels or 5-hydroxytryptamine synthesis. PMID:2462018

  19. Proopiomelanocortin, agouti-related protein, and leptin in human cerebrospinal fluid: correlations with body weight and adiposity.

    PubMed

    Page-Wilson, Gabrielle; Meece, Kana; White, Anne; Rosenbaum, Michael; Leibel, Rudolph L; Smiley, Richard; Wardlaw, Sharon L

    2015-09-01

    Leptin and its neuronal targets, which produce proopiomelanocortin (POMC) and agouti-related protein (AgRP), regulate energy balance. This study characterized leptin, POMC, and AgRP in the cerebrospinal fluid (CSF) of 47 healthy human subjects, 23 lean and 24 overweight/obese (OW/OB), as related to BMI, adiposity, plasma leptin, soluble leptin receptor (s-OB-R), and insulin. POMC was measured since the POMC prohormone is the predominant POMC peptide in CSF and correlates with hypothalamic POMC in rodents. Plasma AgRP was similarly characterized. CSF leptin was 83-fold lower than in plasma and correlated strongly with BMI, body fat, and insulin. The relative amount of leptin transported into CSF declined with increasing BMI, ranging from 4.5 to 0.52%, consistent with a saturable transport mechanism. CSF sOB-R was 78-fold lower than in plasma and correlated negatively with plasma and CSF leptin. CSF POMC was higher in lean vs. OW/OB subjects (P < 0.001) and correlated negatively with CSF leptin (r = -0.60, P < 0.001) and with plasma leptin, insulin, BMI, and adiposity. CSF AgRP was not different in lean vs. OW/OB; however, plasma AgRP was higher in lean subjects (P = 0.001) and correlated negatively with BMI, adiposity, leptin, insulin, and HOMA (P < 0.005). Thus, CSF measurements may provide useful biomarkers for brain leptin and POMC activity. The striking negative correlation between CSF leptin and POMC could be secondary to leptin resistance and/or neuronal changes associated with obesity but may also indicate that POMC plays a primary role in regulating body weight and adiposity. The role of plasma AgRP as a neuroendocrine biomarker deserves further study. PMID:26152765

  20. Elevated Cellular Retinoic Acid Binding Protein-I in Cerebrospinal Fluid of Patients with Hemorrhagic Cerebrovascular Diseases : Preliminary Study

    PubMed Central

    Jeon, Jin Pyeong; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Seung-Ki; Oh, Chang Wan

    2015-01-01

    Objective Elevated cellular retinoic acid binding protein-I (CRABP-I) is thought to be related to the abnormal proliferation and migration of smooth muscle cells (SMCs). Accordingly, a higher CRABP-I level could cause disorganized vessel walls by causing immature SMC phenotypes and altering extracellular matrix proteins which could result in vulnerable arterial walls with inadequate responses to hemodynamic stress. We hypothesized that elevated CRABP-I level in the cerebrospinal fluid (CSF) could be related to subarachnoid hemorrhage (SAH). Moreover, we also extended this hypothesis in patients with vascular malformation according to the presence of hemorrhage. Methods We investigated the CSF of 26 patients : SAH, n=7; unruptured intracranial aneurysm (UIA), n=7; arteriovenous malformation (AVM), n=4; cavernous malformation (CM), n=3; control group, n=5. The optical density of CRABP-I was confirmed by Western blotting and presented as mean±standard error of the measurement. Results CRABP-I in SAH (0.33±0.09) was significantly higher than that in the UIA (0.12±0.01, p=0.033) or control group (0.10±0.01, p=0.012). Hemorrhage presenting AVM (mean 0.45, ranged 0.30-0.59) had a higher CRABP-I level than that in AVM without hemorrhage presentation (mean 0.16, ranged 0.14-0.17). The CRABP-I intensity in CM with hemorrhage was 0.21 and 0.31, and for CM without hemorrhage 0.14. Overall, the hemorrhage presenting group (n=11, 0.34±0.06) showed a significantly higher CRABP-I intensity than that of the non-hemorrhage presenting group (n=10, 0.13±0.01, p=0.001). Conclusion The results suggest that elevated CRABP-I in the CSF could be related with aneurysm rupture. Additionally, a higher CRABP-I level seems to be associated with hemorrhage development in vascular malformation. PMID:25733988

  1. Endonasal Endoscopic Closure of Cerebrospinal Fluid Rhinorrhea

    PubMed Central

    Schmerber, S.; Righini, Ch.; Lavielle, J.-P.; Passagia, J.-G.; Reyt, E.

    2001-01-01

    The authors review their experience with endoscopic repair of skull base defects associated with cerebrospinal fluid (CSF) rhinorrhea involving the paranasal sinuses. A total of 22 patients was treated endoscopically between 1992 and 1998. The repair method consisted of closure of the CSF fistula with a free autologous abdominal fat graft and fibrin glue, supported with a sheet of silastic. The primary closure rate was 82% (18/22), and the overall closure rate was 95.5% (21/22) without recurrence or complications within an average follow-up of 5 years (14-83 months). A single patient still complains of cerebrospinal rhinorrhea, although this was never proved by any clinical, endoscopic, or biological (β2-transferrin) examination. The repair of ethmoidal-sphenoidal cerebrospinal fluid fistulae by endonasal endoscopic surgery is an excellent technique, both safe and effective. Fat is a material of choice, as it is tight and resists infection well. The technique and indications for endoscopic management of cerebrospinal fluid leaks are discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:17167603

  2. [BLOOD AND CEREBROSPINAL FLUID PURINES IN PREGNANT].

    PubMed

    Oreshnikov, E V; Oreshnikov, S F

    2015-01-01

    The research includes 88 pregnant women, that had their purine basis and malondialdehyde in water thermocoagulate extract of venous blood and cerebrospinal fluid examined (along with common standards clinical-laboratory tests) before the spinal anesthesia for the caesarian section was provided It was detected that preeclampsy and HELLP-syndine feature the increased adenine guanine hypoxantine and uric acid levels in cerebrospinal fluid, as well as increased concentrations of blood malondyaldehyde (higher than upper normal level), accompany with the increased hemotaencephalic barrier permeability for adenine, guanine and hypoxantine. It's demonstrated that level of guanine in blood serum can be used as a prognostic factor of spinal anesthesia quality in obstetrics. It is supposed to examine purine levels in pregnant women not only in blood but also in cere brospinal fluid. PMID:26596029

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

    PubMed

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

    2014-03-01

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

  4. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

    PubMed Central

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

    2014-01-01

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

  5. Spontaneous cerebrospinal fluid leak at the clivus

    PubMed Central

    Składzien, Jacek; Betlej, Marek; Chrzan, Robert; Mika, Joanna

    2015-01-01

    We present a case report of a 60-year-old woman with a spontaneous cerebrospinal fluid leak at the clivus, obesity and no history of trauma. Follow-up imaging scans confirmed enlargement of the defect within the posterior clival framework to the size of 16 × 9 × 4 mm with a suspected meningocerebral hernia. The surgeons used the “two nostrils – four hands” endoscopic operating technique. The patient reported a history of cerebrospinal fluid leaks lasting for 3 years, with increasingly shorter leak-free periods and an increasing incidence of inflammatory complications. The patient recovered without complications, and she was discharged 14 days after the surgery. Good local outcome and improved patient condition were achieved postoperatively. PMID:26865899

  6. Malignancy markers in the cerebrospinal fluid.

    PubMed

    Koskiniemi, M

    1988-10-01

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

  7. Cerebrospinal fluid analysis after unprovoked first seizure

    PubMed Central

    Zisimopoulou, Vaso; Mamali, Margarita; Katsavos, Serafeim; Siatouni, Anna; Tavernarakis, Antonios; Gatzonis, Stylianos

    2016-01-01

    Summary The aim of this study was to determine cerebrospinal fluid (CSF) characteristics after an unprovoked first seizure (UFS). We reviewed the medical records of 71 patients with UFS who underwent lumbar puncture, and examined the CSF parameters. Each CSF parameter was evaluated separately for potential correlations with the other study variables. We observed an overall frequency of CSF abnormalities of 35.2%. CSF protein was the most common abnormal parameter (31%) and showed significant positive correlations with male gender (p=0.037) and older age (p=0.007). Only seven patients (9.9%) had an abnormal cell count (5–40 cells/μl). Higher CSF cell counts were found to predict a longer hospitalization period (p=0.005). No relationship with abnormal EEG findings could be established (p=0.169). This study is one of the few to evaluate postictal CSF parameters in a clinical setting, and to our knowledge the first to investigate these parameters specifically in the emergency department. The development of a rapid, easy-to-use test that does not require extensive laboratory equipment to differentiate UFS from other conditions could be of great value in everyday clinical practice. PMID:27358223

  8. All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development.

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2008-06-11

    Embryonic cerebrospinal fluid (E-CSF) is involved in the regulation of survival, proliferation and neurogenesis of neuroectodermal progenitor cells, as well as in the control of mesencephalic gene expression in collaboration with the isthmic organizer. Recently, we showed the presence of retinol-binding protein (RBP) within the E-CSF proteome. RBP is an all-trans retinol carrier, a molecule that can be metabolized into retinoic acid, a morphogen involved in central nervous system (CNS) morphogenesis and patterning. Here we demonstrate the presence of all-trans retinol within the E-CSF and analyse the dynamics of RBP and all-trans retinol within this fluid, as well as the expression of retinoic acid-synthesizing enzymes during early CNS development. Our results suggest a relationship between the dynamics of these molecules and the early events of CNS patterning. PMID:18520998

  9. Cerebrospinal fluid pressure and the eye.

    PubMed

    Morgan, William H; Balaratnasingam, Chandrakumar; Lind, Christopher R P; Colley, Steve; Kang, Min H; House, Philip H; Yu, Dao-Yi

    2016-01-01

    Cerebrospinal fluid pressure (CSFP) interacts with intraocular pressure (IOP) and blood pressure to exert a major influence upon the eye, particularly the optic nerve head region. There is increased interest regarding the influence of CSFP upon disorders affecting this region, in particular glaucoma and idiopathic intracranial hypertension. Additionally, a high proportion of astronauts develop features similar to idiopathic intracranial hypertension that persist for years after returning to Earth. The factors that affect the CSFP influence upon the optic nerve and globe are likely to influence the outcome of various ophthalmic disorders. PMID:25877896

  10. Extracranial repair of cerebrospinal fluid otorhinorrhea

    SciTech Connect

    Persky, M.S.; Rothstein, S.G.; Breda, S.D.; Cohen, N.L.; Cooper, P.; Ransohoff, J. )

    1991-02-01

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

  11. Cerebrospinal fluid stasis and its clinical significance.

    PubMed

    Whedon, James M; Glassey, Donald

    2009-01-01

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

  12. A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients

    PubMed Central

    Freyhult, Eva; Bodolea, Constantin; Ekegren, Titti; Larsson, Anders; Gustafsson, Mats G.; Katila, Lenka; Bergquist, Jonas; Gordh, Torsten; Landegren, Ulf; Kamali-Moghaddam, Masood

    2016-01-01

    The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest. PMID:26914813

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

    PubMed Central

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

    2009-01-01

    The HIV-1-associated neurocognitive disorder occurs in approximately one-third of infected individuals. It has persisted in the current era of anti-retroviral therapy, and its study is complicated by the lack of biomarkers for this condition. Since the cerebrospinal fluid is the most proximal biofluid to the site of pathology, we studied the cerebrospinal fluid in a nonhuman primate model for HIV-1-associated neurocognitive disorder. Here we present a simple and efficient liquid chromatography coupled mass spectrometry based proteomics approach that utilizes small amounts of cerebrospinal fluid. First, we demonstrate the validity of the methodology using human cerebrospinal fluid. Next, using the simian immunodeficiency virus infected monkey model, we show its efficacy in identifying proteins such as alpha-1-antitrypsin, complement C3, hemopexin, IgM heavy chain and plasminogen, whose increased expression is linked to disease. Finally, we find that the increase in cerebrospinal fluid proteins is linked to increased expression of their genes in the brain parenchyma, revealing that the cerebrospinal fluid alterations identified reflect changes in the brain itself and not merely leakage of the blood-brain or blood- cerebrospinal fluid barriers. This study reveals new central nervous system alterations in lentivirus-induced neurological disease, and this technique can be applied to other systems in which limited amounts of biofluids can be obtained. PMID:19281240

  14. Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease

    PubMed Central

    Khoonsari, Payam Emami; Häggmark, Anna; Lönnberg, Maria; Mikus, Maria; Kilander, Lena; Lannfelt, Lars; Bergquist, Jonas; Ingelsson, Martin; Nilsson, Peter

    2016-01-01

    Alzheimer’s disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer’s disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer’s disease patients and non-demented controls to identify potential biomarkers for Alzheimer’s disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer’s disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer’s disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system. PMID:26950848

  15. Hourly analysis of cerebrospinal fluid glucose shows large diurnal fluctuations.

    PubMed

    Verbeek, Marcel M; Leen, Wilhelmina G; Willemsen, Michèl A; Slats, Diane; Claassen, Jurgen A

    2016-05-01

    Cerebrospinal fluid analysis is important in the diagnostics of many neurological disorders. Since the influence of food intake on the cerebrospinal fluid glucose concentration and the cerebrospinal fluid/plasma glucose ratio is largely unknown, we studied fluctuations in these parameters in healthy adult volunteers during a period of 36 h. Our observations show large physiological fluctuations of cerebrospinal fluid glucose and the cerebrospinal fluid/plasma glucose ratio, and their relation to food intake. These findings provide novel insights into the physiology of cerebral processes dependent on glucose levels such as energy formation (e.g. glycolysis), enzymatic reactions (e.g. glycosylation), and non-enzymatic reactions (e.g. advanced endproduct glycation). PMID:26945018

  16. A new look at cerebrospinal fluid circulation

    PubMed Central

    2014-01-01

    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. PMID:24817998

  17. Imhotep and the Discovery of Cerebrospinal Fluid

    PubMed Central

    Blomstedt, Patric

    2014-01-01

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

  18. Imhotep and the discovery of cerebrospinal fluid.

    PubMed

    Blomstedt, Patric

    2014-01-01

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

  19. Amyloid-β Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease

    PubMed Central

    Barrera-Ocampo, Alvaro; Arlt, Sönke; Matschke, Jakob; Hartmann, Ursula; Puig, Berta; Ferrer, Isidre; Zürbig, Petra; Glatzel, Markus; Jahn, Holger

    2016-01-01

    The mechanisms leading to amyloid-β (Aβ) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with Aβ plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant Aβ precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced Aβ40 and Aβ42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor Aβ accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of Aβ species. PMID:27486134

  20. Amyloid-β Peptides and Tau Protein as Biomarkers in Cerebrospinal and Interstitial Fluid Following Traumatic Brain Injury: A Review of Experimental and Clinical Studies

    PubMed Central

    Tsitsopoulos, Parmenion P.; Marklund, Niklas

    2013-01-01

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

  1. Cerebrospinal Fluid Leakage after Thoracic Decompression

    PubMed Central

    Hu, Pan-Pan; Liu, Xiao-Guang; Yu, Miao

    2016-01-01

    Objective: The objective of this study is to review cerebrospinal fluid leakage (CSFL) after thoracic decompression and describe its regular and special features. Data Sources: Literature cited in this review was retrieved from PubMed and Medline and was primarily published during the last 10 years. “Cerebrospinal fluid”, “leakage”, “dural tears”, and “thoracic decompression” were the indexed terms. Relevant citations in the retrieved articles were also screened to include more data. Study Selection: All retrieved literature was scrutinized, and four categories were recorded: incidence and risk factors, complications, treatment modalities, and prognosis. Results: CSFL is much more frequent after thoracic decompression than after cervical and lumbar spinal surgeries. Its occurrence is related to many clinical factors, especially the presence of ossified ligaments and the adhesion of the dural sac. While its impact on the late neurological recovery is currently controversial, CSFL increases the risk of other perioperative complications, such as low intracranial pressure symptoms, infection, and vascular events. The combined use of primary repairs during the operation and conservative treatment postoperatively is generally effective for most CSFL cases, whereas lumbar drains and reoperations should be implemented as rescue options for refractory cases only. Conclusions: CSFL after thoracic decompression has not been specifically investigated, so the present study provides a systematic and comprehensive review of the issue. CSFL is a multi-factor-related complication, and pathological factors play a decisive role. The importance of CSFL is in its impact on the increased risk of other complications during the postoperative period. Methods to prevent these complications are in need. In addition, though the required treatment resources are not special for CSFL after thoracic decompression, most CSFL cases are conservatively curable, and surgeons should be

  2. More than cell dust: microparticles isolated from cerebrospinal fluid of brain injured patients are messengers carrying mRNAs, miRNAs, and proteins.

    PubMed

    Patz, Silke; Trattnig, Christa; Grünbacher, Gerda; Ebner, Birgit; Gülly, Christian; Novak, Alexandra; Rinner, Beate; Leitinger, Gerd; Absenger, Markus; Tomescu, Oana A; Thallinger, Gerhard G; Fasching, Ulrike; Wissa, Sonja; Archelos-Garcia, Juan; Schäfer, Ute

    2013-07-15

    Microparticles are cell-derived, membrane-sheathed structures that are believed to shuttle proteins, mRNA, and miRNA to specific local or remote target cells. To date best described in blood, we now show that cerebrospinal fluid (CSF) contains similar structures that can deliver RNAs and proteins to target cells. These are, in particular, molecules associated with neuronal RNA granules and miRNAs known to regulate neuronal processes. Small RNA molecules constituted 50% of the shuttled ribonucleic acid. Using microarray analysis, we identified 81 mature miRNA molecules in CSF microparticles. Microparticles from brain injured patients were more abundant than in non-injured subjects and contained distinct genetic information suggesting that they play a role in the adaptive response to injury. Notably, miR-9 and miR-451 were differentially packed into CSF microparticles derived from patients versus non-injured subjects. We confirmed the transfer of genetic material from CSF microparticles to adult neuronal stem cells in vitro and a subsequent microRNA-specific repression of distinct genes. This first indication of a regulated transport of functional genetic material in human CSF may facilitate the diagnosis and analysis of cerebral modulation in an otherwise inaccessible organ. PMID:23360174

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

    PubMed Central

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

    1996-01-01

    To determine the prevalence of cerebrospinal fluid abnormalities in Southeast Asian refugees with reactive serologic tests for syphilis, we evaluated 65 patients, 36 prospectively and 29 retrospectively, in a primary care clinic. Information was collected on history of treponemal infections, neurologic symptoms and signs, and total protein concentration, leukocyte count, and the VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all patients for whom data were available. Abnormal neurologic signs were found or noted in medical records in 15 (42%) prospectively evaluated patients and 9 (64%) of 14 retrospectively evaluated patients for whom data were available. No patient had evidence of congenital or non-neurologic sequelae such as cutaneous or cardiovascular manifestations of syphilis. No patient had a positive cerebrospinal fluid VDRL test, 1 had more than 5 x 10(6) leukocytes per liter (5 leukocytes per mm3), and 6 (9%) had elevated total protein levels in the cerebrospinal fluid. Previous therapy for syphilis was not associated with lower serum VDRL reactions, neurologic symptoms and signs, or cerebrospinal fluid findings. In the absence of other indications, routine examination of the cerebrospinal fluid in seropositive Southeast Asian refugees who have nonspecific neurologic symptoms has a low yield, perhaps because of the high prevalence of yaws in this population, and may not be warranted. PMID:8993199

  4. Tegmental defects and cerebrospinal fluid otorrhea.

    PubMed

    Valtonen, H; Geyer, C; Tarlov, E; Heilman, C; Poe, D

    2001-01-01

    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 beta(2)-transferrin was positive in 2/4, equivocal in 1/4 and false negative in 1/4. Computerized tomography (CT) revealed nonspecific tegmental defects in all 5 patients. Magnetic resonance imaging (MRI) demonstrated meningoencephalocele in 3/5 and dural irregularity in 1/5. Tegmental defects were confirmed at surgery in all cases, demonstrating meningocele or arachnoid granulations in 2/5 and encephalocele in 2/5 patients. We recommend a combination of beta(2)-transferrin analysis to verify CSF, high resolution CT (axial and coronal planes) to diagnose tegmental defects, and MRI (multiplanar) to evaluate the type of herniation. A combination mastoid and middle fossa approach for definitive repair is suggested. PMID:11174062

  5. Cerebrospinal fluid monoamine metabolites and suicide.

    PubMed

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

    2009-01-01

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

  6. Cerebrospinal Fluid Flow Studies and Recent Advancements.

    PubMed

    Kelly, Erin J; Yamada, Shinya

    2016-04-01

    This article provides an overview of magnetic resonance imaging (MRI) techniques used to assess cerebrospinal fluid (CSF) movement in the central nervous system (CNS), including Phase-Contrast (PC), Time-Spatial Labeling Inversion Pulse, and simultaneous multi slice echo planar phase contrast imaging. These techniques have been used to assess CSF movement in the CNS under normal and pathophysiological situations. PC can quantitatively measure stroke volume in selected regions, particularly the aqueduct of Sylvius, as synchronized to the heartbeat. The PC is frequently used to investigate those patients with suspected normal pressure hydrocephalus and a Chiari I malformation. Time-Spatial Labeling Inversion Pulse, with high signal-to-noise ratio, captures motion of CSF anywhere in the CNS over a time period of up to 5 seconds. Variations of PC-MRI improved temporal resolution and included contributions from respiration. With non-invasive imaging such as these, more can be understood about CSF dynamics, especially with respect to the relative effects of cardiac and respiratory changes on CSF movement. PMID:27063659

  7. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    PubMed

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir. PMID:25860317

  8. Characterization and stability of transthyretin isoforms in cerebrospinal fluid examined by immunoprecipitation and high-resolution mass spectrometry of intact protein.

