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Sample records for cerebrospinal fluid protein

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

    PubMed

    Finley, P R; Williams, R J

    1983-01-01

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

  2. 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

  3. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression.

    PubMed

    Southwell, Amber L; Smith, Stephen E P; Davis, Tessa R; Caron, Nicholas S; Villanueva, Erika B; Xie, Yuanyun; Collins, Jennifer A; Ye, Min Li; Sturrock, Aaron; Leavitt, Blair R; Schrum, Adam G; Hayden, Michael R

    2015-07-15

    Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker.

  4. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression

    PubMed Central

    Southwell, Amber L.; Smith, Stephen E.P.; Davis, Tessa R.; Caron, Nicholas S.; Villanueva, Erika B.; Xie, Yuanyun; Collins, Jennifer A.; Li Ye, Min; Sturrock, Aaron; Leavitt, Blair R.; Schrum, Adam G.; Hayden, Michael R.

    2015-01-01

    Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker. PMID:26174131

  5. The ontogenetic development of concentration differences for protein and ions between plasma and cerebrospinal fluid in rabbits and rats.

    PubMed

    Amtorp, O; Sorensen, S C

    1974-12-01

    1. The purpose of this study was to study in rats and rabbits the ontogenetic development of the blood-brain barrier to macromolecules and the ontogenetic development of concentration differences between plasma and cerebrospinal fluid for ions which are known to be transported actively across the choroid plexus and the blood-brain barrier.2. By comparing the development of concentration differences for ions with the development of the blood-brain barrier to macromolecules we wanted to evaluate an eventual relationship between the development of these two functions of the blood-brain barrier.3. The concentration of protein in cerebrospinal fluid and plasma was measured in foetal, juvenile and adult rabbits and in new-born, juvenile and adult rats. The concentration of protein was similar in rabbit foetuses at 23 days of gestational age (term at 31 days) and in new-born rats, and the ratio decreases at approximately the same rate in the two species.4. The high concentration of proteins in cerebrospinal fluid might reflect either a high rate of entry of protein into the brain or a low production rate of cerebrospinal fluid. Injection of Diamox(R) (100 mg/kg) 2 hr before sampling of cerebrospinal fluid did not change the concentration of protein in cerebrospinal fluid in new-born rats whereas it increased the concentration in older rats. This finding suggests that new-born rat produces little (if any) cerebrospinal fluid suggesting that the high concentration of protein in cerebrospinal fluid in new-born rats reflect a low rate of turnover of cerebrospinal fluid.5. The concentration of sodium, potassium, chloride and magnesium in plasma and cisternal cerebrospinal fluid was measured in rabbits of different age, from 23 days of gestation until adulthood, and in rats of different ages from birth until adulthood.6. Concentration differences between plasma and cerebrospinal fluid for these were established in the youngest animals examined, indicating that the active

  6. Cerebrospinal Fluid from Alzheimer's Disease Patients Contains Fungal Proteins and DNA.

    PubMed

    Alonso, Ruth; Pisa, Diana; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    The identification of biomarkers for Alzheimer's disease is important for patient management and to assess the effectiveness of clinical intervention. Cerebrospinal fluid (CSF) biomarkers constitute a powerful tool for diagnosis and monitoring disease progression. We have analyzed the presence of fungal proteins and DNA in CSF from AD patients. Our findings reveal that fungal proteins can be detected in CSF with different anti-fungal antibodies using a slot-blot assay. Additionally, amplification of fungal DNA by PCR followed by sequencing distinguished several fungal species. The possibility that these fungal macromolecules could represent AD biomarkers is discussed.