    PubMed

    Poulsen, Keld; Bahl, Justyna M C; Tanassi, Julia T; Simonsen, Anja H; Heegaard, Niels H H

    2012-02-01

    Post-translational modifications (PTMs) contribute significantly to the complexity of proteins. PTMs may vary in certain patterns according to diseases and microenviroments making them potential markers for pathological processes. Human transthyretin (TTR) is a transporter of thyroxine and retinol in blood and cerebrospinal fluid (CSF). A single free cysteine thiol group in TTR possesses the ability to form mixed disulfides potentially related to diseases such as TTR amyloidosis and Alzheimer's disease (AD). Additionally, TTR-Cys10 S-thiolations might mirror the oxidative stress and redox balance of CSF. Here we describe a quick and gentle method for immunoprecipitating (IP) TTR from CSF with minimal introduction of sample-handling artifacts. A high-resolution mass spectrometer (LTQ-Orbitrap XL) was used in a simple setup with direct infusion that generates data suitable for confident assignment of TTR isoforms and validation of the protocol. Moreover, we demonstrate how simple storage of CSF at 4°C induces major oxidative modifications of TTR. Using the optimized method, we show data from a limited number of mild cognitive impairment (MCI) and AD patients. The protocol controls and minimizes the introduction of sample-handling artifacts during purification of TTR isoforms for high-resolution MS analysis. PMID:22286025

  9. Presence of an autoantibody against a Golgi cisternal membrane protein in the serum and cerebrospinal fluid from a patient with idiopathic late onset cerebellar ataxia.

    PubMed

    Gaspar, M L; Marcos, M A; Gutierrez, C; Martín, M J; Bonifacino, J S; Sandoval, I V

    1988-03-01

    Tissue and cultured cells of different species and embryological origins incubated with serum (diluted up to 10,000-fold) or cerebrospinal fluid (CSF) (6-fold dilution) from a 48-year-old female patient with idiopathic late-onset cerebellar ataxia, exhibited a bright specific perinuclear staining when studied by indirect immunofluorescence microscopy. The pattern of the staining was that characteristic of the Golgi apparatus, consisting of a crescent-shaped juxtanuclear reticulum located in the vicinity of the microtubule organizing center. Changes in location and organization of the organelle stained by the patient's serum during mitosis or after incubation of the cells with Colcemid, taxol or monensin, resulted in a disruption of the reticulum that followed the expected patterns for Golgi apparatus. The staining was specifically absorbed with Golgi cisternae-enriched membrane fractions. Finally, dot-immunoblotting studies of membrane and soluble fractions of Golgi cisternae and vesicles showed that the anti-Golgi antibody (AGA) reacted with the cytoplasmic domain of an integral membrane protein contained in the Golgi cisternae. The presence of this unusual autoantibody in an idiopathic late-onset cerebellar ataxia-bearing patient can afford some insights into the pathogenesis of these neurological diseases. PMID:3339121

  10. Cerebrospinal fluid apolipoprotein E and phospholipid transfer protein activity are reduced in multiple sclerosis; relationships with the brain MRI and CSF lipid variables

    PubMed Central

    Vuletic, Simona; Kennedy, Hal; Albers, John J.; Killestein, Joep; Vrenken, Hugo; Lütjohann, Dieter; Teunissen, Charlotte E.

    2014-01-01

    Apolipoprotein E (apoE), phospholipid transfer protein (PLTP) activity, lipids, total tau and beta amyloid 1-42 (Aβ42) were measured in cerebrospinal fluid (CSF) from controls (n=38) and multiple sclerosis (MS) patients (n=91). ApoE and PLTP activity were significantly reduced in MS compared to non-inflammatory disease controls (NINDC; p<0.05). In NINDC and MS, apoE correlated with PLTP activity (rs=0.399 and 0.591, respectively), Aβ42 (rs= 0.609 and 0.483, respectively), and total tau (rs=0.748 and 0.380, respectively; all p<0.05). CSF apoE and PLTP significantly contributed to the variance of the normalized brain volume (NBV) and T2 lesion volume in MS (p<0.001 and p<0.05, respectively). ApoE correlated with CSF cholesterol and 24-hydroxycholesterol in all groups; PLTP activity correlated with CSF cholesterol in controls (p<0.05). PMID:24955324

  11. Endoscopic management of cerebrospinal fluid rhinorrhea

    PubMed Central

    Yadav, Yad Ram; Parihar, Vijay; Janakiram, Narayanan; Pande, Sonjay; Bajaj, Jitin; Namdev, Hemant

    2016-01-01

    Cerebrospinal fluid (CSF) rhinorrhea occurs due to communication between the intracranial subarachnoid space and the sinonasal mucosa. It could be due to trauma, raised intracranial pressure (ICP), tumors, erosive diseases, and congenital skull defects. Some leaks could be spontaneous without any specific etiology. The potential leak sites include the cribriform plate, ethmoid, sphenoid, and frontal sinus. Glucose estimation, although non-specific, is the most popular and readily available method of diagnosis. Glucose concentration of > 30 mg/dl without any blood contamination strongly suggests presence and the absence of glucose rules out CSF in the fluid. Beta-2 transferrin test confirms the diagnosis. High-resolution computed tomography and magnetic resonance cisternography are complementary to each other and are the investigation of choice. Surgical intervention is indicated, when conservative management fails to prevent risk of meningitis. Endoscopic closure has revolutionized the management of CSF rhinorrhea due to its less morbidity and better closure rate. It is usually best suited for small defects in cribriform plate, sphenoid, and ethmoid sinus. Large defects can be repaired when sufficient experience is acquired. Most frontal sinus leaks, although difficult, can be successfully closed by modified Lothrop procedure. Factors associated with increased recurrences are middle age, obese female, raised ICP, diabetes mellitus, lateral sphenoid leaks, superior and lateral extension in frontal sinus, multiple leaks, and extensive skull base defects. Appropriate treatment for raised ICP, in addition to proper repair, should be done to prevent recurrence. Long follow-up is required before leveling successful repair as recurrences may occur very late. PMID:27366243

  12. Endoscopic management of cerebrospinal fluid rhinorrhea.

    PubMed

    Yadav, Yad Ram; Parihar, Vijay; Janakiram, Narayanan; Pande, Sonjay; Bajaj, Jitin; Namdev, Hemant

    2016-01-01

    Cerebrospinal fluid (CSF) rhinorrhea occurs due to communication between the intracranial subarachnoid space and the sinonasal mucosa. It could be due to trauma, raised intracranial pressure (ICP), tumors, erosive diseases, and congenital skull defects. Some leaks could be spontaneous without any specific etiology. The potential leak sites include the cribriform plate, ethmoid, sphenoid, and frontal sinus. Glucose estimation, although non-specific, is the most popular and readily available method of diagnosis. Glucose concentration of > 30 mg/dl without any blood contamination strongly suggests presence and the absence of glucose rules out CSF in the fluid. Beta-2 transferrin test confirms the diagnosis. High-resolution computed tomography and magnetic resonance cisternography are complementary to each other and are the investigation of choice. Surgical intervention is indicated, when conservative management fails to prevent risk of meningitis. Endoscopic closure has revolutionized the management of CSF rhinorrhea due to its less morbidity and better closure rate. It is usually best suited for small defects in cribriform plate, sphenoid, and ethmoid sinus. Large defects can be repaired when sufficient experience is acquired. Most frontal sinus leaks, although difficult, can be successfully closed by modified Lothrop procedure. Factors associated with increased recurrences are middle age, obese female, raised ICP, diabetes mellitus, lateral sphenoid leaks, superior and lateral extension in frontal sinus, multiple leaks, and extensive skull base defects. Appropriate treatment for raised ICP, in addition to proper repair, should be done to prevent recurrence. Long follow-up is required before leveling successful repair as recurrences may occur very late. PMID:27366243

  13. Cerebrospinal fluid proteome of patients with acute Lyme disease

    PubMed Central

    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

    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

  14. Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress.

    PubMed

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

  15. Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress

    PubMed Central

    Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.; LeWitt, Peter A.

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms (“proteostasis”) are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = –0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = –0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: –0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

  16. Multiple isoforms of the tumor protein p73 are expressed in the adult human telencephalon and choroid plexus and present in the cerebrospinal fluid.

    PubMed

    Cabrera-Socorro, Alfredo; Pueyo Morlans, Mercedes; Suarez Sola, Maria Luisa; Gonzalez Delgado, Francisco J; Castañeyra-Perdomo, Agustin; Marin, Maria C; Meyer, Gundela

    2006-04-01

    p73, a homolog of the p53 tumor suppressor, codes for full-length transactivating (TA) and N-terminally truncated (DeltaN) isoforms, with pro- and anti-apoptotic activities, respectively. We examined the expression of the main p73 isoforms in adult human and mouse telencephalon and choroid plexus by immunohistochemistry on paraffin sections, and immunoblotting (IB) of tissue extracts and cerebrospinal fluid (CSF), using antibodies against different protein domains. Cortical neurons expressed TAp73 predominantly in the cytoplasm and DeltaNp73 mainly in the nucleus, with partial overlap in the cytoplasm. Highest expression was found in the hippocampus. IB showed an array of TAp73 variants in adult human cortex and hippocampus. IB of human choroid plexus and CSF using TAp73-specific antibodies revealed the presence of a approximately 90-kDa protein whose molecular weight was reduced after N-deglycosylation, suggesting that glycosylated TAp73 is exported into the CSF. In the mouse, high expression of TAp73 was also detected in the subcommissural organ (SCO), an ependymal gland absent in adult humans. TAp73 colocalized with anti-fibra-Reissner-antibody (AFRU), which is a marker of Reissner's fiber, the secreted SCO product. p73-deficient mice had generalized cortical hypoplasia and hydrocephalus; in addition, we observed a dramatic size reduction of the choroid plexus. However, the SCOs were apparently unaltered and continued to secrete Reissner's fiber. Our findings point to complex and widespread p73 activities in the maintenance of adult cortical neurons and in brain homeostasis. TAp73 in the CSF may play important roles in the maintenance of the adult ventricular wall as well as in the development of the proliferating neuroepithelium. PMID:16630058

  17. Microscale depletion of high abundance proteins in human biofluids using IgY14 immunoaffinity resin: analysis of human plasma and cerebrospinal fluid

    PubMed Central

    Hyung, Seok-Won; Piehowski, Paul D.; Moore, Ronald J.; Orton, Daniel J.; Schepmoes, Athena A.; Clauss, Therese R.; Chu, Rosalie K.; Fillmore, Thomas L.; Brewer, Heather; Liu, Tao; Zhao, Rui; Smith, Richard D.

    2014-01-01

    Removal of highly abundant proteins in plasma is often carried out using immunoaffinity depletion to extend the dynamic range of measurements to lower abundance species. While commercial depletion columns are available for this purpose, they generally are not applicable to limited sample quantities (<20 μL) due to low yields stemming from losses caused by nonspecific binding to the column matrix and concentration of large eluent volumes. Additionally, the cost of the depletion media can be prohibitive for larger-scale studies. Modern LC-MS instrumentation provides the sensitivity necessary to scale-down depletion methods with minimal sacrifice to proteome coverage, which makes smaller volume depletion columns desirable for maximizing sample recovery when samples are limited, as well as for reducing the expense of large-scale studies. We characterized the performance of a 346 μL column volume microscale depletion system, using four different flow rates to determine the most effective depletion conditions for ~6-μL injections of human plasma proteins and then evaluated depletion reproducibility at the optimum flow rate condition. Depletion of plasma using a commercial 10-mL depletion column served as the control. Results showed depletion efficiency of the microscale column increased as flow rate decreased, and that our microdepletion was reproducible. In an initial application, a 600-μL sample of human cerebrospinal fluid (CSF) pooled from multiple sclerosis patients was depleted and then analyzed using reversed phase liquid chromatography-mass spectrometry to demonstrate the utility of the system for this important biofluid where sample quantities are more commonly limited. PMID:25192788

  18. Huntington's disease cerebrospinal fluid seeds aggregation of mutant huntingtin

    PubMed Central

    Tan, Z; Dai, W; van Erp, T G M; Overman, J; Demuro, A; Digman, M A; Hatami, A; Albay, R; Sontag, E M; Potkin, K T; Ling, S; Macciardi, F; Bunney, W E; Long, J D; Paulsen, J S; Ringman, J M; Parker, I; Glabe, C; Thompson, L M; Chiu, W; Potkin, S G

    2015-01-01

    Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. This seeding assay distinguishes HD subjects from healthy and non-HD dementia controls without overlap (blinded samples). Ultimately, this seeding property in HD patient CSF may form the basis of a molecular biomarker assay to monitor HD and evaluate therapies that target mHTT. PMID:26100538

  19. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.

    PubMed

    Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj

    2015-11-01

    Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline

  20. The 1H NMR Profile of Healthy Dog Cerebrospinal Fluid

    PubMed Central

    Musteata, Mihai; Nicolescu, Alina; Solcan, Gheorghe; Deleanu, Calin

    2013-01-01

    The availability of data for reference values in cerebrospinal fluid for healthy humans is limited due to obvious practical and ethical issues. The variability of reported values for metabolites in human cerebrospinal fluid is quite large. Dogs present great similarities with humans, including in cases of central nervous system pathologies. The paper presents the first study on healthy dog cerebrospinal fluid metabolomic profile using 1H NMR spectroscopy. A number of 13 metabolites have been identified and quantified from cerebrospinal fluid collected from a group of 10 mix breed healthy dogs. The biological variability as resulting from the relative standard deviation of the physiological concentrations of the identified metabolites had a mean of 18.20% (range between 9.3% and 44.8%). The reported concentrations for metabolites may be used as normal reference values. The homogeneity of the obtained results and the low biologic variability show that the 1H NMR analysis of the dog’s cerebrospinal fluid is reliable in designing and interpreting clinical and therapeutic trials in dogs with central nervous system pathologies. PMID:24376499

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

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

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

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

    PubMed

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

    2015-09-01

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

  3. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

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

    2012-10-05

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

  4. Embryonic blood-cerebrospinal fluid barrier formation and function

    PubMed Central

    Bueno, David; Parvas, Maryam; Hermelo, Ismaïl; Garcia-Fernàndez, Jordi

    2014-01-01

    During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB) systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF. PMID:25389383

  5. Differential proteomics analysis of mononuclear cells in cerebrospinal fluid of Parkinson’s disease

    PubMed Central

    Xing, Lifei; Wang, Dongtao; Wang, Lihong; Lan, Wenjie; Pan, Suyue

    2015-01-01

    Parkinson’s disease (PD) is one common neurodegenerative disease featured with degeneration of dopaminergic neurons in substantia nigra. Multiple factors participate in the pathogenesis and progression of PD. In this study, we investigated the proteomics profiles of mononuclear cells in cerebrospinal fluids from both PD patients and normal people, in order to explore the correlation between disease factors and PD. Cerebrospinal fluid samples were collected from both PD and normal people and were separated for mononuclear cells in vitro. Proteins were then extracted and separated by 2-dimensional gel electrophoresis. Proteins with differential expressions were identified by comparison to standard proteome expression profile map, followed by software and database analysis. In PD patients, there were 8 proteins with consistent expression profile and 16 proteins with differential expressions. Those differential proteins identified include cytoskeleton proteins (actin, myosin), signal transduction proteins (adenosine cyclase binding protein 1, calcium binding protein, talin) and anti-oxidation factor (thioredoxin peroxide reductase). PD patients had differential protein expressional profiles in the mononuclear cells of cerebrospinal fluids compared to normal people, suggesting the potential involvement of cytoskeleton and signal transduction proteins in apoptosis of neuronal apoptosis and PD pathogenesis. PMID:26823915

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Travis, John

    1999-01-01

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

  9. A new look at cerebrospinal fluid movement

    PubMed Central

    2014-01-01

    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. PMID:25089184

  10. Endostatin level in cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Salza, Romain; Oudart, Jean-Baptiste; Ramont, Laurent; Maquart, François-Xavier; Bakchine, Serge; Thoannès, Henri; Ricard-Blum, Sylvie

    2015-01-01

    The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-β1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-β1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD. PMID:25408220

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

    PubMed

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

    2015-08-01

    To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown. PMID:26339679

  12. Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

    PubMed Central

    Mukaetova-Ladinska, Elizabeta B.; Monteith, Rachael; Perry, Elaine K.

    2010-01-01

    More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (>90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (α-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: α-synuclein reduction in early DLB, a correlation between CSF α-synuclein and Aβ42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB). PMID:21048932

  13. Estimation of cerebrospinal fluid cortisol level in tuberculous meningitis

    PubMed Central

    Mahale, Rohan R.; Mehta, Anish; Uchil, Sudhir

    2015-01-01

    Background: Central nervous system (CNS) involvement in tuberculosis is around 5–10%. Of the various manifestations of CNS tuberculosis, meningitis is the most common (70–80%). Delay in diagnosis and treatment results in significant morbidity and mortality. Objective: To study the cerebrospinal fluid (CSF) cortisol levels in tubercular meningitis and compare the levels with controls. Methods: Cross-sectional, prospective, observational, hospital-based study done in 20 patients of tubercular meningitis, 20 patients of aseptic meningitis (AM) and 25 control subjects without any preexisting neurological disorders who have undergone lumbar puncture for spinal anesthesia. Results: Cortisol was detected in all 40 CSF samples of patients (100%). Mean CSF cortisol level was 8.82, 3.47 and 1.05 in tubercular meningitis, AM and controls, respectively. Mean CSF cortisol level in tubercular meningitis was significantly higher as compared to AM and controls (P < 0.0001). Conclusion: Cortisol level estimation in CSF is one of the rapid, relatively inexpensive diagnostic markers in early identification of tubercular meningitis along with CSF findings of elevated proteins, hypoglycorrhachia and lymphocytic pleocytosis. This aids in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. This is the first study on the estimation of CSF cortisol level in tuberculous meningitis. PMID:26752900

  14. A Poorly Known Cerebrospinal Fluid Shunt Complication: Miyazaki Syndrome.

    PubMed

    Caruso, Riccardo; Wierzbicki, Venceslao; Marrocco, Luigi; Pesce, Alessandro; Piccione, Emanuele

    2015-09-01

    We studied a poorly known form of cerebrospinal fluid hypotension characterized by cervical myelopathy, a considerable growth in volume of the venous plexus of the cervical spine, and absence of headache. This form was first described by Miyazaki. We reported a case brought to our attention, reviewed the literature, and formulated etiopathogenic theories that might explain all the various clinical aspects of this pathology. PMID:25913430

  15. Proteomic analysis of cerebrospinal fluid in amyotrophic lateral sclerosis

    PubMed Central

    CHEN, YAN; LIU, XIAO-HUI; WU, JIAN-JUN; REN, HUI-MING; WANG, JIAN; DING, ZHENG-TONG; JIANG, YU-PING

    2016-01-01

    The present study used comparative proteomic analysis of cerebrospinal fluid (CSF) in amyotrophic lateral sclerosis (ALS) patients in order to identify proteins that may act as diagnostic biomarkers and indicators of the pathogenesis of ALS. This analysis was performed using isobaric tags for relative and absolute quantitation (iTRAQ) technology, coupled with 2-dimensional liquid chromatography/mass spectrometry. Database for Annotation, Visualization and Integrated Discovery software was utilized for bioinformatic analysis of the data. Following this, western blotting was performed in order to examine the expression of 3 candidate proteins in ALS patients compared with healthy individuals [as a normal control (NC) group] or patients with other neurological disease (OND); these proteins were insulin-like growth factor II (IGF-2), glutamate receptor 4 (GRIA4) and leucine-rich α-2-glycoprotein 1 (LRG1). Clinical data, including gender, age, disease duration and ALS functional rating scale (ALSFRS-R) score, were also collected in the ALS patients. Multiple linear regression analysis was performed between the clinical data and the results of western blot analysis. A total of 248 distinct proteins were identified in the ALS and NC groups, amongst which a significant difference could be identified in 35 proteins; of these, 21 proteins were downregulated and 14 were upregulated. These differentially-expressed proteins were thus revealed to be associated with ALS. The western blot analysis confirmed a proportion of the data attained in the iTRAQ analysis, revealing the differential protein expression of IGF-2 and GRIA4 between the ALS and NC groups. IGF-2 was significantly downregulated in ALS patients (P=0.017) and GRIA4 was significantly upregulated (P=0.016). These results were subsequently validated in the 35-patient ALS and OND groups (P=0.002), but no significant difference was identified in LRG1 expression between these groups. GRIA4 protein expression was higher

  16. Proteomic Analysis of Cerebrospinal Fluid in Canine Cervical Spondylomyelopathy

    PubMed Central

    Martin-Vaquero, Paula; da Costa, Ronaldo C.; Allen, Matthew J.; Moore, Sarah A.; Keirsey, Jeremy K.; Green, Kari B.

    2015-01-01

    Study Design Prospective study. Objective To identify proteins with differential expression in the cerebrospinal fluid (CSF) from 15 clinically normal (control) dogs and 15 dogs with cervical spondylomyelopathy (CSM). Summary of Background Data Canine CSM is a spontaneous, chronic, compressive cervical myelopathy similar to human cervical spondylotic myelopathy. There is a limited knowledge of the molecular mechanisms underlying these conditions. Differentially expressed CSF proteins may contribute with novel information about the disease pathogenesis in both dogs and humans. Methods Protein separation was performed with two-dimensional electrophoresis. A Student’s t-test was used to detect significant differences between groups (P < 0.05). Three comparisons were made: 1) control versus CSM-affected dogs, 2) control versus non-corticosteroid treated CSM-affected dogs, and 3) non-corticosteroid treated CSM-affected versus corticosteroid treated CSM-affected dogs. Protein spots exhibiting at least a statistically significant 1.25-fold change between groups were selected for subsequent identification with capillary-liquid chromatography tandem mass spectrometry. Results A total of 96 spots had a significant average change of at least 1.25-fold in one of the three comparisons. Compared to the CSF of control dogs, CSM-affected dogs demonstrated increased CSF expression of eight proteins including vitamin D-binding protein, gelsolin, creatine kinase B-type, angiotensinogen, alpha-2-HS-glycoprotein, SPARC, calsyntenin-1, and complement C3, and decreased expression of pigment epithelium-derived factor, prostaglandin-H2 D-isomerase, apolipoprotein E, and clusterin. In the CSF of CSM-affected dogs, corticosteroid treatment increased the expression of haptoglobin, transthyretin isoform 2, cystatin C-like, apolipoprotein E, and clusterin, and decreased the expression of angiotensinogen, alpha-2-HS-glycoprotein, and gelsolin. Conclusions Many of the differentially expressed

  17. [Assessment of prealbumin in cerebrospinal fluid].

    PubMed

    Hartmann, W; Kluge, H; Zahlten, W

    1987-03-01

    The paper describes statistical relationship between prealbumin and total protein in lumbal CSF of a control group and a total group of patients with neurological diseases. The equations of the regression lines and the boundary lines of the distribution areas did not significantly differ between both groups. Therefore, prealbumin seems to be not qualified for differential diagnosis. On the other hand, its application to characterize functional states of blood-brain-CSF barrier systems is discussed. PMID:3602194

  18. Cerebrospinal fluid findings after epileptic seizures.

    PubMed

    Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

    2015-12-01

    We aimed to evaluate ictally-induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work-up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF-to-serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non-inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF-to-serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further-reaching pathological implications besides their postictal character. PMID:26575850

  19. The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy.

    PubMed

    Chen, Wenzhen; Tan, Yan; Ge, Yuxing; Chen, Yujuan; Liu, Xueyuan

    2015-11-01

    Our objective is to explore the effects of levetiracetam on the levels of neuropeptides, serum activity and concentrations of oxidative stress and inflammatory response proteins, and levels of brain injury marker in patients with refractory epilepsy. Seventy-two patients with refractory epilepsy received levetiracetam treatment. Neuropeptides galanin (GAL) and neuropeptide Y (NPY) in plasma and cerebrospinal fluid (CSF) were detected using double-antibody sandwich immunoassay and radioimmunoassay, respectively. Enzyme-linked immunosorbent assay was used to detect serum activity of paraoxonase (PON1) and serum concentrations of oxidized low-density lipoprotein (ox-LDL) and S100B. Arylesterase (ARE) activity was measured by colorimetric assay, and immune scatter turbidimetry was used to detect a high-sensitivity C-reactive protein (hs-CRP). After treatment, NPY and GAL in plasma and CSF of the patients were significantly decreased as compared to concentrations before treatment (P < 0.05). Levetiracetam reduced serum activities of PON1 and ARE (P < 0.05) and led to markedly increased serum levels of ox-LDL (P < 0.05). Serum concentrations of hs-CRP and S100B protein were significantly lower after levetiracetam administrations than before treatment (P < 0.05). Levetiracetam treatment had a clear beneficial effect on the overall quality of life (QOL) scores of the patients, as indicated by significantly improved cognitive functioning, behavior problems, emotional conditioning, physical condition, social functioning, self-assessed life quality score, self-assessed health score, and the total QOL score (P < 0.05). Levetiracetam can improve life quality of patients with refractory epilepsy, decrease NPY and GAL in plasma and cerebrospinal fluid, serum PON1 and ARE activities, and serum levels of ox-LDL, hs-CRP, and S100B. Levetiracetam therefore may be considered a drug of choice for treating refractory epilepsy. PMID:27352343

  20. Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes

    PubMed Central

    Vanderstichele, Hugo Marcel Johan; Janelidze, Shorena; Demeyer, Leentje; Coart, Els; Stoops, Erik; Herbst, Victor; Mauroo, Kimberley; Brix, Britta; Hansson, Oskar

    2016-01-01

    Background: Reduced cerebrospinal fluid (CSF) concentration of amyloid-β1-42 (Aβ1-42) reflects the presence of amyloidopathy in brains of subjects with Alzheimer’s disease (AD). Objective: To qualify the use of Aβ1-42/Aβ1-40 for improvement of standard operating procedures (SOP) for measurement of CSF Aβ with a focus on CSF collection, storage, and analysis. Methods: Euroimmun ELISAs for CSF Aβ isoforms were used to set up a SOP with respect to recipient properties (low binding, polypropylene), volume of tubes, freeze/thaw cycles, addition of detergents (Triton X-100, Tween-20) in collection or storage tubes or during CSF analysis. Data were analyzed with linear repeated measures and mixed effects models. Results: Optimization of CSF analysis included a pre-wash of recipients (e.g., tubes, 96-well plates) before sample analysis. Using the Aβ1-42/Aβ1-40 ratio, in contrast to Aβ1-42, eliminated effects of tube type, additional freeze/thaw cycles, or effect of CSF volumes for polypropylene storage tubes. ‘Low binding’ tubes reduced the loss of Aβ when aliquoting CSF or in function of additional freeze/thaw cycles. Addition of detergent in CSF collection tubes resulted in an almost complete absence of variation in function of collection procedures, but affected the concentration of Aβ isoforms in the immunoassay. Conclusion: The ratio of Aβ1-42/Aβ1-40 is a more robust biomarker than Aβ1-42 toward (pre-) analytical interfering factors. Further, ‘low binding’ recipients and addition of detergent in collection tubes are able to remove effects of SOP-related confounding factors. Integration of the Aβ1-42/Aβ1-40 ratio and ‘low-binding tubes’ into guidance criteria may speed up worldwide standardization of CSF biomarker analysis. PMID:27258423

  1. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

    PubMed Central

    2009-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

  3. Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections.

    PubMed

    Krut, Jan Jessen; Zetterberg, Henrik; Blennow, Kaj; Cinque, Paola; Hagberg, Lars; Price, Richard W; Studahl, Marie; Gisslén, Magnus

    2013-02-01

    The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis. PMID:23052602

  4. Pediatric leptomeningeal metastasis: 111In-DTPA cerebrospinal fluid flow studies.

    PubMed

    Chamberlain, M C

    1994-04-01

    Nine children (five girls and four boys) ranging in age from 1 to 18 years (median age, 12 years) with leptomeningeal metastasis were evaluated for cerebrospinal fluid compartmentalization with cerebrospinal fluid flow studies using ventricular diethylenetriaminepentaacetic acid labeled with indium 111 (111In-DTPA). Histologic diagnosis included medulloblastoma (two), primitive neuroectodermal tumor (two), acute lymphoblastic leukemia (two), pineoblastoma (one), ependymoma (one), and anaplastic astrocytoma (one). Sixteen 111In-DTPA cerebrospinal fluid flow studies were performed, of which nine demonstrated normal anterograde cerebrospinal fluid flow of radionuclide, with the following cerebrospinal fluid compartment median times to appearance, with ranges in parentheses: ventricles, 1 minute (0 to 3 minutes); cisterna magna/basal cisterns, 5 minutes (3 to 5 minutes); cervical subarachnoid space, 8 minutes (5 to 10 minutes); thoracic subarachnoid space, 15 minutes (10 to 30 minutes); lumbar subarachnoid space, 35 minutes (20 to 45 minutes); and sylvian cistern, 80 minutes (60 to 90 minutes). Blockage of normal anterograde cerebrospinal fluid flow was seen in seven 111In-DTPA cerebrospinal fluid flow studies in the following cerebrospinal fluid compartments: cervical subarachnoid space (four), lumbar subarachnoid space (two), and cisterna magna/basal cisterns (one). Five 111In-DTPA cerebrospinal fluid flow studies were performed after demonstration of cerebrospinal fluid compartmentalization and treatment with limited-field radiation therapy to involved regions; cerebrospinal fluid flow blocks resolved in three. In conclusion, cerebrospinal fluid compartmentalization, as shown by radionuclide ventriculography, is a common occurrence in pediatric leptomeningeal metastasis (four of nine patients, or 44%) and may be palliated by involved-field radiotherapy. PMID:8006365

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

    PubMed

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

    1983-09-01

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

  6. Management of Frontal Sinus Cerebrospinal Fluid Leaks and Encephaloceles.

    PubMed

    Illing, Elisa A; Woodworth, Bradford A

    2016-08-01

    Encephaloceles and cerebrospinal fluid (CSF) leaks of the frontal sinus may result from congenital, traumatic, spontaneous, or neoplastic causes. Paramount to success is adequate preoperative planning with accurate history, physical exam, endoscopy, imaging, and testing to confirm location of the leak and origin of the disease. Generally, frontal sinus CSF leaks may be addressed endoscopically with favorable anatomy, proper surgical technique, and appropriate equipment. Open surgical approaches (eg, osteoplastic flap) are often required for superior/lateral defects or if the surgeon is not experienced with endoscopic frontal sinus techniques. PMID:27450619

  7. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    NASA Astrophysics Data System (ADS)

    Gonchukov, S. A.; Lonkina, T. V.; Minaeva, S. A.; Sundukov, A. V.; Migmanov, T. E.; Lademann, J.; Darvin, M. E.; Bagratashvili, V. N.

    2014-01-01

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

  8. [Spontaneous trans-sphenoidal encephalocele presenting with nontraumatic cerebrospinal fluid rhinorrhea (case report)].

    PubMed

    Yücel, Aylin; Değirmenci, Bumin; Yilmaz, M Deniz; Altuntaş, Ali

    2004-09-01

    Encephaloceles are uncommon and can arise from congenital, traumatic, or spontaneous origins. Approximately 80% of all cerebrospinal fluid rhinorrheas are caused by head injuries. Spontaneous or nontraumatic encephaloceles or cerebrospinal fluid leaks have been the least common in most series, accounting for only 3% to 5% of all cerebrospinal fluid leaks. There is a high incidence of meningitis and brain abscess. Thus, early diagnosis is very important. We present an adult patient with uncomplicated nontraumatic cerebrospinal fluid rhinorrhea that was caused by spontaneous trans-sphenoidal encephalocele. PMID:15470620

  9. Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer's Disease Patients.

    PubMed

    Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

    2015-01-01

    Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD. PMID:25926771

  10. Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer’s Disease Patients

    PubMed Central

    Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

    2015-01-01

    Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer’s disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood–cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD. PMID:25926771

  11. Evaluation of the Production and Absorption of Cerebrospinal Fluid

    PubMed Central

    MIYAJIMA, Masakazu; ARAI, Hajime

    2015-01-01

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

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

    PubMed

    Miyajima, Masakazu; Arai, Hajime

    2015-01-01

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

  13. Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  14. Cerebrospinal fluid pressure in conscious head-down tilted rats

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

    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.

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

    PubMed Central

    2010-01-01

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

  16. Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease with 14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean Creutzfeldt-Jakob disease active surveillance program

    PubMed Central

    Lim, Jae-Sung; Kwon, Hyung-Min; Jang, Jae-Won; Ju, Young-Ran; Kim, SuYeon; Park, Young Ho; Park, So Young; Kim, SangYun

    2015-01-01

    Abstract Although Korea had a national surveillance system for Creutzfeldt-Jakob disease (CJD), it was mainly dependent on attending physician's reports. Thus, little prospective data about the epidemiology, characteristics, and final diagnoses of suspected patients were available. We have established a nationwide network for the active surveillance of patients with suspected CJD. When the requested cerebrospinal fluid (CSF) samples tested positive for 14-3-3 protein, we investigated the clinical characteristics of the corresponding patients and followed them until their final diagnoses were confirmed. A total of 218 samples were requested for CSF assays from May 2010 to August 2012, and 106 (48.6%) were positive for 14-3-3 protein. In 89 patients with complete clinical data, 38 (42.7%) were diagnosed with probable CJD and the estimated annual occurrence of CJD was 16.3 persons-per-year. The most common diagnoses of the remainder were central nervous system infection and any-cause encephalopathy. Non-CJD subjects showed worse initial consciousness levels than CJD patients. This preliminary study showed that the number of reported cases of CJD and the true positivity rates of CSF 14-3-3 protein assays were both low in Korea. An active surveillance system is urgently needed to provide the latest nationwide epidemiological data of CJD. PMID:25996401

  17. Pulsatile cerebrospinal fluid dynamics in the human brain.

    PubMed

    Linninger, Andreas A; Tsakiris, Cristian; Zhu, David C; Xenos, Michalis; Roycewicz, Peter; Danziger, Zachary; Penn, Richard

    2005-04-01

    Disturbances of the cerebrospinal fluid (CSF) flow in the brain can lead to hydrocephalus, a condition affecting thousands of people annually in the US. Considerable controversy exists about fluid and pressure dynamics, and about how the brain responds to changes in flow patterns and compression in hydrocephalus. This paper presents a new model based on the first principles of fluid mechanics. This model of fluid-structure interactions predicts flows and pressures throughout the brain's ventricular pathways consistent with both animal intracranial pressure (ICP) measurements and human CINE phase-contrast magnetic resonance imaging data. The computations provide approximations of the tissue deformations of the brain parenchyma. The model also quantifies the pulsatile CSF motion including flow reversal in the aqueduct as well as the changes in ICPs due to brain tissue compression. It does not require the existence of large transmural pressure differences as the force for ventricular expansion. Finally, the new model gives an explanation of communicating hydrocephalus and the phenomenon of asymmetric hydrocephalus. PMID:15825857

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

    PubMed

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

    1998-03-01

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

  19. Congenital cerebrospinal fluid fistula through the inner ear and meningitis.

    PubMed

    Phelps, P D; Proops, D; Sellars, S; Evans, J; Michaels, L

    1993-06-01

    Congenital deformities of the labyrinth of the inner ear can be associated with a fistulous communication between the intracranial subarachnoid space and the middle ear cavity. We describe seven such cases, six confirmed by high resolution CT and one by postmortem histological section. The seven patients all presented with meningitis although a cerebrospinal fluid fistula was demonstrated at subsequent surgery or postmortem. The lesions were bilateral in three patients, unilateral in three and probably bilateral in the postmortem case although only one temporal bone was obtained. In every case there was a dilated sac instead of the normal two and a half turn cochlea on the affected side and this was confirmed at surgery. The demonstration of the basal cochlear turn is of paramount importance in any deaf child presenting with meningitis. A true Mondini deformity with a normal basal turn and some hearing is not at risk of developing a fistula. PMID:8345296

  20. Massive Cerebrospinal Fluid Leak of the Temporal Bone

    PubMed Central

    Manno, Alessandra; Pasqualitto, Emanuela; Ciofalo, Andrea; Angeletti, Diletta; Pasquariello, Benedetta

    2016-01-01

    Cerebrospinal fluid (CSF) leakage of the temporal bone region is defined as abnormal communications between the subarachnoidal space and the air-containing spaces of the temporal bone. CSF leak remains one of the most frequent complications after VS surgery. Radiotherapy is considered a predisposing factor for development of temporal bone CSF leak because it may impair dural repair mechanisms, thus causing inadequate dural sealing. The authors describe the case of a 47-year-old man with a massive effusion of CSF which extended from the posterior and lateral skull base to the first cervical vertebrae; this complication appeared after a partial enucleation of a vestibular schwannoma (VS) with subsequent radiation treatment and second operation with total VS resection. PMID:27597915

  1. Massive Cerebrospinal Fluid Leak of the Temporal Bone.

    PubMed

    Iannella, Giannicola; Manno, Alessandra; Pasqualitto, Emanuela; Ciofalo, Andrea; Angeletti, Diletta; Pasquariello, Benedetta; Magliulo, Giuseppe

    2016-01-01

    Cerebrospinal fluid (CSF) leakage of the temporal bone region is defined as abnormal communications between the subarachnoidal space and the air-containing spaces of the temporal bone. CSF leak remains one of the most frequent complications after VS surgery. Radiotherapy is considered a predisposing factor for development of temporal bone CSF leak because it may impair dural repair mechanisms, thus causing inadequate dural sealing. The authors describe the case of a 47-year-old man with a massive effusion of CSF which extended from the posterior and lateral skull base to the first cervical vertebrae; this complication appeared after a partial enucleation of a vestibular schwannoma (VS) with subsequent radiation treatment and second operation with total VS resection. PMID:27597915

  2. Citramalic acid in cerebrospinal fluid of patients with bacterial meningitis.

    PubMed

    Perlman, S; Carr, S A

    1984-07-01

    Cerebrospinal fluid (CSF) from uninfected patients and from patients with bacterial and viral meningitis was analyzed by gas-liquid chromatography, with use of a flame ionization detector, and by gas chromatography-mass spectrometry. The resulting profiles were consistent and reproducible. Hydroxy acids were the compounds found in greatest abundance in both normal and infected CSF. Control experiments to establish the sensitivity and efficiency of the extraction and derivatization methods are also presented. Constituents of CSF from patients with bacterial meningitis differed quantitatively and qualitatively from those of CSF from uninfected patients or patients with nonbacterial infections. CSF from seven of eight patients with bacterial meningitis contained citramalic acid, a compound not previously identified in either normal or infected CSF. The implications of these findings are discussed. PMID:6145530

  3. Microscale Depletion of High Abundance Proteins in Human Biofluids using IgY14 Immunoaffinity Resin. Analysis of Human Plasma and Cerebrospinal Fluid

    SciTech Connect

    Hyung, Seok Won; Piehowski, Paul D.; Moore, Ronald J.; Orton, Daniel J.; Schepmoes, Athena A.; Clauss, Therese RW; Chu, Rosalie K.; Fillmore, Thomas L.; Brewer, Heather M.; Liu, Tao; Zhao, Rui; Smith, Richard D.

    2014-09-06

    Removal of highly abundant proteins in plasma is often carried out using immunoaffinity depletion to extend the dynamic range of measurements to lower abundance species. While commercial depletion columns are available for this purpose, they generally are not applicable to limited sample quantities (<20 µL) due to low yields stemming from losses caused by nonspecific binding to the column matrix. Additionally, the cost of the depletion media can be prohibitive for larger scale studies. Modern LC-MS instrumentation provides the sensitivity necessary to scale-down depletion methods with minimal sacrifice to proteome coverage, which makes smaller volume depletion columns desirable for maximizing sample recovery when samples are limited, as well as for reducing the expense of large scale studies. We characterized the performance of a 346 µL column volume micro-scale depletion system, using four different flow rates to determine the most effective depletion conditions for ~6 μL injections of human plasma proteins and then evaluated depletion reproducibility at the optimum flow rate condition. Depletion of plasma using a commercial 10 mL depletion column served as the control. Results showed depletion efficiency of the micro-scale column increased as flow rate decreased, and that our micro-depletion was reproducible. In an initial application, a 600 µL sample of human cerebral spinal fluid (CSF) pooled from multiple sclerosis patients was depleted and then analyzed using reversed phase liquid chromatography-mass spectrometry to demonstrate the utility of the system for this important biofluid where sample quantities are more commonly limited.

  4. Microscale depletion of high abundance proteins in human biofluids using IgY14 immunoaffinity resin: Analysis of human plasma and cerebrospinal fluid

    SciTech Connect

    Hyung, Seok Won; Piehowski, Paul D.; Moore, Ronald J.; Orton, Daniel J.; Schepmoes, Athena A.; Clauss, Therese R.; Chu, Rosalie K.; Fillmore, Thomas L.; Brewer, Heather M.; Liu, Tao; Zhao, Rui; Smith, Richard D.

    2014-09-06

    Removal of highly abundant proteins in plasma is often carried out using immunoaffinity depletion to extend the dynamic range of measurements to lower abundance species. While commercial depletion columns are available for this purpose, they generally are not applicable to limited sample quantities (<20 µL) due to low yields stemming from losses caused by nonspecific binding to the column matrix. Additionally, the cost of the depletion media can be prohibitive for larger scale studies. Modern LC-MS instrumentation provides the sensitivity necessary to scale-down depletion methods with minimal sacrifice to proteome coverage, which makes smaller volume depletion columns desirable for maximizing sample recovery when samples are limited, as well as for reducing the expense of large scale studies. We characterized the performance of a 346 µL column volume micro-scale depletion system, using four different flow rates to determine the most effective depletion conditions for ~6 μL injections of human plasma proteins and then evaluated depletion reproducibility at the optimum flow rate condition. Depletion of plasma using a commercial 10 mL depletion column served as the control. Results showed depletion efficiency of the micro-scale column increased as flow rate decreased, and that our micro-depletion was reproducible. We found, in an initial application, a 600 µL sample of human cerebral spinal fluid (CSF) pooled from multiple sclerosis patients was depleted and then analyzed using reversed phase liquid chromatography-mass spectrometry to demonstrate the utility of the system for this important biofluid where sample quantities are more commonly limited.