  7. Spectrophotometric study of total protein-albumin methods applied to cerebrospinal fluid.

    PubMed

    Artiss, J D; Thibert, R J; Zak, B

    1981-02-01

    A spectrophotometric study was carried out for three proteins assays when modification of their serum procedures using bromcresol green, bromcresol purple and biuret reagents were applied to the determinations of total proteins and albumin in cerebrospinal fluids. A novel concentration device wherein the sample itself was used as the primary diluent for the three reagents concentrated to contain the proper amounts of chemicals in smaller volumes than suggested in their serum procedures allowed reasonable absorbance signals to be obtained. Low molecular weight molecules were separated from the albumin and globulins of the fluids by centrifugal ultrafiltration using a 25K cutoff and spectra were obtained for both high and low molecular weight fractions. Some materials were obtained in the separated ultrafiltrates which gave reactions with all three reagents, reactions which either overlapped the spectra of the albumin reactions or superimposed the spectra obtained with the total protein reaction. A screening procedure for cerebrospinal fluid total proteins or centrifugally ultrafiltered albumin appears reasonable as an inference from studies made, although further elucidation of the low molecular weight fractions in needed as a confirmation device.

  8. Application of a silver-binding assay to the determination of protein in cerebrospinal fluid.

    PubMed

    Krystal, G; Lam, V; Schreiber, W E

    1989-05-01

    We evaluated a silver-binding assay for use in measuring total protein in cerebrospinal fluid. The advantage of this procedure over other methods is that, because of its sensitivity, it requires only a 0.5-microL sample. The procedure, which takes approximately 40 min to complete, involves dilution of 0.5-microL samples to 1 mL with distilled water containing sodium dodecyl sulfate, followed by addition of glutaraldehyde and an ammoniacal silver solution. After color development for 30 min, the reaction is terminated with sodium thiosulfate and the absorbance is measured at 420 nm. This assay displayed within-run and day-to-day precision (CV) of 3.1% to 13% over the range of 210 to 1370 mg/L. It showed substantially less protein-to-protein variation than the Coomassie Blue dye-binding procedure when tested with albumin, globulin, and transferrin. It also yielded an accurate estimation of hemoglobin. Moreover, preliminary studies suggested that it was capable of quantifying immunoglobulin light chains and glycoproteins. In a study of 54 human cerebrospinal fluid samples, results of the silver-binding assay corresponded more closely with those obtained with a rate biuret assay (intraclass correlation coefficient = 0.91) than did either the dye-binding or classical Lowry methods.

  9. 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.

  10. Detection of Protein Aggregates in Brain and Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

    PubMed Central

    David, Monique Antoinette; Tayebi, Mourad

    2014-01-01

    Studies of the properties of soluble oligomer species of amyloidogenic proteins, derived from different proteins with little sequence homology, have indicated that they share a common structure and may share similar pathogenic mechanisms. Amyloid β, tau protein, as well as amyloid precursor protein normally associated with Alzheimer’s disease and Parkinson’s disease were found in lesions and plaques of multiple sclerosis patients. The objective of the study is to investigate whether brain and cerebrospinal fluid (CSF) samples derived from multiple sclerosis patients demonstrate the presence of soluble oligomers normally associated with protein-misfolding diseases such as Alzheimer’s disease. We have used anti-oligomer monoclonal antibodies to immunodetect soluble oligomers in CSF and brain tissues derived from multiple sclerosis patients. In this report, we describe the presence of soluble oligomers in the brain tissue and cerebral spinal fluid of multiple sclerosis patients detected with our monoclonal anti-oligomer antibodies with Western blot and Sandwich enzyme-linked immunosorbent assay (sELISA). These results might suggest that protein aggregation plays a role in multiple sclerosis pathogenesis although further and more refined studies are needed to confirm the role of soluble aggregates in multiple sclerosis. PMID:25520699

  11. Detection of glial fibrillary acidic protein and neurofilaments in the cerebrospinal fluid of patients with neurocysticercosis.