  5. Microscale depletion of high abundance proteins in human biofluids using IgY14 immunoaffinity resin: Analysis of human plasma and cerebrospinal fluid

    DOE PAGESBeta

    Hyung, Seok Won; Piehowski, Paul D.; Moore, Ronald J.; Orton, Daniel J.; Schepmoes, Athena A.; Clauss, Therese R.; Chu, Rosalie K.; Fillmore, Thomas L.; Brewer, Heather M.; Liu, Tao; et al

    2014-09-06

    Removal of highly abundant proteins in plasma is often carried out using immunoaffinity depletion to extend the dynamic range of measurements to lower abundance species. While commercial depletion columns are available for this purpose, they generally are not applicable to limited sample quantities (<20 µL) due to low yields stemming from losses caused by nonspecific binding to the column matrix. Additionally, the cost of the depletion media can be prohibitive for larger scale studies. Modern LC-MS instrumentation provides the sensitivity necessary to scale-down depletion methods with minimal sacrifice to proteome coverage, which makes smaller volume depletion columns desirable for maximizingmore » sample recovery when samples are limited, as well as for reducing the expense of large scale studies. We characterized the performance of a 346 µL column volume micro-scale depletion system, using four different flow rates to determine the most effective depletion conditions for ~6 μL injections of human plasma proteins and then evaluated depletion reproducibility at the optimum flow rate condition. Depletion of plasma using a commercial 10 mL depletion column served as the control. Results showed depletion efficiency of the micro-scale column increased as flow rate decreased, and that our micro-depletion was reproducible. We found, in an initial application, a 600 µL sample of human cerebral spinal fluid (CSF) pooled from multiple sclerosis patients was depleted and then analyzed using reversed phase liquid chromatography-mass spectrometry to demonstrate the utility of the system for this important biofluid where sample quantities are more commonly limited.« less

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

    PubMed

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

    2012-03-15

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2009-11-01

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

  9. Cysticercus Antigens in Cerebrospinal Fluid Samples from Patients with Neurocysticercosis

    PubMed Central

    Pardini, Alessandra Xavier; Vaz, Adelaide José; Machado, Luis Dos Ramos; Livramento, José Antônio

    2001-01-01

    Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n = 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried out with the anti-Tso, anti-Tcra, and anti-Tcra <30 kDa showed sensitivities of 81.2, 90, and 95.8% and specificities of 82, 98, and 100%, respectively. The 14- and 18-kDa low-molecular-weight peptides were only detected in CSF samples from patients with NC by immunoblotting with anti-Tso and anti-Tcra sera. Because of the importance of the diagnosis and prognosis of cysticercosis, the detection of antigens may contribute as an additional marker to the study and clarification of the parasite-host relationship. PMID:11526181

  10. Comparative Analysis of Technologies for Quantifying Extracellular Vesicles (EVs) in Clinical Cerebrospinal Fluids (CSF).

    PubMed

    Akers, Johnny C; Ramakrishnan, Valya; Nolan, John P; Duggan, Erika; Fu, Chia-Chun; Hochberg, Fred H; Chen, Clark C; Carter, Bob S

    2016-01-01

    Extracellular vesicles (EVs) have emerged as a promising biomarker platform for glioblastoma patients. However, the optimal method for quantitative assessment of EVs in clinical bio-fluid remains a point of contention. Multiple high-resolution platforms for quantitative EV analysis have emerged, including methods grounded in diffraction measurement of Brownian motion (NTA), tunable resistive pulse sensing (TRPS), vesicle flow cytometry (VFC), and transmission electron microscopy (TEM). Here we compared quantitative EV assessment using cerebrospinal fluids derived from glioblastoma patients using these methods. For EVs <150 nm in diameter, NTA detected more EVs than TRPS in three of the four samples tested. VFC particle counts are consistently 2-3 fold lower than NTA and TRPS, suggesting contribution of protein aggregates or other non-lipid particles to particle count by these platforms. While TEM yield meaningful data in terms of the morphology, its particle count are consistently two orders of magnitude lower relative to counts generated by NTA and TRPS. For larger particles (>150 nm in diameter), NTA consistently detected lower number of EVs relative to TRPS. These results unveil the strength and pitfalls of each quantitative method alone for assessing EVs derived from clinical cerebrospinal fluids and suggest that thoughtful synthesis of multi-platform quantitation will be required to guide meaningful clinical investigations. PMID:26901428

  11. Comparative Analysis of Technologies for Quantifying Extracellular Vesicles (EVs) in Clinical Cerebrospinal Fluids (CSF)

    PubMed Central

    Akers, Johnny C.; Ramakrishnan, Valya; Nolan, John P.; Duggan, Erika; Fu, Chia-Chun; Hochberg, Fred H.; Chen, Clark C.; Carter, Bob S.

    2016-01-01

    Extracellular vesicles (EVs) have emerged as a promising biomarker platform for glioblastoma patients. However, the optimal method for quantitative assessment of EVs in clinical bio-fluid remains a point of contention. Multiple high-resolution platforms for quantitative EV analysis have emerged, including methods grounded in diffraction measurement of Brownian motion (NTA), tunable resistive pulse sensing (TRPS), vesicle flow cytometry (VFC), and transmission electron microscopy (TEM). Here we compared quantitative EV assessment using cerebrospinal fluids derived from glioblastoma patients using these methods. For EVs <150 nm in diameter, NTA detected more EVs than TRPS in three of the four samples tested. VFC particle counts are consistently 2–3 fold lower than NTA and TRPS, suggesting contribution of protein aggregates or other non-lipid particles to particle count by these platforms. While TEM yield meaningful data in terms of the morphology, its particle count are consistently two orders of magnitude lower relative to counts generated by NTA and TRPS. For larger particles (>150 nm in diameter), NTA consistently detected lower number of EVs relative to TRPS. These results unveil the strength and pitfalls of each quantitative method alone for assessing EVs derived from clinical cerebrospinal fluids and suggest that thoughtful synthesis of multi-platform quantitation will be required to guide meaningful clinical investigations. PMID:26901428

  12. Monoamines in the brain cerebrospinal fluid of facial pain patients.

    PubMed Central

    Bouckoms, A. J.; Sweet, W. H.; Poletti, C.; Lavori, P.; Carr, D.; Matson, W.; Gamache, P.; Aronin, N.

    1992-01-01

    The purpose of the study was to assay monoamines in cerebrospinal fluid (CSF) obtained from the trigeminal cistern of 64 patients with intractable facial pain. The CSF was analyzed for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), end-product markers of activity for the dopamine, serotonin, and norepinephrine systems, respectively. HVA averaged 121 ng/mL in these facial pain patients, compared to 150 to 550 ng/mL in 10 studies of ventricular brain CSF in assorted psychiatric and pain patients. 5-HIAA averaged 29 to ng/mL in our facial pain patients compared to 60 to 120 ng/mL in nine studies of ventricular brain CSF in assorted psychiatric and neurological patients. Trigeminal cistern CSF MHPG averaged 9 ng/mL, similar to the range of 13 studies of lumbar CSF of assorted psychiatric and pain diagnoses. These results indicate that (1) the electrochemical detection method provides a unique way of accurately measuring nanogram concentrations of multiple monoamines in a little as 0.25 mL of CSF; (2) trigeminal cistern and posterior fossa brain CSF monoamine metabolites reflect a different profile of dopaminergic and serotonergic functioning in these facial pain patients from that previously reported with lumbar CSF measurements of other patients; and (3) trigeminal sensory ganglion or brain dopamine and serotonin systems may be concomitantly dysfunctional in intractable facial pain. PMID:7504420

  13. Postoperative Cerebrospinal Fluid Leakage Associated With Total En Bloc Spondylectomy.

    PubMed

    Yokogawa, Noriaki; Murakami, Hideki; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Hayashi, Hiroyuki; Ishii, Takayoshi; Igarashi, Takashi; Fang, Xiang; Tsuchiya, Hiroyuki

    2015-07-01

    Cerebrospinal fluid (CSF) leakage is a serious postoperative complication associated with total en bloc spondylectomy. The authors examined the risk factors for CSF leakage after this procedure. A total of 72 patients underwent total en bloc spondylectomy at the authors' institution between May 2010 and April 2013. Postoperative CSF leakage was observed in 17 of the 72 patients (23.6%). The results of univariate analysis suggested that age 54 years or older, preoperative surgical site irradiation, resection of 3 or more vertebral bodies, and dural injury were significant risk factors for postoperative CSF leakage after total en bloc spondylectomy. Multivariate analysis showed that preoperative surgical site irradiation was the only significant risk factor for postoperative CSF leakage (adjusted odds ratio, 5.22; 95% confidence interval, 1.03-26.45, P=.046). The authors also assessed the course of treatment for postoperative CSF leakage in each patient. Of 17 patients with postoperative CSF leakage, 13 recovered without further complications, but 4 required reoperation (2 for wound dehiscence, 1 for surgical site infection, and 1 for severe intracranial hypotension). All 4 patients who required reoperation had a history of surgical site irradiation. Thus, this study suggests that careful consideration should be given to postoperative CSF leakage in patients with a history of surgical site irradiation. These findings may contribute to the management of postoperative CSF leakage associated with total en bloc spondylectomy and supplement the information given to the patient in the process of obtaining informed consent. PMID:26186316

  14. Short-term stability of Borrelia garinii in cerebrospinal fluid.

    PubMed

    Berenová, Dagmar; Krsek, Daniel; Šípková, Lenka; Lukavská, Alena; Malý, Marek; Kurzová, Zuzana; Hořejší, Jan; Kodym, Petr

    2016-01-01

    The aim of our study was to find out the optimal conditions for short-term storage of cerebrospinal fluid (CSF) samples for direct diagnosis of Lyme disease. A mixture of Borrelia-negative CSFs spiked with a defined amount of cultured Borrelia garinii was used. Borrelia stability was investigated over 7 days at four different temperatures [room temperature (RT), +4, -20 and -70 °C]. Quantitative changes in CSF Borrelia were measured by quantitative PCR (qPCR), and morphological changes in the spirochetes were observed by transmission electron microscopy (TEM). These qPCR results were statistically evaluated. We found +4 °C to be an optimal temperature for short-term storage of CSF samples intended for TEM observation. There was no significant difference between the temperatures tested in the average quantity of Borrelia measured by qPCR. On the contrary, electron optical diagnosis of frozen samples and samples stored at RT showed destructive morphological changes and decreased spirochete counts. Our results show that optimal conditions for the pre-analytical phase of investigation of one type of material can differ depending on the diagnostic method employed. PMID:26104540

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

    PubMed

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

    1985-05-01

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

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

    PubMed

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

    2016-01-01

    Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. PMID:26545630

  17. Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents

    PubMed Central

    Bradley, Kailyn A. L.; Mao, Xiangling; Case, Julia A. C.; Kang, Guoxin; Shungu, Dikoma C.; Gabbay, Vilma

    2016-01-01

    Background Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. Methods Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. Results Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1, 41) = 6.98, p = .01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. Conclusions Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function. PMID:26802978

  18. Endoscopic Management of Cerebrospinal Fluid Rhinorrhea: The Charing Cross Experience

    PubMed Central

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

    2013-01-01

    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 < 0.05). Fifty percent of spontaneous leaks were from the cribriform plate, 22% sphenoid, 14% ethmoid, and 14% frontal sinus. In the traumatic CSF leak group: 33.3% were from the cribriform plate, 33.3% sphenoid, 22.2% ethmoid, and 11.1% frontal. Conclusion Endoscopic CSF fistula closure is a safe and effective operation. All sites of leak can be accessed endoscopically. We recommend the use of an anatomic three-layered closure in difficult cases. PMID:24436890

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

    NASA Astrophysics Data System (ADS)

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

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

  20. Vitamin B6 in Plasma and Cerebrospinal Fluid of Children

    PubMed Central

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

    2015-01-01

    Background Over the past years, the essential role of vitamin B6 in brain development and functioning has been recognized and genetic metabolic disorders resulting in functional vitamin B6 deficiency have been identified. However, data on B6 vitamers in children are scarce. Materials and Methods B6 vitamer concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF) of 70 children with intellectual disability were determined by ultra performance liquid chromatography-tandem mass spectrometry. For ethical reasons, CSF samples could not be obtained from healthy children. The influence of sex, age, epilepsy and treatment with anti-epileptic drugs, were investigated. Results The B6 vitamer composition of plasma (pyridoxal phosphate (PLP) > pyridoxic acid > pyridoxal (PL)) differed from that of CSF (PL > PLP > pyridoxic acid > pyridoxamine). Strong correlations were found for B6 vitamers in and between plasma and CSF. Treatment with anti-epileptic drugs resulted in decreased concentrations of PL and PLP in CSF. Conclusion We provide concentrations of all B6 vitamers in plasma and CSF of children with intellectual disability (±epilepsy), which can be used in the investigation of known and novel disorders associated with vitamin B6 metabolism as well as in monitoring of the biochemical effects of treatment with vitamin B6. PMID:25760040

  1. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

    Bottan, Simone; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2012-06-01

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

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

    PubMed Central

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

    2015-01-01

    Neurochemical biomarkers are urgently sought in ALS. Metabolomic analysis of cerebrospinal fluid (CSF) using proton nuclear magnetic resonance (1H-NMR) spectroscopy is a highly sensitive method capable of revealing nervous system cellular pathology. The 1H-NMR CSF metabolomic signature of ALS was sought in a longitudinal cohort. Six-monthly serial collection was performed in ALS patients across a range of clinical sub-types (n = 41) for up to two years, and in healthy controls at a single time-point (n = 14). A multivariate statistical approach, partial least squares discriminant analysis, was used to determine differences between the NMR spectra from patients and controls. Significantly predictive models were found using those patients with at least one year's interval between recruitment and the second sample. Glucose, lactate, citric acid and, unexpectedly, ethanol were the discriminating metabolites elevated in ALS. It is concluded that 1H-NMR captured the CSF metabolomic signature associated with derangements in cellular energy utilization connected with ALS, and was most prominent in comparisons using patients with longer disease duration. The specific metabolites identified support the concept of a hypercatabolic state, possibly involving mitochondrial dysfunction specifically. Endogenous ethanol in the CSF may be an unrecognized novel marker of neuronal tissue injury in ALS. PMID:26121274

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

    PubMed

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

    2015-01-01

    Neurochemical biomarkers are urgently sought in ALS. Metabolomic analysis of cerebrospinal fluid (CSF) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy is a highly sensitive method capable of revealing nervous system cellular pathology. The (1)H-NMR CSF metabolomic signature of ALS was sought in a longitudinal cohort. Six-monthly serial collection was performed in ALS patients across a range of clinical sub-types (n = 41) for up to two years, and in healthy controls at a single time-point (n = 14). A multivariate statistical approach, partial least squares discriminant analysis, was used to determine differences between the NMR spectra from patients and controls. Significantly predictive models were found using those patients with at least one year's interval between recruitment and the second sample. Glucose, lactate, citric acid and, unexpectedly, ethanol were the discriminating metabolites elevated in ALS. It is concluded that (1)H-NMR captured the CSF metabolomic signature associated with derangements in cellular energy utilization connected with ALS, and was most prominent in comparisons using patients with longer disease duration. The specific metabolites identified support the concept of a hypercatabolic state, possibly involving mitochondrial dysfunction specifically. Endogenous ethanol in the CSF may be an unrecognized novel marker of neuronal tissue injury in ALS. PMID:26121274

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

    PubMed Central

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

    2016-01-01

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

  7. Visualization of the cerebrospinal fluid drainage into the Galen's vein.

    PubMed

    Hashimoto, P H; Gotow, T; Ichimura, T; Nakatani, T; Takasu, N; Kodaka, R; Sumitani, S; Fukuda, T

    1985-04-01

    Arachnoid granulations are not always present in lower mammals and primate newborns. In order to visualize the route for the cerebrospinal fluid (CSF) to drain into the venous system, horseradish peroxidase (HRP) was injected into the lateral ventricle or cisterna cerebellomedullaris of the mouse and rat. From 30 to 60 min after the commencing of a slow infusion for 15-30 min of 0.05-0.1 ml solution containing 10-20 mg HRP, the mouse, whose skull had been exposed, was dropped into cold acetone at dry ice temperature; other animals were fixed by perfusion with aldehyde solution. The frozen head was dissected in a cryostat kept at -18 degrees C to remove the skull, but leave the dura mater and the falx cerebri. The brain with meninges was cut into 30-45 microns sagittal sections in the cryostat, and processed for peroxidase reaction. The perfusion-fixed brains were used for scanning electron microscopy and for electron microscope observation of the tracer. The reaction product was found within fenestrated venous capillaries of the choroid plexus. The route for the HRP in the CSF to drain into the sinus rectus via the vena choroidea and vena cerebri magna was directly visualized in the mouse. PMID:4038002

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

    PubMed

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

    2014-08-28

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

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

    PubMed Central

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

    2014-01-01

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

  10. Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis.

    PubMed

    Perlejewski, Karol; Bukowska-Ośko, Iwona; Nakamura, Shota; Motooka, Daisuke; Stokowy, Tomasz; Płoski, Rafał; Rydzanicz, Małgorzata; Zakrzewska-Pniewska, Beata; Podlecka-Piętowska, Aleksandra; Nojszewska, Monika; Gogol, Anna; Caraballo Cortés, Kamila; Demkow, Urszula; Stępień, Adam; Laskus, Tomasz; Radkowski, Marek

    2016-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system of unknown etiology. However, some infectious agents have been suggested to play a significant role in its pathogenesis. Next-generation sequencing (NGS) and metagenomics can be employed to characterize microbiome of MS patients and to identify potential causative pathogens. In this study, 12 patients with idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system were studied: one patient had clinically isolated syndrome, one patient had recurrent optic neuritis, and ten patients had multiple sclerosis (MS). In addition, there was one patient with other non-inflammatory neurological disease. Cerebrospinal fluid (CSF) was sampled from all patients. RNA was extracted from CSF and subjected to a single-primer isothermal amplification followed by NGS and comprehensive data analysis. Altogether 441,608,474 reads were obtained and mapped using blastn. In a CSF sample from the patient with clinically isolated syndrome, 11 varicella-zoster virus reads were found. Other than that similar bacterial, fungal, parasitic, and protozoan reads were identified in all samples, indicating a common presence of contamination in metagenomics. In conclusion, we identified varicella zoster virus sequences in one out of the 12 patients with IIDD, which suggests that this virus could be occasionally related to the MS pathogenesis. A widespread bacterial contamination seems inherent to NGS and complicates the interpretation of results. PMID:27311319

  11. [Cerebrospinal fluid markers in early diagnosis of Alzheimer dementia].

    PubMed

    Wiltfang, Jens

    2015-04-01

    Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) is meanwhile validated on S3 evidence level and international dementia guidelines like those of the German neuropsychiatric associations (DGPPN, DGN; http://www.DGPPN.de) recommend CSF-NDD for the improved early and differential diagnostics of multigenetic (sporadic) Alzheimer's Dementia (AD). CSF-NDD does also offer a predictive diagnosis of incipient AD for high-risk patients when they are still within the prodromal stage of mild cognitive impairment (MCI). But since currently no (secondary) preventive therapy of AD is available, the use of CSF-NDD for the predictive molecular diagnosis of AD is not recommended by the latter guidelines. However, molecular diagnostics of preclinical AD by CSF-NDD and/or [18F]Amyloid-PET has meanwhile gained high clinical relevance for therapeutic clinical research, as this novel clinical model allows to systematically screen for promising (secondary) preventive therapy options. Moreover, future blood based neurochemical diagnostics of preclinical or early AD by means of multiplex assays seems to be promising. However, so far blood assays were not consistently validated by independent research groups and in contrast to CSF-NDD a blood-based diagnosis of AD is not yet available. PMID:25791051

  12. A novel method to study cerebrospinal fluid dynamics in rats

    PubMed Central

    Karimy, Jason K.; Kahle, Kristopher T.; Kurland, David B.; Yu, Edward; Gerzanich, Volodymyr; Simard, J. Marc

    2014-01-01

    Background Cerebrospinal fluid (CSF) flow dynamics play critical roles in both the immature and adult brain, with implications for neurodevelopment and disease processes such as hydrocephalus and neurodegeneration. Remarkably, the only reported method to date for measuring CSF formation in laboratory rats is the indirect tracer dilution method (a.k.a., ventriculocisternal perfusion), which has limitations. New Method Anesthetized rats were mounted in a stereotaxic apparatus, both lateral ventricles were cannulated, and the Sylvian aqueduct was occluded. Fluid exited one ventricle at a rate equal to the rate of CSF formation plus the rate of infusion (if any) into the contralateral ventricle. Pharmacological agents infused at a constant known rate into the contralateral ventricle were tested for their effect on CSF formation in real-time. Results The measured rate of CSF formation was increased by blockade of the Sylvian aqueduct but was not changed by increasing the outflow pressure (0–3 cm of H2O). In male Wistar rats, CSF formation was age-dependent: 0.39±0.06, 0.74±0.05, 1.02±0.04 and 1.40±0.06 µL/min at 8, 9, 10 and 12 weeks, respectively. CSF formation was reduced 57% by intraventricular infusion of the carbonic anhydrase inhibitor, acetazolamide. Comparison with existing methods Tracer dilution methods do not permit ongoing real-time determination of the rate of CSF formation, are not readily amenable to pharmacological manipulations, and require critical assumptions. Direct measurement of CSF formation overcomes these limitations. Conclusions Direct measurement of CSF formation in rats is feasible. Our method should prove useful for studying CSF dynamics in normal physiology and disease models. PMID:25554415

  13. Postoperative Low-Flow Cerebrospinal Fluid Leak of Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma

    PubMed Central

    Zhan, Rucai; Chen, Songyu; Xu, Shujun; Liu, James K.; Li, Xingang

    2015-01-01

    Abstract To assess the effectiveness of continuous lumbar drainage (LD) for management of postoperative cerebrospinal fluid leaks after endoscopic endonasal transsphenoidal approach for resection of pituitary adenoma. Three hundred eighty-four medical records of patients who were admitted to our institute during a 2.5-year period were retrospectively reviewed, 33 of them experienced low-flow cerebrospinal fluid leak postoperatively. If LD was used, all patients with low-flow cerebrospinal fluid leak were classified into 2 groups, lumbar drained group and conservatively treated group. The age, sex, management of cerebrospinal fluid leaks, and related complications were reviewed. Statistical comparisons between the 2 groups were made using SPSS 19.0 (IBM Corp, Armonk, NY). The differences were considered statistically significant if the P value was less than 0.05. Thirty-three of 384 (8.6%) experienced low-flow postoperative cerebrospinal fluid leaks. Cured rate of cerebrospinal fluid leak was 94.4% (17/18) in continuous lumbar drained group, and 93.3% (14/15) in control group. There were 2 (11.2%) patients who developed meningitis in the LD group and 1 (5.6%) patient in the control group. One patient required endoscopic repair of skull base because of persistent cerebrospinal fluid leak in both groups, with the rates of 5.6% and 6.7%, respectively. There was no significant difference noted in each rate in both groups. Placement of LD may not be necessary for the management of low-flow postoperative cerebrospinal fluid leak after using endoscopic endonasal transsphenoidal approach to pituitary adenoma. PMID:26080170

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

    NASA Astrophysics Data System (ADS)

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

    1982-05-01

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

  15. A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease.

    PubMed

    Khan, Wasim; Aguilar, Carlos; Kiddle, Steven J; Doyle, Orla; Thambisetty, Madhav; Muehlboeck, Sebastian; Sattlecker, Martina; Newhouse, Stephen; Lovestone, Simon; Dobson, Richard; Giampietro, Vincent; Westman, Eric; Simmons, Andrew

    2015-01-01

    In this exploratory neuroimaging-proteomic study, we aimed to identify CSF proteins associated with AD and test their prognostic ability for disease classification and MCI to AD conversion prediction. Our study sample consisted of 295 subjects with CSF multi-analyte panel data and MRI at baseline downloaded from ADNI. Firstly, we tested the statistical effects of CSF proteins (n = 83) to measures of brain atrophy, CSF biomarkers, ApoE genotype and cognitive decline. We found that several proteins (primarily CgA and FABP) were related to either brain atrophy or CSF biomarkers. In relation to ApoE genotype, a unique biochemical profile characterised by low CSF levels of Apo E was evident in ε4 carriers compared to ε3 carriers. In an exploratory analysis, 3/83 proteins (SGOT, MCP-1, IL6r) were also found to be mildly associated with cognitive decline in MCI subjects over a 4-year period. Future studies are warranted to establish the validity of these proteins as prognostic factors for cognitive decline. For disease classification, a subset of proteins (n = 24) combined with MRI measurements and CSF biomarkers achieved an accuracy of 95.1% (Sensitivity 87.7%; Specificity 94.3%; AUC 0.95) and accurately detected 94.1% of MCI subjects progressing to AD at 12 months. The subset of proteins included FABP, CgA, MMP-2, and PPP as strong predictors in the model. Our findings suggest that the marker of panel of proteins identified here may be important candidates for improving the earlier detection of AD. Further targeted proteomic and longitudinal studies would be required to validate these findings with more generalisability. PMID:26284520

  16. Physical properties of cerebrospinal fluid of relevance to shunt function. 2: The effect of protein upon CSF surface tension and contact angle.

    PubMed

    Brydon, H L; Hayward, R; Harkness, W; Bayston, R

    1995-01-01

    CSF surface tension has received little study, and yet it will effect the pressure at which shunt valves operate, and by influencing the degree of hydrophobicity (contact angle) will alter the attraction between bacteria and neurosurgical prostheses. A study is therefore presented of the effect of protein content upon the surface tension of CSF and its contact angle to silicone rubber. Both of these quantities fell throughout the normal range of CSF protein, but above 1 g/l, additional protein had little effect, and the results obtained were similar to that reported for plasma. The effect of surface tension on the opening and closing pressures of hydrocephalus shunt valves and of contact angle in the adhesion of bacteria to neurosurgical implants is discussed. PMID:8561937

  17. High-voltage isoelectric focusing in ultrathin gels and enzyme-amplified immunoassay: a new method for analysis of cerebrospinal fluid proteins.

    PubMed

    Kjellin, K G; Hallander, L B

    1982-01-01

    A procedure using high-voltage isoelectric focusing (IF) in ultrathin (02. mm) gels and enzyme-amplified immuno-sandwich assay was elaborated to get optimal IF separation conditions, to avoid CSF concentration, e.g. by ultrafiltration preceding IF with the risk of unequal protein losses, to minimize the amounts of CSF and expensive reagents needed, especially antibodies and to shorten the analysis time, including the selective detection of proteins. The high voltage (2000-3000 V/10 cm) and efficient cooling during IF were obtained using ECPS 3000/150 and FBE 3000 (Pharmacia, Sweden). Ampholytes (Pharmalytes) of different pI intervals were used. The CSF and (diluted) serum samples were microdialysed in polyacrylamide gel before IF to minimize band curvature and to obtain optimal resolution. The IF separation was performed in about 1 h. Owing to the rapid fixation of ultrathin gels after IF, full use could be made of the high-voltage resolving capacity. The thin gels also made histochemical techniques applicable. Different immunological identification assays have been tested. An enzyme-amplified (alkaline phosphatase) immuno-sandwich method was found to be very sensitive and selective, and has so far given the best results. Many proteins in the same sample, applied as a line on the gel before IF, could be detected by overlaying antibody-soaked membrane strips. Furthermore, one specific protein could be examined in many samples simultaneously by overlaying or immersion of diluted antibody solutions. A few microlitres of unconcentrated CSF and diluted serum were used for the analysis performed within 1 day. The findings for albumin, transferrin and IgG in CSF and sera from patients with different neurological diseases, especially including cases with "normal" CSF, barrier damage, degenerative and demyelinating disorders, have been compared with the corresponding protein-stained (Coomassie R-250) patterns where the CSF had been concentrated by a special vacuum

  18. A 34-Day-Old With Fever, Cerebrospinal Fluid Pleocytosis, and Staphylococcus aureus Bacteremia.

    PubMed

    Horner, Kimberly; Yamada, Masaki; Zuccoli, Giulio; Rosenberg, Stacy; Greene, Stephanie; Vellody, Kishore; Zuckerbraun, Noel S

    2016-01-01

    A 34-day-old previously healthy boy born full term presented to the emergency department with fever at home (38.1°C), fussiness, and decreased oral intake for 1 day. He was difficult to console at home. He had decreased oral intake without emesis, diarrhea, or a change in urine output. He did not have rhinorrhea, cough, or increased work of breathing noted by parents. He lived at home with his parents and 13-year-old brother, did not attend day care, and had no sick contacts. On examination, he was fussy but consolable. He was febrile to 39.3°C, tachycardic (180 beats per minute), and tachypneic (64 breaths per minute), with mottling and a capillary refill of 3 seconds. The remainder of his examination was normal, without an infectious focus for his fever. A complete blood cell count with differential revealed leukocytosis. A basic metabolic panel was normal. A catheter urinalysis was normal. Cerebrospinal fluid examination yielded pleocytosis, low glucose, and elevated protein. Blood cultures were persistently positive with methicillin-sensitive Staphylococcus aureus, but cerebrospinal fluid cultures remained negative. We present his case, management, and ultimate diagnosis. PMID:26644490

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

    PubMed Central

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

    2011-01-01

    Cerebrospinal fluid (CSF) samples from 33 patients with Alzheimer dementia (AD), 21 patients with mild cognitive impairment who converted to AD during followup (MCI-AD), 25 patients with stable mild cognitive impairment (MCI-stable), and 16 nondemented subjects (ND) were analyzed with a chemiluminescence immunoassay to assess the levels of the mitogen-activated protein kinase ERK1/2 (extracellular signal-regulated kinase 1/2). The results were evaluated in relation to total Tau (tTau), phosphorylated Tau (pTau), and beta-amyloid 42 peptide (Aβ42). CSF-ERK1/2 was significantly increased in the AD group as compared to stable MCI patients and the ND group. Western blot analysis of a pooled cerebrospinal fluid sample revealed that both isoforms, ERK1 and ERK2, and low amounts of doubly phosphorylated ERK2 were detectable. As a predictive diagnostic AD biomarker, CSF-ERK1/2 was inferior to tTau, pTau, and Aβ42. PMID:22145083

  20. [Diagnosis of cerebrospinal fluid leakages by gamma-cisternography].

    PubMed

    Oberson, R

    1976-01-01

    Cerebrospinal fluid (CSF) leakages either secondary (traumatic) or spontaneous (non-traumatic) are first considered in their frequency and origin. The exact topography of the various meningeal and cranial lesions involved are difficult to assess particularly in the most important groups of persistant traumatic CSF rhinorrhea and recurrent meningitis. Among the various diagnostic approaches, direct observation is always necessary, but of limited value. Standard X-rays must be followed by multidirectionnal tomography (Polytome) and, whenever available, computed tomodensitography of the base of the skull. Brain pneumography provides a thorough setting fourth of the congenital or acquired cerebral lesions as well as the new cranio-meningeal conditions. Difficulties encountered with the techniques of subdurography and Pantopaque injection are underlined. Three radioisotope techniques are considered. 1) The earlier technique of cotton-pledgets only shows the external orifice. 2) The recent proposal of nuclide cranial subdurography is criticized for ignoring the leptomeningeal bag. 3) Radioisotope cisternography (RIC) or gamma-cisternography is described more precisely. It remains the most complete and appropriate method for observing the natural behaviour of the leakage. RIC with fistulography is performed through suboccipital injection of 99mTc-DTPA. RIC provides essential clues on the relative importance of associated dynamic disturbances of the third circulation and morphological changes of its anatomical bed (stenoses and widenings of the ependymal and leptomeningeal spaces). If present, the leakage may be directly shown on the RIC pictures. If rhinorrhea is abundant, there is no difficulty in assessing side and site of the fistula. If rhinorrhea is occult, dubious or intermittent, diagnosis is often difficult. There are also indirect signs of rhinorrhea: leptomeningeal dilatation near a frontal or ethmoidal fracture, contamination of the rhinopharynx, examination of

  1. Clearance of valproic acid from cerebrospinal fluid in anesthetized rabbit.

    PubMed

    Artru, A A; Adkinson, K D; Powers, K M; Shen, D D

    1994-07-01

    Clearance of valproic acid from brain tissue is believed to occur via a carrier-mediated system(s). The present study was designed to determine whether clearance was capacity-limited (saturable) and whether it occurred primarily at the choroid plexus. Ten rabbits were anesthetized with halothane and surgically prepared for ventriculocisternal perfusion. In group 1 (n = 5) valproic acid was added to blue dextran-containing mock cerebrospinal fluid (CSF) to achieve concentrations of 5, 20, 100, and 500 micrograms.ml-1. The mixture was infused through needles in both cerebral ventricles. The purpose of this group was to determine whether over a large range (100x) of valproic acid concentrations, clearance from CSF was capacity limited (saturable). In group 2 (n = 5) valproic acid concentrations were 3, 10, and 30 microgram.ml-1 and infusion was into the left cerebral ventricle only. The purposes of this group were to determine (a) the magnitude of valproic acid clearance for the "clinical" range of valproic acid in CSF (10-30 micrograms.ml-1), and (b) whether clearance of valproic acid was changed by perfusion across a portion of the choroid plexus surface area (group 2) as compared with perfusion across the entire choroid plexus surface area (group 1). In both groups the percent extraction of valproic acid was calculated from the concentration ratio (valproic acid)out/(valproic acid)in corrected for the rate of CSF formation. In group 1 the percent extraction of valproic acid was 93 +/- 2% (mean +/- SD) at 5 micrograms.ml-1 and stabilized within the range of 58-70% (individual values) at the higher inflow concentrations of valproic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7521700

  2. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines

    PubMed Central

    Warrington, Junie P

    2015-01-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ∼13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R2 = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  3. Evaluation of Cerebrospinal Fluid Assay Variability in Alzheimer's Disease

    PubMed Central

    White, Matthew T.; Shaw, Leslie M.; Xie, Sharon X.

    2016-01-01

    SUMMARY Studies of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) have indicated that much of the variability observed in the biomarkers may be due to measurement error. Biomarkers are often obtained with measurement error, which may make the diagnostic biomarker appear less effective than it truly is. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, technical replicates of CSF biomarkers are available; the National Alzheimer's Coordinating Center database contains longitudinal replicates of CSF biomarkers. We focus on the area under the receiver operating characteristic curve (AUC) as the measure of diagnostic effectiveness for differentiating AD from normal cognition using CSF biomarkers and compare AUC estimates obtained by a more standard, naïve method (which uses a single observation per subject and ignores measurement error) to a maximum likelihood (ML) based method (which uses all replicates per subject and adjusts for measurement error). The choice of analysis method depends upon the noise to signal ratio (i.e., the magnitude of the measurement error variability relative to the true biomarker variability); moderate to high ratios may significantly bias the naïve AUC estimate, and the ML-based method would be preferred. The noise to signal ratios were low for the ADNI biomarkers but high for the tTau and pTau biomarkers in NACC. Correspondingly, the naïve and ML-based AUC estimates were nearly identical in the ADNI data but dissimilar for the tTau and pTau biomarkers in the NACC data. Therefore, using the naïve method is adequate for analysis of CSF biomarkers in the ADNI study, but the ML method is recommended for the NACC data. PMID:26890778

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

    PubMed

    Warrington, Junie P

    2015-11-01

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

  5. Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

    PubMed Central

    Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

    2016-01-01

    The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

  6. Surgical challenge: endoscopic repair of cerebrospinal fluid leak

    PubMed Central

    2012-01-01

    Background Cerebrospinal fluid leaks (CSF) result from an abnormal communication between the subarachnoid space and the extracranial space. Approximately 90% of CSF leak at the anterior skull base manifests as rhinorrhea and can become life-threatening condition. Endoscopic sinus surgery (ESS) has become a common otolaryngologist procedure. The aim of this article is to consider our experience and to evaluate the outcomes in patients who underwent a purely endoscopic repair of CSF leaks of the anterior skull base. Findings Retrospective chart review was performed of all patients surgically treated for CSF leaks presenting to the Section of Nasal and Sinus Disorders at the Service of ENT–Head and Neck Surgery, University Hospital Complex of Santiago de Compostela (CHUS), between 2004 and 2010. A total of 30 patients who underwent repair CSF leak by ESS. The success rate was 93.4% at the first attempt; only two patients (6.6%) required a second surgical procedure, and none of it was necessary to use a craniotomy for closure. Follow-up periods ranged from 4 months to 6 years. Conclusion Identifying the size, site, and etiology of the CSF leak remains the most important factor in the surgical success. It is generally accepted that the ESS have made procedures minimally invasive, and CSF leak is now one of its well-established indications with low morbidity and high success rate, with one restriction for fistulas of the posterior wall of the frontal sinus should be repaired in conjunction with open techniques. PMID:22925201

  7. Independent information from cerebrospinal fluid amyloid-β and florbetapir imaging in Alzheimer's disease.

    PubMed

    Mattsson, Niklas; Insel, Philip S; Donohue, Michael; Landau, Susan; Jagust, William J; Shaw, Leslie M; Trojanowski, John Q; Zetterberg, Henrik; Blennow, Kaj; Weiner, Michael W

    2015-03-01

    Reduced cerebrospinal fluid amyloid-β42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree and may represent partly different aspects of the underlying Alzheimer's disease pathology. The goal of this study was therefore to test if cerebrospinal fluid and positron emission tomography amyloid-β biomarkers are independently related to other Alzheimer's disease markers, and to examine individuals who are discordantly classified by these two biomarker modalities. Cerebrospinal fluid and positron emission tomography amyloid-β were measured at baseline in 769 persons [161 healthy controls, 68 subjective memory complaints, 419 mild cognitive impairment and 121 Alzheimer's disease dementia, mean age 72 years (standard deviation 7 years), 47% females] and used to predict diagnosis, APOE ε4 carriage status, cerebral blood flow, cerebrospinal fluid total-tau and phosphorylated-tau levels (cross-sectionally); and hippocampal volume, fluorodeoxyglucose positron emission tomography results and Alzheimer's Disease Assessment Scale-cognitive subscale scores (longitudinally). Cerebrospinal fluid and positron emission tomography amyloid-β were highly correlated, but adjusting one of these predictors for the other revealed that they both provided partially independent information when predicting diagnosis, APOE ε4, hippocampal volume, metabolism, cognition, total-tau and phosphorylated-tau (the 95% confidence intervals of the adjusted effects did not include zero). Cerebrospinal fluid amyloid-β was more strongly related to APOE ε4 whereas positron emission tomography amyloid-β was more strongly related to tau levels (P < 0.05). Discordance (mainly isolated cerebrospinal fluid amyloid-β positivity) differed by diagnostic group (P < 0.001) and was seen in 21% of cognitively healthy people but only 6% in dementia patients. The finding that

  8. Independent information from cerebrospinal fluid amyloid-β and florbetapir imaging in Alzheimer's disease

    PubMed Central

    Insel, Philip S.; Donohue, Michael; Landau, Susan; Jagust, William J.; Shaw, Leslie M.; Trojanowski, John Q.; Zetterberg, Henrik; Blennow, Kaj; Weiner, Michael W.

    2015-01-01

    Reduced cerebrospinal fluid amyloid-β42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree and may represent partly different aspects of the underlying Alzheimer's disease pathology. The goal of this study was therefore to test if cerebrospinal fluid and positron emission tomography amyloid-β biomarkers are independently related to other Alzheimer's disease markers, and to examine individuals who are discordantly classified by these two biomarker modalities. Cerebrospinal fluid and positron emission tomography amyloid-β were measured at baseline in 769 persons [161 healthy controls, 68 subjective memory complaints, 419 mild cognitive impairment and 121 Alzheimer's disease dementia, mean age 72 years (standard deviation 7 years), 47% females] and used to predict diagnosis, APOE ε4 carriage status, cerebral blood flow, cerebrospinal fluid total-tau and phosphorylated-tau levels (cross-sectionally); and hippocampal volume, fluorodeoxyglucose positron emission tomography results and Alzheimer's Disease Assessment Scale-cognitive subscale scores (longitudinally). Cerebrospinal fluid and positron emission tomography amyloid-β were highly correlated, but adjusting one of these predictors for the other revealed that they both provided partially independent information when predicting diagnosis, APOE ε4, hippocampal volume, metabolism, cognition, total-tau and phosphorylated-tau (the 95% confidence intervals of the adjusted effects did not include zero). Cerebrospinal fluid amyloid-β was more strongly related to APOE ε4 whereas positron emission tomography amyloid-β was more strongly related to tau levels (P < 0.05). Discordance (mainly isolated cerebrospinal fluid amyloid-β positivity) differed by diagnostic group (P < 0.001) and was seen in 21% of cognitively healthy people but only 6% in dementia patients. The finding that

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

    PubMed

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

    2016-02-01

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

  10. How appropriate are cerebrospinal fluid polymerase chain reaction requests for suspected central nervous system infections?

    PubMed

    Mamoojee, Yaasir; Chadwick, David

    2011-12-01

    Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) assays have become the main diagnostic tests for central nervous system viral infections in recent years. Previous studies have suggested algorithms based on CSF leukocyte count and total protein levels to determine when CSF PCR assays are indicated. Based on these criteria, 1,469 CSF PCR tests requested over a two-year period were reviewed. A proportion of positive PCR results were found in children with normal CSF, unlike in adults where such occurrences were extremely rare. The results suggest that applying a strategy of screening CSF specimens using leukocyte count, glucose and protein, at least in adults, may have avoided more than half of CSF PCR requests with little detriment to patient care and considerable cost savings. Larger prospective studies are needed to determine whether algorithms using standard CSF parameters and clinical information can optimise the use of CSF PCR assays in clinical practice. PMID:22268308

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

    SciTech Connect

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

    1982-11-01

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

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

    SciTech Connect

    Halperin, J.A.; Martin, A.M.; Malave, S.