    PubMed

    Quintanar, J Luis; Franco, Luis Manuel; Salinas, Eva

    2003-07-01

    Neurocysticercosis (NCC) is an infection caused by Taenia solium larval metacestodes in the central nervous system. The glial fibrillary acidic protein (GFAP) and neurofilaments (NFs) can be used as markers of glial and neuronal damage, respectively. We studied the GFAP and NFs of 68, 160 and 200 kDa in the cerebrospinal fluid (CSF) of patients with NCC by Western blotting. Our results showed that patients with NCC had significantly elevated GFAP levels in the CSF compared with the control, whereas NFs of 68, 160 and 200 kDa were not detected in the CFS of NCC patients. We concluded that GFAP could be used as a marker of glial damage in the CFS of NCC patients.

  12. Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease*S⃞

    PubMed Central

    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.

    2009-01-01

    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

  13. 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

  14. Insights into the human brain proteome: Disclosing the biological meaning of protein networks in cerebrospinal fluid.

    PubMed

    Bastos, Paulo; Ferreira, Rita; Manadas, Bruno; Moreira, Paula I; Vitorino, Rui

    2017-04-10

    Cerebrospinal fluid (CSF) is an excellent source of biological information regarding the nervous system, once it is in close contact and accurately reflects alterations in this system. Several studies have analyzed differential protein profiles of CSF samples between healthy and diseased human subjects. However, the pathophysiological mechanisms and how CSF proteins relate to diseases are still poorly known. By applying bioinformatics tools, we attempted to provide new insights on the biological and functional meaning of proteomics data envisioning the identification of putative disease biomarkers. Bioinformatics analysis of data retrieved from 99 mass spectrometry (MS)-based studies on CSF profiling highlighted 1985 differentially expressed proteins across 49 diseases. A large percentage of the modulated proteins originate from exosome vesicles, and the majority are involved in either neuronal cell growth, development, maturation, migration, or neurotransmitter-mediated cellular communication. Nevertheless, some diseases present a unique CSF proteome profile, which were critically analyzed in the present study. For instance, 48 proteins were found exclusively upregulated in the CSF of patients with Alzheimer's disease and are mainly involved in steroid esterification and protein activation cascade processes. A higher number of exclusively upregulated proteins were found in the CSF of patients with multiple sclerosis (76 proteins) and with bacterial meningitis (70 proteins). Whereas in multiple sclerosis, these proteins are mostly involved in the regulation of RNA metabolism and apoptosis, in bacterial meningitis the exclusively upregulated proteins participate in inflammation and antibacterial humoral response, reflecting disease pathogenesis. The exploration of the contribution of exclusively upregulated proteins to disease pathogenesis will certainly help to envision potential biomarkers in the CSF for the clinical management of nervous system diseases.

  15. 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).

  16. 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.

  17. Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid

    PubMed Central

    Chan, Xin Yue

    2016-01-01

    Background Meningitis is a major cause of mortality in tuberculosis (TB). It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb) might have genetic traits associated with neurotropism. Methods In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF) of patients presenting with tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. Results Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions) and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate)/PPE (proline-proline-glutamate), transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. Discussion The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB meningeal

  18. Simultaneous quantification of Myelin Basic Protein and Tau proteins in cerebrospinal fluid and serum of Multiple Sclerosis patients using nanoimmunosensor.

    PubMed

    Derkus, Burak; Acar Bozkurt, Pinar; Tulu, Metin; Emregul, Kaan C; Yucesan, Canan; Emregul, Emel

    2017-03-15

    This study was aimed at the development of an immunosensor for the simultaneous quantification of Myelin Basic Protein (MBP) and Tau proteins in cerebrospinal fluid (CSF) and serum, obtained from Multiple Sclerosis (MS) patients. The newly developed GO/pPG/anti-MBP/anti-Tau nanoimmunosensor has been established by immobilization of MBP and Tau antibodies. The newly developed nanoimmunosensor was tested, optimized and characterized using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The developed nanoimmunosensor was seen to have detection limits of 0.30nM for MBP and 0.15nM for Tau proteins which were sufficient for the levels to be analysed in neuro-clinic. The clinical study performed using CSF and serum of MS patients showed that the designed nanoimmunosensor was capable of detecting the proteins properly, that were essentially proven by ELISA.