    1985-08-12

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

  13. Proteome analysis of biomarkers in the cerebrospinal fluid of neuromyelitis optica patients

    PubMed Central

    Bai, Shumei; Guo, Xuxiao; Qin, Zhaoyu; Wang, Banqin; Li, Xiaohong; Qin, Yanjiang; Liu, Yi-Hsin

    2009-01-01

    Purpose To better understand the pathophysiological mechanisms underlying neuromyelitis optica (NMO), we developed a proteomics platform for biomarker discovery in the cerebrospinal fluid (CSF) of patients with NMO. Methods Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) were used to compare the CSF proteome of NMO patients with that of controls. A subsequent ELISA and western blot analysis were performed to verify the results of the proteomic analysis. Pathway Studio 5.0 software was used to determine possible functional interactions among these differentially expressed proteins. Results Using 2-DE and MALDI-TOF MS, we identified 11 differentially expressed proteins and two isoforms of these same proteins. The expression of four proteins was enhanced, whereas the expression of seven proteins was reduced in the NMO group in comparison to the control group. These differences in protein expression were confirmed by performing ELISA and western blot analyses (p<0.01). Protein network analyses revealed biologic interactions and cross-talks among these differentially expressed proteins. Conclusions Because of their unique expression profile in NMO CSFs, these proteins are candidate biomarkers for NMO. Thus, our findings may have important implications for both the diagnosis of NMO and the further understanding of its pathogenesis. PMID:19710940

  14. Proteomic analysis of cerebrospinal fluid for relapsing-remitting multiple sclerosis and clinically isolated syndrome

    PubMed Central

    PAVELEK, ZBYŠEK; VYŠATA, OLDŘICH; TAMBOR, VOJTĚCH; PIMKOVÁ, KRISTÝNA; VU, DAI LONG; KUČA, KAMIL; ŠŤOURAČ, PAVEL; VALIŠ, MARTIN

    2016-01-01

    Early diagnosis and treatment of multiple sclerosis (MS) in the initial stages of the disease can significantly retard its progression. The aim of the present study was to identify changes in the cerebrospinal fluid proteome in patients with relapsing-remitting MS and clinically isolated MS syndrome who are at high risk of developing MS (case group) compared to healthy population (control) in order to identify potential new markers, which could ultimately aid in early diagnosis of MS. The protein concentrations of each of the 11 case and 15 control samples were determined using a bicinchoninic acid assay. Nanoscale liquid chromatography coupled with tandem mass spectrometry was used for protein identification. Proteomics data were processed using the Perseus software suite and R. The results were filtered using the Benjamini-Hochberg procedure for the false discovery rate (FDR) correction (FDR<0.05). The results showed that, 26 proteins were significantly dysregulated in case samples compared to the controls. Nine proteins were found to be significantly less abundant in case samples, while the abundance of 17 proteins was significantly increased in case samples compared to controls. Three of the proteins were previously linked to RR MS, including immunoglobulin (Ig) γ-1 chain C region, Ig heavy chain V–III region BRO and Ig κ chain C region. Three proteins that were uniquely expressed in patients with RR MS were identified and these proteins may serve as prognostic biomarkers for identifying patients with a high risk of developing RR MS. PMID:27347402

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

    PubMed Central

    FARIVAR, Shirin; MOHAMADZADE, Zahra; SHIARI, Reza; FAHIMZAD, Alireza

    2015-01-01

    Objective Wharton’s jelly (WJ) is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF) on neural differentiation of human WJ stem cells. Material & Methods The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2), and Glial Fibrillary Astrocytic Protein (GFAP) for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR). Results Treatment with 100 and 200μg/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer. Conclusion RT-PCR showed that cerebrospinal fluid promotes the expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially at a concentration of 200 μl/ml. In summary, CSF induces neurogenesis of WJ stem cells that encourages tissue engineering

  16. One-time intrathecal triamcinolone acetonide application alters the redox potential in cerebrospinal fluid of progressive multiple sclerosis patients: a pilot study

    PubMed Central

    Müller, Thomas; Herrling, Thomas; Lütge, Sven; Lohse, Lutz; Öhm, Gabi; Jung, Katinka

    2016-01-01

    Introduction: Cerebrospinal fluid analysis may provide insight into the interplay between chronic inflammation and response to treatment. Objectives: To demonstrate the impact of one intrathecal triamcinolone injection on the redox potential and on ascorbyl radical appearance in the cerebrospinal fluid of chronic progressive multiple sclerosis patients. Methods: A total of 16 patients received 40 mg triamcinolone. Electron-spin resonance spectroscopy measured the oxidation range after copper ion [Cu (II)] addition and ascorbyl-radical bioavailability. Results: There was an increase of Cu (II) ion absorption, which reflects an augmented content of reduced proteins. Ascorbyl radicals were present in contrast to healthy controls according to the literature. Conclusion: Intrathecal steroid application alters the redox potential in cerebrospinal fluid. Our findings support the beneficial role of steroids on oxidative stress generally demonstrated by ascorbyl radical appearance. Reactive oxygen species decline is necessary for an upregulated production of reduced proteins. PMID:27366232

  17. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

    PubMed Central

    Ayton, Scott; Faux, Noel G.; Bush, Ashley I.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack Jr., Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Marcel Mesulam, M.; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Leon; Buckholtz, Neil; Albert, Marylyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino II, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Saleem Ismail, M.; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristine; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Elizabeth Smith, Karen; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Ashok Raj, Balebail; Neylan, Thomas; Grafman, Jordan; Davis, Melissa; Morrison, Rosemary; Hayes, Jacqueline; Finley, Shannon; Friedl, Karl; Fleischman, Debra; Arfanakis, Konstantinos; James, Olga; Massoglia, Dino; Jay Fruehling, J.; Harding, Sandra; Peskind, Elaine R.; Petrie, Eric C.; Li, Gail; Yesavage, Jerome A.; Taylor, Joy L.; Furst, Ansgar J.

    2015-01-01

    Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD. PMID:25988319

  18. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE.

    PubMed

    Ayton, Scott; Faux, Noel G; Bush, Ashley I

    2015-01-01

    Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD. PMID:25988319

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

    PubMed

    Reiber, Hansotto

    2016-06-01

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

  20. Clearance of macromolecular and particulate substances from the cerebrospinal fluid system of the rat.

    PubMed

    Mann, J D; Butler, A B; Johnson, R N; Bass, N H

    1979-03-01

    Arachnoid villi in the intracranial dural sinuses constitute the principal sites for absorption of proteins and particulates from the cerebrospinal fluid (CSF) system. Although arachnoid villi in the rat are morphologically less complex than those found in other mammals, their resistance to CSF outflow, as assessed by a graded series of contstant flow manometric infusions, is similar to that found in other species. Moreover, inulin and polystyrene beads, when infused into the spinal subarachnoid space of rats, are rapidly cleared from the CSF system into intracranial dural sinuses. Inulin appeared in sinus blood 3 minutes after onset of infusion and reached concentrations 26 times greater than those found in the systemic circulation; particulate matter in the form of 0.5 micrometer polystyrene beads showed similar efflux characteristics. Hence, the CSF system of the rat is functionally similar to that found in other mammalian species, with arachnoid villi constituting a major efflux route for clearance of macromolecular and particulate substances. PMID:422986

  1. Methods for the Specific Detection and Quantitation of Amyloid-β Oligomers in Cerebrospinal Fluid.

    PubMed

    Schuster, Judith; Funke, Susanne Aileen

    2016-05-01

    Protein misfolding and aggregation are fundamental features of the majority of neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia, and prion diseases. Proteinaceous deposits in the brain of the patient, e.g., amyloid plaques consisting of the amyloid-β (Aβ) peptide and tangles composed of tau protein, are the hallmarks of AD. Soluble oligomers of Aβ and tau play a fundamental role in disease progression, and specific detection and quantification of the respective oligomeric proteins in cerebrospinal fluid may provide presymptomatically detectable biomarkers, paving the way for early diagnosis or even prognosis. Several studies on the development of techniques for the specific detection of Aβ oligomers were published, but some of the existing tools do not yet seem to be satisfactory, and the study results are contradicting. The detection of oligomers is challenging due to their polymorphous and unstable nature, their low concentration, and the presence of competing proteins and Aβ monomers in body fluids. Here, we present an overview of the current state of the development of methods for Aβ oligomer specific detection and quantitation. The methods are divided in the three subgroups: (i) enzyme linked immunosorbent assays (ELISA), (ii) methods for single oligomer detection, and (iii) others, which are mainly biosensor based methods. PMID:27163804

  2. Penetration of aztreonam into cerebrospinal fluid of patients with bacterial meningitis.

    PubMed Central

    Modai, J; Vittecoq, D; Decazes, J M; Wolff, M; Meulemans, A

    1986-01-01

    The penetration of aztreonam into the cerebrospinal fluid was determined in 16 patients with bacterial meningitis undergoing treatment with other antibiotics. Three aztreonam doses of 30 mg/kg were infused intravenously over 30 to 45 min at 8-h intervals, first between days 2 and 4 and again between days 11 and 20 after onset of the disease. Concentrations of aztreonam in serum and cerebrospinal fluid samples obtained at 60, 90, 120, and 240 min after the third aztreonam dose were measured by high-pressure liquid chromatography. The concentrations of aztreonam in cerebrospinal fluid ranged from 3.5 to 62 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. These concentrations were equal to or higher than the MICs for most of the gram-negative bacilli (including Pseudomonas aeruginosa). PMID:3717933

  3. Antibodies Against Equine Herpesvirus 1 in the Cerebrospinal Fluid in the Horse

    PubMed Central

    Blythe, Linda L.; Mattson, Donald E.; Lassen, E. Duane; Craig, A. Morrie

    1985-01-01

    Neutralizing antibodies against equine herpesvirus 1 were measured in serum and cerebrospinal fluid of 16 horses and ponies from a closed herd both before and after vaccination with modified live equine herpesvirus 1. These titers were also measured in 22 neurologically normal and 15 neurologically abnormal horses at a teaching hospital. Animals from the closed herd had prevaccination serum titers up to 1:8 and postvaccination serum titers up to 1:128. Horses from the teaching hospital had serum titers up to 1:64. Cerebrospinal fluid titers were not detected in the vaccinated horses or the neurologically normal horses but a low titer (1:8) was noted in one neurologically abnormal horse. This titer probably resulted from hemorrhage into the cerebrospinal fluid following trauma. PMID:17422553

  4. A corny cause of cerebrospinal fluid ascites: A case report and review of literature

    PubMed Central

    Jamal, Hira; Abrams, Gary

    2016-01-01

    Objective: To report a rare cause of cerebrospinal fluid ascites. Methods: A 37-year-old female with history of intracranial hypertension and a ventriculo-peritoneal shunt was referred to liver clinic for evaluation of newly developed ascites. Results: Initially, the cause of ascites was thought to be secondary to a liver etiology. However, this was excluded after a comprehensive evaluation including portal pressure measurements. We determined the ascites to be infected cerebrospinal fluid secondary to a rare commensal organism, Corynebacterium non-Jeikeium, which resolved after removing ventriculo-peritoneal shunt, appropriate antibiotics and conversion to a ventriculo-atrial shunt. Conclusion: Cerebrospinal fluid ascites is a rare complication of VP shunts and since 1976 only 8 cases of Corynebacterium non jk VP shunt infections have been reported in the literature but none associated with ascites. Also this report highlights the beneficial role of transjugular portal pressure measurements in the evaluation of ascites. PMID:27489721

  5. Proteomic Analysis of Cerebrospinal Fluid in Pneumococcal Meningitis Reveals Potential Biomarkers Associated with Survival

    PubMed Central

    Goonetilleke, Upali R.; Scarborough, Matthew; Ward, Stephen A.; Gordon, Stephen B.

    2016-01-01

    Background Patients with pneumococcal meningitis often die or have severe neurological damage despite optimal antibiotic therapy. New or improved therapy is required. The delivery of new interventions will require an improved understanding of the disease pathogenesis. Our objective was to learn more about the pathophysiology of severe meningitis through the interpretation of differences in the proteomic profile of cerebrospinal fluid (CSF) from patients with meningitis. Methods Two-dimensional polyacrylamide gel electrophoresis of CSF from normal subjects (controls, n = 10) and patients with pneumococcal meningitis (n = 20) was analyzed. Spot differences were compared and identified between controls, nonsurvivors (n = 9), and survivors (n = 11). Results Protein concentration in CSF of patients with meningitis was 4-fold higher than in CSF of control subjects (7.0 mg/mL vs 0.23 mg/mL; P < .01). A mean of 2466 discrete protein spots was present in CSF of patients with meningitis. Thirty-four protein spots were differentially expressed in CSF of nonsurvivors, compared with survivors. None of these protein spots were observed in CSF of control subjects. Conclusions Proteomic screening of CSF yields potential biomarkers capable of differentiating control subjects from nonsurvivors and survivors of meningitis. Proteins involved in the inflammatory process and central metabolism were represented in the differentially expressed protein repertoire. PMID:20608875

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

    PubMed Central

    Mattsson, Niklas

    2016-01-01

    See Rabinovici (doi:10.1093/brain/aww025) for a scientific commentary on this article. Cerebral accumulation of amyloid-β is thought to be the starting mechanism in Alzheimer’s disease. Amyloid-β can be detected by analysis of cerebrospinal fluid amyloid-β42 or amyloid positron emission tomography, but it is unknown if any of the methods can identify an abnormal amyloid accumulation prior to the other. Our aim was to determine whether cerebrospinal fluid amyloid-β42 change before amyloid PET during preclinical stages of Alzheimer’s disease. We included 437 non-demented subjects from the prospective, longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. All underwent 18F-florbetapir positron emission tomography and cerebrospinal fluid amyloid-β42 analysis at baseline and at least one additional positron emission tomography after a mean follow-up of 2.1 years (range 1.1–4.4 years). Group classifications were based on normal and abnormal cerebrospinal fluid and positron emission tomography results at baseline. We found that cases with isolated abnormal cerebrospinal fluid amyloid-β and normal positron emission tomography at baseline accumulated amyloid with a mean rate of 1.2%/year, which was similar to the rate in cases with both abnormal cerebrospinal fluid and positron emission tomography (1.2%/year, P = 0.86). The mean accumulation rate of those with isolated abnormal cerebrospinal fluid was more than three times that of those with both normal cerebrospinal fluid and positron emission tomography (0.35%/year, P = 0.018). The group differences were similar when analysing yearly change in standardized uptake value ratio of florbetapir instead of percentage change. Those with both abnormal cerebrospinal fluid and positron emission tomography deteriorated more in memory and hippocampal volume compared with the other groups (P < 0.001), indicating that they were closer to Alzheimer’s disease dementia. The results were replicated after

  7. Human African trypanosomiasis: a latex agglutination field test for quantifying IgM in cerebrospinal fluid.

    PubMed Central

    Lejon, V.; Büscher, P.; Sema, N. H.; Magnus, E.; Van Meirvenne, N.

    1998-01-01

    LATEX/IgM, a rapid agglutination test for the semi-quantitative detection of IgM in cerebrospinal fluid of patients with African trypanosomiasis, is described in this article. The lyophilized reagent has been designed for field use and remains stable at 45 degrees C for one year. The test has been evaluated on cerebrospinal fluid samples from trypanosome-infected and non-infected patients, by comparison with commercial latex agglutination, radial immunodiffusion, and nephelometry. All test systems yielded similar results. PMID:10191550

  8. Severe dehydration and acute renal failure associated with external ventricular drainage of cerebrospinal fluid in children.

    PubMed

    Simpson, S; Yung, M; Slater, A

    2006-10-01

    We report three paediatric cases of severe dehydration and hyponatraemia with circulatory compromise associated with the use of external ventricular drainage of cerebrospinal fluid. Two of the children had cardiac arrests. All were successfully resuscitated. While there were additional factors that contributed to other fluid losses, and fluid balance data are incomplete, these cases highlight a need for increased vigilance when managing children with external ventricular drains. PMID:17061645

  9. Cerebrospinal Fluid from Sporadic Amyotrophic Lateral Sclerosis Patients Induces Mitochondrial and Lysosomal Dysfunction.

    PubMed

    Sharma, Aparna; Varghese, Anu Mary; Vijaylakshmi, Kalyan; Sumitha, Rajendrarao; Prasanna, V K; Shruthi, S; Chandrasekhar Sagar, B K; Datta, Keshava K; Gowda, Harsha; Nalini, Atchayaram; Alladi, Phalguni Anand; Christopher, Rita; Sathyaprabha, Talakad N; Raju, Trichur R; Srinivas Bharath, M M

    2016-05-01

    In our laboratory, we have developed (1) an in vitro model of sporadic Amyotrophic Lateral Sclerosis (sALS) involving exposure of motor neurons to cerebrospinal fluid (CSF) from sALS patients and (2) an in vivo model involving intrathecal injection of sALS-CSF into rat pups. In the current study, we observed that spinal cord extract from the in vivo sALS model displayed elevated reactive oxygen species (ROS) and mitochondrial dysfunction. Quantitative proteomic analysis of sub-cellular fractions from spinal cord of the in vivo sALS model revealed down-regulation of 35 mitochondrial proteins and 4 lysosomal proteins. Many of the down-regulated mitochondrial proteins contribute to alterations in respiratory chain complexes and organellar morphology. Down-regulated lysosomal proteins Hexosaminidase, Sialidase and Aryl sulfatase also displayed lowered enzyme activity, thus validating the mass spectrometry data. Proteomic analysis and validation by western blot indicated that sALS-CSF induced the over-expression of the pro-apoptotic mitochondrial protein BNIP3L. In the in vitro model, sALS-CSF induced neurotoxicity and elevated ROS, while it lowered the mitochondrial membrane potential in rat spinal cord mitochondria in the in vivo model. Ultra structural alterations were evident in mitochondria of cultured motor neurons exposed to ALS-CSF. These observations indicate the first line evidence that sALS-CSF mediated mitochondrial and lysosomal defects collectively contribute to the pathogenesis underlying sALS. PMID:26646005

  10. Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid.

    PubMed

    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

    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

  11. Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice

    PubMed Central

    Bjorefeldt, Andreas; Andreasson, Ulf; Daborg, Jonny; Riebe, Ilse; Wasling, Pontus; Zetterberg, Henrik; Hanse, Eric

    2015-01-01

    The composition of brain extracellular fluid is shaped by a continuous exchange of substances between the cerebrospinal fluid (CSF) and interstitial fluid. The CSF is known to contain a wide range of endogenous neuromodulatory substances, but their collective influence on neuronal activity has been poorly investigated. We show here that replacing artificial CSF (aCSF), routinely used for perfusion of brain slices in vitro, with human CSF (hCSF) powerfully boosts spontaneous firing of CA1, CA3 and layer 5 pyramidal neurons in the rat brain slice. CA1 pyramidal neurons in hCSF display lowered firing thresholds, more depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The increased excitability of CA1 pyramidal neurons was completely occluded by intracellular application of GTPγS, suggesting that endogenous neuromodulators in hCSF act on G-protein coupled receptors to enhance excitability. We found no increase in spontaneous inhibitory synaptic transmission by hCSF, indicating a differential effect on glutamatergic and GABAergic neurons. Our findings highlight a previously unknown function of the CSF in promoting spontaneous excitatory activity, and may help to explain differences observed in the activity of pyramidal neurons recorded in vivo and in vitro. PMID:25556798

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

    PubMed

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

    2016-09-01

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

  13. Comparative proteomic profiling of cerebrospinal fluid between living and post mortem ALS and control subjects

    PubMed Central

    RANGANATHAN, SRIKANTH; NICHOLL, GEORGINA C.B.; HENRY, SARAH; LUTKA, FRAN; SATHANOORI, RAMASRI; LACOMIS, DAVID; BOWSER, ROBERT

    2010-01-01

    Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), lack definitive diagnostic tests or biomarkers of disease progression. Most studies that investigate protein abnormalities in ALS have used biofluids such as blood or cerebrospinal fluid (CSF), while some have used post mortem tissue or CSF samples. Since ALS disease progression and post mortem effects probably induce significant alterations to protein modifications or proteolysis, we directly examined the CSF proteome from ALS subjects at various lengths of time from symptom onset and at autopsy by mass spectrometry based proteomics. CSF was also obtained from both healthy age-matched control subjects and at autopsy from healthy and Alzheimer's disease (AD) controls. We identified significant differences in the CSF proteome between living and post mortem ALS subjects, as well as living and post mortem control subjects. We also noted differences in the CSF proteome of ALS subjects that have exhibited symptoms for varying lengths of time and between ALS and AD subjects at end-stage of disease. This is the first study describing differences in the CSF proteome from post mortem and living ALS subjects using a mass spectrometric approach. These differences highlight the importance of utilizing CSF from living ALS subjects near the time of symptom onset for the identification of early protein biomarkers, although some protein alterations that occur early in the disease process are maintained throughout the course of disease and in post mortem samples. PMID:17852009

  14. Letter to the editor: Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent report (Formisano et al., 2013) identified clinical sacrocystosis in 2 adult sheep. The diagnosis relied primarily on characterization of DNA extracted from cerebrospinal fluid (CSF) and paraffin-embedded heart tissue. Parasites identified as merozoites were identified in CSF smears stained...

  15. Extensive Recruitment of Plasma Blasts to the Cerebrospinal Fluid in Toscana Virus Encephalitis

    PubMed Central

    Schirmer, Lucas; Wölfel, Silke; Georgi, Enrico; Ploner, Markus; Bauer, Barbara; Hemmer, Bernhard

    2015-01-01

    An unexpectedly extensive recruitment of B cells and plasma blasts to the cerebrospinal fluid (CSF) in a patient with Toscana virus (TOSV) encephalitis is described. Acute infection by TOSV was demonstrated by serological methods and by detection of TOSV-specific nucleic acid in the CSF by real-time polymerase chain reaction and sequencing. PMID:26393235

  16. Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis

    PubMed Central

    Graham, Lisa M.; Schutz, Charlotte; Scriba, Thomas J.; Wilkinson, Robert J.; Boulware, David R.; Meintjes, Graeme; Lalloo, David G.; Urban, Britta C.

    2015-01-01

    Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical decision making is hampered by the time involved to perform quantitative cultures. Here, we demonstrate the potential of flow cytometry as a novel and rapid technique to address this issue. PMID:26719441

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

    PubMed

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

    2012-06-01

    Central catecholamine deficiency characterizes α-synucleinopathies such as Parkinson's disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson's disease and two other 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 < 0.0001; P < 0.0001; P = 0.0002). Dihydroxyphenylglycol was also lower in the three synucleinopathies (8.82 ± 0.44, 7.75 ± 0.42, 5.82 ± 0.65 nmol/l) than controls (11.0 ± 0.62 nmol/l; P = 0.009, P < 0.0001, P < 0.0001). Dihydroxyphenylacetic acid was lower and dihydroxyphenylglycol higher in Parkinson's disease than in pure autonomic failure. Dihydroxyphenylacetic acid was 100% sensitive at 89% specificity in separating patients with recent onset of parkinsonism from controls but was of no value in differentiating Parkinson's disease from multiple system atrophy. Synucleinopathies feature 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

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

    PubMed

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

    2016-07-15

    Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016. PMID:27245177

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

    PubMed Central

    MATSUMAE, Mitsunori; SATO, Osamu; HIRAYAMA, Akihiro; HAYASHI, Naokazu; TAKIZAWA, Ken; ATSUMI, Hideki; SORIMACHI, Takatoshi

    2016-01-01

    Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016. PMID:27245177

  20. Interactions between Flow Oscillations and Biochemical Parameters in the Cerebrospinal Fluid

    PubMed Central

    Puy, Vincent; Zmudka-Attier, Jadwiga; Capel, Cyrille; Bouzerar, Roger; Serot, Jean-Marie; Bourgeois, Anne-Marie; Ausseil, Jérome; Balédent, Olivier

    2016-01-01

    The equilibrium between the ventricular and lumbar cerebrospinal fluid (CSF) compartments may be disturbed (in terms of flow and biochemistry) in patients with chronic hydrocephalus (CH). Using flow magnetic resonance imaging (MRI) and CSF assays, we sought to determine whether changes in CSF were associated with biochemical alterations. Nine elderly patients with CH underwent phase-contrast MRI. An index of CSF dynamics (Idyn) was defined as the product of the lumbar and ventricular CSF flows. During surgery, samples of CSF were collected from the lumbar and ventricular compartments and assayed for chloride, glucose and total protein. The lumbar/ventricular (L/V) ratio was calculated for each analyte. The ratio between measured and expected levels (Ibioch) was calculated for each analyte and compared with Idyn. Idyn varied from 0 to 100.103μl2.s2. In contrast to the L/V ratios for chloride and glucose, the L/V ratio for total protein varied markedly from one patient to another (mean ± standard deviation (SD): 2.63 ± 1.24). The Ibioch for total protein was strongly correlated with the corresponding Idyn (Spearman’s R: 0.98; p < 5 × 10−5).We observed correlated alterations in CSF flow and biochemical parameters in patients with CH. Our findings also highlight the value of dynamic flow analysis in the interpretation of data on CSF biochemistry. PMID:27445797

  1. Interactions between Flow Oscillations and Biochemical Parameters in the Cerebrospinal Fluid.

    PubMed

    Puy, Vincent; Zmudka-Attier, Jadwiga; Capel, Cyrille; Bouzerar, Roger; Serot, Jean-Marie; Bourgeois, Anne-Marie; Ausseil, Jérome; Balédent, Olivier

    2016-01-01

    The equilibrium between the ventricular and lumbar cerebrospinal fluid (CSF) compartments may be disturbed (in terms of flow and biochemistry) in patients with chronic hydrocephalus (CH). Using flow magnetic resonance imaging (MRI) and CSF assays, we sought to determine whether changes in CSF were associated with biochemical alterations. Nine elderly patients with CH underwent phase-contrast MRI. An index of CSF dynamics (Idyn) was defined as the product of the lumbar and ventricular CSF flows. During surgery, samples of CSF were collected from the lumbar and ventricular compartments and assayed for chloride, glucose and total protein. The lumbar/ventricular (L/V) ratio was calculated for each analyte. The ratio between measured and expected levels (Ibioch) was calculated for each analyte and compared with Idyn. Idyn varied from 0 to 100.10(3)μl(2).s(2). In contrast to the L/V ratios for chloride and glucose, the L/V ratio for total protein varied markedly from one patient to another (mean ± standard deviation (SD): 2.63 ± 1.24). The Ibioch for total protein was strongly correlated with the corresponding Idyn (Spearman's R: 0.98; p < 5 × 10(-5)).We observed correlated alterations in CSF flow and biochemical parameters in patients with CH. Our findings also highlight the value of dynamic flow analysis in the interpretation of data on CSF biochemistry. PMID:27445797

  2. High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.

    PubMed

    Pleticha, J; Malkmus, S A; Heilmann, L F; Veesart, S L; Rezek, R; Xu, Q; Yaksh, T L; Beutler, A S

    2015-02-01

    Intrathecal (IT) gene transfer using adeno-associated virus (AAV) may be clinically promising as a treatment for chronic pain if it can produce sufficiently high levels of a transgene product in the cerebrospinal fluid (CSF). Although this strategy was developed in rodents, no studies investigating CSF levels of an analgesic or antiallodynic protein delivered by IT AAV have been performed in large animals. Interleukin-10 (IL-10) is an antiallodynic cytokine for which target therapeutic levels have been established in rats. The present study tested IT AAV8 encoding either human IL-10 (hIL-10) or enhanced green fluorescent protein (EGFP) in a dog model of IT drug delivery. AAV8/hIL-10 at a dose of 3.5 × 10(12) genome copies induced high hIL-10 levels in the CSF, exceeding the target concentration previously found to be antiallodynic in rodents by >1000-fold. AAV8/EGFP targeted the primary sensory and motor neurons and the meninges. hIL-10, a xenogeneic protein in dogs, induced anti-hIL-10 antibodies detectable in the CSF and serum of dogs. The high hIL-10 levels demonstrate the efficacy of AAV for delivery of secreted transgenes into the IT space of large animals, suggesting a strong case for further development toward clinical testing. PMID:25354684

  3. Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway.

    PubMed

    Chang, Jessica T; Lehtinen, Maria K; Sive, Hazel

    2016-01-01

    Cerebrospinal fluid (CSF) includes conserved factors whose function is largely unexplored. To assess the role of CSF during embryonic development, CSF was repeatedly drained from embryonic zebrafish brain ventricles soon after their inflation. Removal of CSF increased cell death in the diencephalon, indicating a survival function. Factors within the CSF are required for neuroepithelial cell survival as injected mouse CSF but not artificial CSF could prevent cell death after CSF depletion. Mass spectrometry analysis of the CSF identified retinol binding protein 4 (Rbp4), which transports retinol, the precursor to retinoic acid (RA). Consistent with a role for Rbp4 in cell survival, inhibition of Rbp4 or RA synthesis increased neuroepithelial cell death. Conversely, ventricle injection of exogenous human RBP4 plus retinol, or RA alone prevented cell death after CSF depletion. Zebrafish rbp4 is highly expressed in the yolk syncytial layer, suggesting Rbp4 protein and retinol/RA precursors can be transported into the CSF from the yolk. In accord with this suggestion, injection of human RBP4 protein into the yolk prevents neuroepithelial cell death in rbp4 loss-of-function embryos. Together, these data support the model that Rbp4 and RA precursors are present within the CSF and used for synthesis of RA, which promotes embryonic neuroepithelial survival. PMID:25980532

  4. Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis

    PubMed Central

    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

    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. PMID:16313519

  5. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

    PubMed

    Doronin, Vasilii B; Parkhomenko, Taisiya A; Castellazzi, Massimiliano; Cesnik, Edward; Buneva, Valentina N; Granieri, Enrico; Nevinsky, Georgy A

    2016-01-01

    We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed. PMID:27196086

  6. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

    PubMed Central

    Doronin, Vasilii B.; Parkhomenko, Taisiya A.; Castellazzi, Massimiliano; Cesnik, Edward; Buneva, Valentina N.; Granieri, Enrico; Nevinsky, Georgy A.

    2016-01-01

    We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed. PMID:27196086

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

    PubMed

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

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p < 0.001), MV (p = 0.004), and VV (p = 0.001) genotype. Receiver operating characteristic analyses showed values of area under the curve of 0.76-0.80 for the different genotypes indicating a good diagnostic validity of the test. Total tau can be used as a diagnostic test for the assessment of prion protein type when codon 129 genotype is known. It provides valuable information for physicians and next of kin about the further course of disease. PMID:25749129

  8. Proteomic Identification of Biomarkers in the Cerebrospinal fluid (CSF) of Astrocytoma Patients

    PubMed Central

    Khwaja, Fatima W.; Reed, Matthew S.; Olson, Jeffrey J.; Schmotzer, Brian J.; Gillespie, G.Yancey; Guha, Abhijit; Groves, Morris D.; Kesari, Santosh; Pohl, Jan; Van Meir, Erwin G.

    2008-01-01

    The monitoring of changes in the protein composition of the cerebrospinal fluid (CSF) can be used as a sensitive indicator of central nervous system (CNS) pathology, yet its systematic application to analysis of CNS neoplasia has been limited. There is a pressing need for both a better understanding of gliomagenesis, and the development of reliable biomarkers of the disease. In this report, we used two proteomic techniques, two-dimensional gel electrophoresis (2-DE) and cleavable Isotope-Coded Affinity Tag (cICAT), to compare CSF proteomes in order to identify tumor and grade specific biomarkers in patients bearing brain tumors of differing histologies and grades. Retrospective analyses were performed on 60 samples derived from astrocytomas WHO grade II, III and IV, schwannomas, metastastic brain tumors, inflammatory samples and non-neoplastic controls. We identified 103 potential tumor-specific markers; of which 20 were high-grade astrocytoma-specific. These investigations allowed us to identify a spectrum of signature proteins that could differentiate between low (AII) and high-grade (AIV) astrocytoma, which may represent new diagnostic, prognostic and disease follow-up markers when used alone or in combination. These candidate biomarkers may also have functional properties that play a critical role in the development and malignant progression of human astrocytomas, thus possibly representing novel therapeutic targets for this highly lethal disease. PMID:17269713

  9. Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer's disease patients.

    PubMed

    Capo, Concetta R; Arciello, Mario; Squitti, Rosanna; Cassetta, Emanuele; Rossini, Paolo Maria; Calabrese, Lilia; Rossi, Luisa

    2008-06-01

    The level of the apo-form of the copper enzyme ceruloplasmin (CP) is an established peripheral marker in diseases associated with copper imbalance. In view of the proposal that disturbances of copper homeostasis may contribute to neurodegeneration associated with Alzheimer's disease (AD), the present work investigates, by Western blot and non-reducing SDS-PAGE followed by activity staining, the features of CP protein, and the copper/CP relationship in cerebrospinal fluid (CSF) and serum of AD patients. Results show that only a fraction of total copper is associated with CP in the CSF, at variance with serum, both in affected and in healthy individuals. Furthermore, a conspicuous amount of apo-ceruloplasmin and a decrease of CP oxidase activity characterize the CSF of the affected individuals, and confirm that an impairment of copper metabolism occurs in their central nervous system. In the CSF of AD patients the decrease of active CP, associated with the increase in the pool of copper not sequestered by this protein, may play a role in the neurodegenerative process. PMID:18060472

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

    PubMed Central

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

    2013-01-01

    Accurate ante mortem diagnosis in frontotemporal lobar degeneration (FTLD) is crucial to the development and implementation of etiology-based therapies. Several neurodegenerative disease-associated proteins, including the major protein constituents of inclusions in Alzheimer's disease (AD) associated with amyloid-beta (Aβ1−42) plaque and tau neurofibrillary tangle pathology, can be measured in cerebrospinal fluid (CSF) for diagnostic applications. Comparative studies using autopsy-confirmed samples suggest that CSF total-tau (t-tau) and Aβ1−42 levels can accurately distinguish FTLD from AD, with a high t-tau to Aβ1−42 ratio diagnostic of AD; however, there is also an urgent need for FTLD-specific biomarkers. These analytes will require validation in large autopsy-confirmed cohorts and face challenges of standardization of within- and between-laboratory sources of error. In addition, CSF biomarkers with prognostic utility and longitudinal study of CSF biomarker levels over the course of disease are also needed. Current goals in the field include identification of analytes that are easily and reliably measured and can be used alone or in a multi-modal approach to provide an accurate prediction of underlying neuropathology for use in clinical trials of disease modifying treatments in FTLD. To achieve these goals it will be of the utmost importance to view neurodegenerative disease, including FTLD, as a clinicopathological entity, rather than exclusively a clinical syndrome. PMID:23440936

  11. Cerebrospinal Fluid-Cutaneous Fistula After Continuous Spinal Catheter in an Obstetric Patient.

    PubMed

    Lenart, Mark J; Carness, Jeffrey M

    2016-09-01

    A 23-year-old woman at 41 weeks and 6 days estimated gestational age underwent continuous spinal analgesia for labor after a recognized, unintended dural puncture. Excellent analgesia was maintained throughout labor and vaginal delivery, the intrathecal catheter was left in situ for 24 hours postpartum, and the catheter was subsequently removed without apparent complication. On physical examination during her anesthesia postoperative visit, clear fluid was noted to be slowly draining from the catheter insertion site. Although she denied all symptoms associated with a dural puncture, including headache, a cerebrospinal fluid-cutaneous fistula was diagnosed. An epidural blood patch was placed, which terminated the cerebrospinal fluid leak. No long-term complications were evident. Subsequent literature review revealed a rare incidence of this type of complication and varied recommendations for intervention and optimal management. We review the literature with regard to this complication and offer discussion regarding the various suggested means of diagnosis and therapy. PMID:27580408

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

    PubMed

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

    2005-05-01

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

  13. The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

    PubMed

    Dowling, N Maritza; Johnson, Sterling C; Gleason, Carey E; Jagust, William J

    2015-01-15

    Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), β-amyloid peptides 1-42 (Aβ(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau(181p) were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ(1-42)-associated cognitive change across all brain

  14. The Mediational Effects of FDG Hypometabolism on the Association between Cerebrospinal Fluid Biomarkers and Neurocognitive Function

    PubMed Central

    Dowling, N. Maritza; Johnson, Sterling C.; Gleason, Carey E.; Jagust, William J.

    2014-01-01

    Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer’s Disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau181p), β-amyloid 1–42 (Aβ1–42), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer’s Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer’s disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease’s Assessment Scale–cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau181p were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ1–42. FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ1–42 -associated cognitive change across all brain

  15. Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis

    PubMed Central

    Brittain, David C.; Howard, John J.; Oliver, JoAnne

    2015-01-01

    Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed. PMID:26063852

  16. Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis.

    PubMed

    Scheld, W M; Brodeur, J P

    1983-01-01

    The influence of methylprednisolone on the passage of ampicillin and gentamicin into and activity within cerebrospinal fluid was examined in two models of experimental meningitis. Steroid pretreatment reduced the concentrations of these drugs in purulent cerebrospinal fluid of rabbits with experimental pneumococcal and Escherichia coli meningitis (P less than 0.05). However, the resultant mean concentrations of these antibiotics in cerebrospinal fluid still exceeded the minimal bactericidal concentrations of the infecting organisms. The rate of bactericidal effect in vivo was unaffected by steroid therapy in each model. Methylprednisolone did not have deleterious effects on the course of treated experimental meningitis under these short-term (24-h) experiments. PMID:6338816

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

    PubMed

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

    2016-08-01

    The two primary molecular pathologies in Alzheimer's disease are amyloid-β plaques and tau-immunoreactive neurofibrillary tangles. Investigations into these pathologies have been restricted to cerebrospinal fluid assays, and positron emission tomography tracers that can image amyloid-β plaques. Tau tracers have recently been introduced into the field, although the utility of the tracer and its relationship to other Alzheimer biomarkers are still unknown. Here we examined tau deposition in 41 cognitively normal and 11 cognitively impaired older adults using the radioactive tau ligand (18)F-AV-1451 (previously known as T807) who also underwent a lumbar puncture to assess cerebrospinal fluid levels of total tau (t-tau), phosphorylated tau181 (p-tau181) and amyloid-β42 Voxel-wise statistical analyses examined spatial patterns of tau deposition associated with cognitive impairment. We then related the amount of tau tracer uptake to levels of cerebrospinal fluid biomarkers. All analyses controlled for age and gender and, when appropriate, the time between imaging and lumbar puncture assessments. Symptomatic individuals (Clinical Dementia Rating > 0) demonstrated markedly increased levels of tau tracer uptake. This elevation was most prominent in the temporal lobe and temporoparietal junction, but extended more broadly into parietal and frontal cortices. In the entire cohort, there were significant relationships among all cerebrospinal fluid biomarkers and tracer uptake, notably for tau-related cerebrospinal fluid markers. After controlling for levels of amyloid-β42, the correlations with tau uptake were r = 0.490 (P < 0.001) for t-tau and r = 0.492 (P < 0.001) for p-tau181 Within the cognitively normal cohort, levels of amyloid-β42, but not t-tau or p-tau181, were associated with elevated tracer binding that was confined primarily to the medial temporal lobe and adjacent neocortical regions. AV-1451 tau binding in the medial temporal, parietal, and frontal cortices

  18. Primary Spontaneous Cerebrospinal Fluid Leaks and Idiopathic Intracranial Hypertension

    PubMed Central

    Pérez, Mario A.; Bialer, Omer Y.; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie

    2014-01-01

    Introduction Idiopathic intracranial hypertension (IIH) is increasingly recognized as a cause of spontaneous cerebrospinal (CSF) leak in the ENT and neurosurgical literature. The diagnosis of IIH in patients with spontaneous CSF leaks is classically made a few weeks after surgical repair of the CSF leak when symptoms and signs of elevated intracranial pressure (ICP) appear. Methods Case reports and literature review. Two young obese women developed spontaneous CSF rhinorrhea related to an empty sella in one, and a cribriform plate encephalocele in the other. Both patients underwent surgical repair of the CSF leak. A few weeks later, they developed chronic headaches and bilateral papilledema. Lumbar punctures showed elevated CSF-opening pressures with normal CSF contents, with temporary improvement of headaches. A man with a three-year history of untreated IIH developed spontaneous CSF rhinorrhea. He experienced improvement of his headaches and papilledema after a CSF shunting procedure, and the rhinorrhea resolved after endoscopic repair of the leak. Results These cases and the literature review confirm a definite association between IIH and spontaneous CSF leak based on: 1) similar demographics; 2) increased ICP in some patients with spontaneous CSF leak after leak repair; 3) higher rate of leak recurrence in patients with raised ICP; 4) patients with intracranial hypertension secondary to tumors may develop CSF leak, confirming that raised ICP from other causes than IIH can cause CSF leak. Conclusions CSF leak may occasionally keep IIH patients symptom-free; however, classic symptoms and signs of intracranial hypertension may develop after the CSF leak is repaired, exposing these patients to a high risk of recurrence of the leak unless an ICP-lowering intervention is performed. PMID:24042170

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

    SciTech Connect

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

    2012-03-20

    Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-04-15

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

  2. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease

    PubMed Central

    Cruchaga, Carlos; Kauwe, John S.K.; Nowotny, Petra; Bales, Kelly; Pickering, Eve H.; Mayo, Kevin; Bertelsen, Sarah; Hinrichs, Anthony; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.

    2012-01-01

    The apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer's disease (AD). We have access to cerebrospinal fluid (CSF) and plasma APOE protein levels from 641 individuals and genome-wide genotyped data from 570 of these samples. The aim of this study was to test whether CSF or plasma APOE levels could be a useful endophenotype for AD and to identify genetic variants associated with APOE levels. We found that CSF (P = 8.15 × 10−4) but not plasma (P = 0.071) APOE protein levels are significantly associated with CSF Aβ42 levels. We used Mendelian randomization and genetic variants as instrumental variables to confirm that the association of CSF APOE with CSF Aβ42 levels and clinical dementia rating (CDR) is not because of a reverse causation or confounding effect. In addition the association of CSF APOE with Aβ42 levels was independent of the APOE ɛ4 genotype, suggesting that APOE levels in CSF may be a useful endophenotype for AD. We performed a genome-wide association study to identify genetic variants associated with CSF APOE levels: the APOE ɛ4 genotype was the strongest single-genetic factor associated with CSF APOE protein levels (P = 6.9 × 10−13). In aggregate, the Illumina chip single nucleotide polymorphisms explain 72% of the variability in CSF APOE protein levels, whereas the APOE ɛ4 genotype alone explains 8% of the variability. No other genetic variant reached the genome-wide significance threshold, but nine additional variants exhibited a P-value <10−6. Pathway mining analysis indicated that these nine additional loci are involved in lipid metabolism (P = 4.49 × 10−9). PMID:22821396

  3. Cerebrospinal Fluid Inflammatory Cytokines and Chemokines in Naturally Occurring Canine Spinal Cord Injury

    PubMed Central

    Taylor, Amanda R.; Welsh, C. Jane; Young, Colin; Spoor, Erich; Kerwin, Sharon C.; Griffin, John F.; Levine, Gwendolyn J.; Cohen, Noah D.

    2014-01-01

    Abstract Canine intervertebral disk herniation (IVDH) is a common, naturally occurring form of spinal cord injury (SCI) that is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury mechanisms. Here, we characterized cerebrospinal fluid (CSF) cytokines, and chemokines in dogs with acute, surgically treated, thoracolumbar IVDH (n=39) and healthy control dogs (n=21) to investigate early inflammatory events after SCI. A bioplex system was used to measure interleukin (IL)-2, -6, -7, -8, -10, -15, and -18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), keratinocyte chemoattractant (KC)-like protein, IFN-γ-inducible protein-10, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha. Cytokine and chemokine concentrations in the CSF of healthy and SCI dogs were compared and, in SCI dogs, were correlated to the duration of SCI, behavioral measures of injury severity at the time of sampling, and neurological outcome 42 days post-SCI as determined by a validated ordinal score. IL-8 concentration was significantly higher in SCI cases than healthy controls (p=0.0013) and was negatively correlated with the duration of SCI (p=0.042). CSF MCP-1 and KC-like protein were positively correlated with CSF microprotein concentration in dogs with SCI (p<0.0001 and p=0.004). CSF MCP-1 concentration was negatively associated with 42-day postinjury outcome (p<0.0001). Taken together, these data indicate that cytokines and chemokines present after SCI in humans and rodent models are associated with SCI pathogenesis in canine IVDH. PMID:24786364

  4. Penetration of doxycycline into cerebrospinal fluid in patients treated for suspected Lyme neuroborreliosis.

    PubMed Central

    Dotevall, L; Hagberg, L

    1989-01-01

    Twelve patients were treated orally with 100 mg of doxycycline twice a day (b.i.d.) and 10 patients were treated with 200 mg b.i.d. for suspected tick-borne neuroborreliosis (Lyme borreliosis). At 5 to 8 days after the start of therapy, the mean concentrations in serum were 4.7 micrograms/ml for the doxycycline dose of 100 mg b.i.d. and 7.5 micrograms/ml for 200 mg b.i.d., 2 to 3 h after the last drug administration. The corresponding levels for cerebrospinal fluid were 0.6 and 1.1 micrograms/ml. Since a doxycycline concentration in cerebrospinal fluid above the estimated MIC for Borrelia burgdorferi (0.6 to 0.7 microgram/ml) is wanted in patients treated for severe neuroborreliosis, the higher dose is preferable. PMID:2782858

  5. An improved dinitrosalicylic acid method for determining blood and cerebrospinal fluid sugar levels.

    PubMed

    MOHUN, A F; COOK, I J

    1962-03-01

    A development of a technique for estimating sugar in blood, cerebrospinal fluid, etc., is described, using 3:5-dinitrosalicylic acid (D.N.S.A.) originally introduced by Sumner (1921). Results can be obtained in less than 10 minutes if required. The method is well suited to the estimation of random blood sugars and the handling of diabetic clinic requirements in hospital laboratories. The reagents are cheap, stable, and easily prepared. The results are very close to true glucose values in blood and cerebrospinal fluid. The technique has justified its existence in a busy clinical laboratory on the grounds of simplicity and rapidity, and is sufficiently precise for all ordinary work. PMID:14475095

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

    PubMed

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

    2016-02-01

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

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

    PubMed

    West, Wanda; Ehrmann, Jon; Johnson, Wendy

    2014-08-01

    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 (β-amyloid (Aβ)) 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

  8. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease

    PubMed Central

    Gui, YaXing; Liu, Hai; Zhang, LiShan; Lv, Wen; Hu, XingYue

    2015-01-01

    The differential diagnosis of Parkinson's diseases (PD) is challenging, especially in the early stages of the disease. We developed a microRNA profiling strategy for exosomal miRNAs isolated from cerebrospinal fluid (CSF) in PD and AD. Sixteen exosomal miRNAs were up regulated and 11 miRNAs were under regulated significantly in PD CSF when compared with those in healthy controls (relative fold > 2, p < 0.05). MiR-1 and miR-19b-3p were validated and significantly reduced in independent samples. While miR-153, miR-409-3p, miR-10a-5p, and let-7g-3p were significantly over expressed in PD CSF exosome. Bioinformatic analysis by DIANA-mirPath demonstrated that Neurotrophin signaling, mTOR signaling, Ubiquitin mediated proteolysis, Dopaminergic synapse, and Glutamatergic synapse were the most prominent pathways enriched in quantiles with PD miRNA patterns. Messenger RNA (mRNA) transcripts [amyloid precursor protein, APP), α-synuclein (α-syn), Tau, neurofilament, light gene (NF-L), DJ-1/PARK7, Fractalkine and Neurosin] and long non-coding RNAs (RP11-462G22.1 and PCA3) were differentially expressed in CSF exosomes in PD and AD patients. These data demonstrated that CSF exosomal RNA molecules are reliable biomarkers with fair robustness in regard to specificity and sensitivity in differentiating PD from healthy and diseased (AD) controls. PMID:26497684

  9. Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability.

    PubMed

    Fourier, Anthony; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Quadrio, Isabelle; Perret-Liaudet, Armand

    2015-09-20

    A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and β-amyloid peptides (Aβ42 and Aβ40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations. PMID:26141614

  10. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

    PubMed Central

    Krasota, Alexandr; Loginovskih, Natalia; Ivanova, Olga; Lipskaya, Galina

    2016-01-01

    Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF. PMID:26751470

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

    NASA Astrophysics Data System (ADS)

    Harbater, Osnat; Gannot, Israel

    2014-03-01

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

  12. Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.

    PubMed

    Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D

    1999-01-01

    We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis. PMID:10604277

  13. Gender-dependent levels of hyaluronic acid in cerebrospinal fluid of patients with neurodegenerative dementia.

    PubMed

    Nielsen, Henrietta M; Palmqvist, Sebastian; Minthon, Lennart; Londos, Elisabet; Wennström, Malin

    2012-03-01

    Numerous reports over the years have described neuroinflammatory events and vascular changes in neurodegenerative diseases such as Alzheimers disease (AD) and Dementia with Lewy bodies (DLB). Interestingly, recent reports from other research areas suggest that inflammatory and vascular processes are influenced by gender. These findings are intriguing from the perspective that women show a higher incidence of AD and warrant investigations on how gender influences various processes in neurodegenerative dementia. In the current study we measured the cerebrospinal fluid (CSF) and plasma concentrations of hyaluroinic acid (HA), an adhesionmolecule known to regulate both vascular and inflammatory processes, in AD and DLB patients as well as in healthy elders. Our analysis showed that male AD and DLB patients had almost double the amount of HA compared to female patients whereas no gender differences were observed in the controls. Furthermore, we found that CSF levels of HA in foremost female AD patients correlated with various AD related biomarkers. Correlations between HA levels and markers of inflammation and vascular changes were only detected in female AD patients but in both male and female DLB patients. We conclude that HA may be linked to several pathological events present in AD, as reflected in CSF protein concentrations. The HA profile in CSF, but not in plasma, and associations to other markers appear to be gender-dependent which should be taken into account in clinical examinations and future biomarker studies. PMID:22191565

  14. Immunocytochemical demonstration of feline infectious peritonitis virus within cerebrospinal fluid macrophages.

    PubMed

    Ives, Edward J; Vanhaesebrouck, An E; Cian, Francesco

    2013-12-01

    A 4-month-old female entire domestic shorthair cat presented with an acute onset of blindness, tetraparesis and subsequent generalised seizure activity. Haematology and serum biochemistry demonstrated a moderate, poorly regenerative anaemia, hypoalbuminaemia and hyperglobulinaemia with a low albumin:globulin ratio. Serology for feline coronavirus antibody was positive with an elevated alpha-1 acid glycoprotein. Analysis of cisternal cerebrospinal fluid (CSF) demonstrated markedly elevated protein and a mixed, predominately neutrophilic pleocytosis. Immunocytochemistry for feline coronavirus was performed on the CSF, with positive staining observed inside macrophages. The cat was subsequently euthanased, and both histopathology and immunohistochemistry were consistent with a diagnosis of feline infectious peritonitis. This is the first reported use of immunocytochemistry for detection of feline coronavirus within CSF macrophages. If this test proves highly specific, as for identification of feline coronavirus within tissue or effusion macrophages, it would be strongly supportive of an ante-mortem diagnosis of feline infectious peritonitis in cats with central nervous system involvement without the need for biopsy. PMID:23744728

  15. Cerebrospinal fluid T-regulatory cells recognize Borrelia burgdorferi NAPA in chronic Lyme borreliosis.

    PubMed

    Amedei, A; Codolo, G; Ozolins, D; Ballerini, C; Biagioli, T; Jaunalksne, I; Zilevica, A; D Elios, S; De Bernard, M; D' Elios, M M

    2013-01-01

    The NapA protein of B. burgdorferi is essential for the persistence of spirochetes in ticks. One of the most intriguing aspects of NapA is its potential to interfere with the host immune system. Here, we investigated the role of the acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced in microglia cells and CSF T cells following NapA stimulation. We report here that NapA induced a regulatory T (Treg) response in the CSF of patients with chronic Lyme borreliosis and it is able to expand this suppressive response by promoting the production of TGF-beta and IL-10 by microglia cells. Collectively, these data strongly support a central role of NapA in promoting both Treg response and immune suppression in the CSF of patients with chronic Lyme borreliosis and suggest that NapA and the Treg pathway may represent novel therapeutic targets for the prevention and treatment of the disease. PMID:24355226

  16. Evaluation of the effect of oral omeprazole on canine cerebrospinal fluid production: A pilot study.

    PubMed

    Girod, M; Allerton, F; Gommeren, K; Tutunaru, A C; de Marchin, J; Van Soens, I; Ramery, E; Peeters, D

    2016-03-01

    Administration of omeprazole by ventriculo-cisternal perfusion or intravenously has been shown to decrease cerebrospinal fluid (CSF) production in dogs and rabbits. Oral omeprazole has consequently been recommended to reduce CSF production in dogs with conditions in which clinical signs may be attributable to an accumulation of CSF in the central nervous system (e.g. hydrocephalus, syringomyelia). The albumin quotient (QAlb), the ratio between CSF and serum albumin concentration, has been proposed as a reliable means to evaluate CSF production; decreasing CSF production should cause an increase in QAlb. The aims of this study were to assess the effect of oral administration of omeprazole on QAlb in dogs and to compare two methods to assess CSF albumin concentration. Fifteen healthy Beagle dogs received omeprazole (1.2 mg/kg/day) orally for 14 days; CSF and blood were obtained before and after treatment. CSF albumin concentrations were evaluated by nephelometry and high-resolution protein electrophoresis. Regardless of the method used for measuring albumin, QAlb did not change significantly following oral omeprazole administration, suggesting that CSF production in healthy dogs may not be affected by chronic oral therapy with omeprazole. PMID:26852945

  17. Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development.

    PubMed

    Alonso, M I; Martín, C; Carnicero, E; Bueno, D; Gato, A

    2011-07-01

    Embryonic-cerebrospinal fluid (E-CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E-CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E-CSF contains all-trans-retinol and retinol-binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic-rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E-CSF helps to control RA synthesis in the IsO by means of the RBP and all-trans-retinol it contains; (2) E-CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E-CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. PMID:21594951

  18. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification.

    PubMed

    Krasota, Alexandr; Loginovskih, Natalia; Ivanova, Olga; Lipskaya, Galina

    2016-01-01

    Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF. PMID:26751470

  19. Monoamine metabolite concentrations in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia.

    PubMed Central

    Palmer, A M; Sims, N R; Bowen, D M; Neary, D; Palo, J; Wikstrom, J; Davison, A N

    1984-01-01

    Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxy indoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) from control subjects and patients of both presenile and senile age with histologically verified Alzheimer's dementia. CSF HVA increased with age in control but not in Alzheimer patients. HVA and 5-HIAA in the CSF of presenile Alzheimer patients was lower than that of age matched control subjects. PMID:6204017

  20. Breast Capsular Cerebrospinal Fluid Collection from Migration of a Ventriculoperitoneal Shunt Catheter

    PubMed Central

    Knaus, William J.; Kamali, Parisa; Chun, Yoon

    2016-01-01

    Summary: In this case report we have described an unusual complication of ventriculoperitoneal shunt migration into a breast implant capsule. The patient was appropriately diagnosed with computed tomographic imaging and successfully managed with shunt revision and cerebrospinal fluid aspiration. Given the high complication profile of ventriculoperitoneal shunt catheters, this case suggests an opportunity for improved perioperative communication between plastic surgeons and neurosurgeons in patients with breast implants. Coordination regarding the subcutaneous catheter tunneling may hopefully minimize the risk of this complication. PMID:27257570

  1. Tension pneumocephalus complicating ventriculoperitoneal shunt for cerebrospinal fluid rhinorrhoea: case report.

    PubMed

    Ikeda, K; Nakano, M; Tani, E

    1978-04-01

    A case of spontaneous nontraumatic cerebrospinal fluid rhinorrhoea secondary to aqueductal stenosis is reported. The patient required direct repair of the fistula after the insertion of a ventriculoperitoneal shunt for aqueductal stenosis. We emphasise an unusual complication of tension pneumocephalus in a case where the shunt patency had been substantiated. Intracranial pressure fall due to the siphon effect in the ventriculoperitoneal shunt tubing in the erect position might be responsible for ingress of an excessive amount of air. PMID:650239

  2. Cerebrospinal fluid biomarkers in parkinsonian conditions: an update and future directions

    PubMed Central

    Magdalinou, Nadia; Lees, Andrew J; Zetterberg, Henrik

    2014-01-01

    Parkinsonian diseases comprise a heterogeneous group of neurodegenerative disorders, which show significant clinical and pathological overlap. Accurate diagnosis still largely relies on clinical acumen; pathological diagnosis remains the gold standard. There is an urgent need for biomarkers to diagnose parkinsonian disorders, particularly in the early stages when diagnosis is most difficult. In this review, several of the most promising cerebrospinal fluid candidate markers will be discussed. Their strengths and limitations will be considered together with future developments in the field. PMID:24691581

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

    PubMed

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

    2016-01-01

    The clinical case is presented on a patient with an extensive sacral dysraphism, a history of myelomeningocele surgical repair in her childhood, as well as tethered cord syndrome. The patient was also diagnosed with pseudomeningocele and a cerebrospinal fluid cutaneous fístula. A surgical approach was used, with encouraging results being obtained in the clinical outcome of the patient. A review of the literature was performed to support the surgical decision in this case. PMID:26936617

  4. Fistula of stapes footplate caused by pulsatile cerebrospinal fluid in inner ear malformation.

    PubMed

    Hoppe, F; Hagen, R; Hofmann, E

    1997-01-01

    Congenital malformations of the inner ear are well described, though the combination with cerebrospinal fluid (CSF) leaks remains controversial. In this paper a case of a bilateral Mondini malformation with a CSF otorrhea on one side is reported. The malformed stapes contains a perforation in the middle of the footplate and associated thinning analogous to a pothole in a mountain stream. The histological findings support the hypothesis of pulsatile flow of CSF as origin of the perforation of the footplate. PMID:9166882

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

    PubMed Central

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

    2009-01-01

    Background To date hydrocephalus researchers acknowledge the need for rigorous but utilitarian fluid mechanics understanding and methodologies in studying normal and hydrocephalic intracranial dynamics. Pressure volume models and electric circuit analogs introduced pressure into volume conservation; but control volume analysis enforces independent conditions on pressure and volume. Previously, utilization of clinical measurements has been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Methods Control volume analysis is presented to introduce the reader to the theoretical background of this foundational fluid mechanics technique for application to general control volumes. This approach is able to directly incorporate the diverse measurements obtained by clinicians to better elucidate intracranial dynamics and progression to disorder. Results Several examples of meaningful intracranial control volumes and the particular measurement sets needed for the analysis are discussed. Conclusion Control volume analysis provides a framework to guide the type and location of measurements and also a way to interpret the resulting data within a fundamental fluid physics analysis. PMID:19772652

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

    PubMed

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

    2005-04-01

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

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

    SciTech Connect

    Engbaek, F.; Voldby, B

    1982-04-01

    A direct radioimmunoassay is described for serotonin (5-hydroxytryptamine) in cerebrospinal fluid, platelet-poor plasma, and serum. Antisera in rabbits was raised against serotonin diazotized to a conjugate of bovine albumin and D,L-p-aminophenylalanine. Polyethylene glycol, alone or in combination with anti-rabbit immunoglobulins, is used to separate bound and unbound tritiated serotonin. The minimum concentration of serotonin detectable is 2 nmol/L in a 200-..mu..L sample. Within-day precision (CV) is 4.3% between-day precision 7.7%. Analytical recoveries of serotonin are 109% and 101% for cerebrospinal fluid and plasma, respectively. Tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol do not interfere with the assay. However, 5-methoxytryptamine and tryptamine cross react. Of samples of cerebrospinal fluid from patients with disc herniations (n=21) or low-pressure hydrocephalus (n=10), one-third had concentrations of 2-4 nmol/L and two-thirds were below the minimum detectable concentration. The observed range for the concentration of serotonin in plasma of 14 normal subjects was 5-14 nmol/L (mean +/- SD, 9 +/- 3 nmol/L). The observed ranges for serotonin in serum were: for 10 women 520-900 (mean +/- SD: 695 +/- 110) nmol/L and for 10 men 380-680 (520 +/- 94) nmol/L.

  8. Effect of Embryonic Cerebrospinal Fluid on Proliferation and Differentiation of Neuroprogenitor Cells

    PubMed Central

    Yari, Siamak; Parivar, Kazem; Nabiuni, Mohammad; Keramatipour, Mohammad

    2013-01-01

    Objective: Embryonic cerebrospinal fluid (e-CSF) has an important role in development of embryonic and adult brain. Proteomic analysis suggests that this fluid has many morphogenes and cytokines that alter in time and space throughout embryonic life. The aim of this study was to evaluate the developmental effect of embryonic CSF on proliferation and differentiation of neuroprogenitor cells in different gestational age. Materials and Methods: In this In this experimental study, we examined the role of e- CSF on proliferation and differentiation of neuroprogenitor cells using neurosphere culture method. Neurospheres size analysis and MTT assay were used to assess cell proliferation after four days in vitro. Glial differentiation study was carried out by immunocytochemistry. Neurospheres size and percentage of glial fibrialy acidic protein (GFAP) positive cells were measured by image analyzer (image J). The data were analyzed by one-way ANOVA, followed by the Tukey’s post hoc test. Data were expressed as mean ± SEM, and differences were considered significant when p<0.05, 0.01 and 0.001. Results: Viability and proliferation of neuro progenitor cells in cultures conditioned with E16 CSF and E18 CSF were significantly increased compare to control group. A dramatic decrease in percentage of GFAP-positive cells was found following the application of CSF from E16 and E18 embryos, but not E20 CSF. Conclusion: Our data suggest that, e-CSF altered proliferation and differentiation of neuro progenitor cells in age dependent manner. E16 and E18 CSF enhanced proliferation and viability of neuro progenitor cells, and inhibited differentiation to glial fate in comparison with control group. PMID:23700558

  9. Diagnostic accuracy of urinary reagent strip to determine cerebrospinal fluid chemistry and cellularity

    PubMed Central

    Joshi, Deepti; Kundana, Keerthi; Puranik, Apurva; Joshi, Rajnish

    2013-01-01

    Background: The gold standard for diagnosis of meningitis depends on cerebrospinal fluid (CSF) examination by microscopy, biochemistry, and culture, which require an experienced microscopist and laboratory support. We conducted this study to determine if urinary reagent strip is useful to make a semi-quantitative assessment of protein, glucose, and presence of leukocyte esterase in CSF. Materials and Methods: All consecutive CSF samples were evaluated in a blinded fashion. CSF was tested using Combur-10 urinary reagent strip as an index test, and CSF microscopy and biochemistry as reference standards. Combur-10 (Boehringer Mannheim) is a urinary reagent strip used to estimate ten parameters including protein, glucose, and leukocytes. We estimated diagnostic accuracy of each index test using corresponding cut-off levels (glucose 1 + vs. CSF glucose >50 mg/dL; protein 1 + and 2 + vs. CSF protein >30 mg/dL and >100 mg/dL; leukocyte esterase positivity vs. >10 granulocytes in CSF sample). We constructed receiver operating curves (ROC) to evaluate overall performance of index tests and estimated area under the curve (AUC). Results: CSF samples of 75 patients were included in the study. All the three indicator tests (CSF cells, protein, and glucose) were normal in 17 (22.6%) samples. Of the three tests, diagnostic accuracy of protein estimation (1 + or more on reagent strip) was best for detection of CSF proteins greater than 30 mg/dL [sensitivity 98.1% (95% CI 90.1-100%); specificity 57.1% (95% CI 34-78.2%)], with AUC of 0.97. Sensitivity and specificity for 2 + on reagent strip and CSF protein > 100 mg/dL were 92.6% (95% CI 75.1-99.1) and 87.5% (95% CI 74.8-95.3), respectively, with AUC of 0.96 (95% CI 0.92-1.01). Leukocyte esterase positivity by test strip had a sensitivity of 85.2 (95% CI 66.3-95.8%) and specificity of 89.6 (95% CI 77.3-96.5%) for detection of CSF granulocytes of more than 10/mm3. Conclusion: Existing urinary reagent strips can be used to diagnose

  10. [Spontaneous cerebrospinal fluid leak may cause intracranial hypotension].

    PubMed

    Christiansen, Ingelise

    2015-01-01

    Spontaneous intracranial hypotension (SIH) is often misinterpreted as migraine or tension headache. This type of headache is, however, orthostatic and resolves in supine position. CT scan/MRI of the brain has characteristic findings, enhancement of the pachymeninges and bilateral hygroma. An extreme situation of a 70-year-old woman with sagging midbrain is described in this case report. Although this type of headache may be caused by a dural fistula with spinal fluid leak it is not necessary to locate the lesion with myelografi/MR. Timely treatment with an epidural blood patch at any lumbal level could prevent potentially life-threatening complications and the headache resolved within hours/few days. PMID:25557447