  19. Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury

    PubMed Central

    Anderson, Kimberly M.; Welsh, C. Jane; Young, Colin; Levine, Gwendolyn J.; Kerwin, Sharon C.; Boudreau, C. Elizabeth; Reyes, Ismael; Mondragon, Armando; Griffin, John F.; Cohen, Noah D.

    2015-01-01

    Abstract Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target. PMID:26186466

  20. Assay of gentamicin in cerebrospinal fluid.

    PubMed Central

    Deacon, S

    1976-01-01

    A comparison of standard curves obtained from a conventional plate diffusion assay method revealed significant differences when gentamicin standards were made up in different media. Standards made up in distilled water resulted in a curve which differed from that of standards made up in pooled human cerebrospinal fluid by a factor of up to 4. When the assay medium was supplemented with 0-5% sodium chloride, the difference between the two standard curves was reduced to a factor of about 1-5. The curve obtained from standards made up in 150 mM sodium chloride/4-5 mM calcium chloride correlated well with that from standards made up in cerebrospinal fluid. There was no evidence of gentamicin being bound to protein in the cerebrospinal fluid. PMID:956457

  1. Correlations of Ventricular Enlargement with Rheologically Active Surfactant Proteins in Cerebrospinal Fluid

    PubMed Central

    Schob, Stefan; Weiß, Alexander; Dieckow, Julia; Richter, Cindy; Pirlich, Mandy; Voigt, Peter; Surov, Alexey; Hoffmann, Karl-Titus; Quaeschling, Ulf; Preuß, Matthias

    2017-01-01

    Purpose: Surfactant proteins (SPs) are involved in the regulation of rheological properties of body fluids. Concentrations of SPs are altered in the cerebrospinal fluid (CSF) of hydrocephalus patients. The common hallmark of hydrocephalus is enlargement of the brain ventricles. The relationship of both phenomena has not yet been investigated. The aim of this study was to evaluate the association between SP concentrations in the CSF and enlargement of the brain ventricles. Procedures: Ninty-six individuals (41 healthy subjects and 55 hydrocephalus patients) were included in this retrospective analysis. CSF specimens were analyzed for SP-A, SP-B, SP-C and SP-D concentrations by use of enzyme linked immunosorbent assays (ELISA). Ventricular enlargement was quantified in T2 weighted (T2w) magnetic resonance imaging (MRI) sections using an uni-dimensional (Evans’ Index) and a two-dimensional approach (lateral ventricles area index, LVAI). Results: CSF-SP concentrations (mean ± standard deviation in ng/ml) were as follows: SP-A 0.71 ± 0.58, SP-B 0.18 ± 0.43, SP-C 0.89 ± 0.77 and SP-D 7.4 ± 5.4. Calculated values of Evans’ Index were 0.37 ± 0.11, a calculation of LVAI resulted in 0.18 ± 0.15 (each mean ± standard deviation). Significant correlations were identified for Evans’ Index with SP-A (r = 0.388, p < 0.001) and SP-C (r = 0.392, p < 0.001), LVAI with SP-A (r = 0.352, p = 0.001), SP-C (r = 0.471, p < 0.001) and SP-D (r = 0.233, p = 0.025). Furthermore, SP-C showed a clear inverse correlation with age (r = −0.357, p = 0.011). Conclusion: The present study confirmed significant correlations between SPs A, C and D in the CSF with enlargement of the inner CSF spaces. In conclusion, SPs clearly play an important role for CSF rheology. CSF rheology is profoundly altered in hydrocephalic diseases, however, diagnosis and therapy of hydrocephalic conditions are still almost exclusively based on ventricular enlargement. Until now it was unclear, whether the

  2. Cerebrospinal fluid culture

    MedlinePlus

    ... Alternative Names Culture - CSF; Spinal fluid culture; CSF ... In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 23d ed. Philadelphia, PA: Elsevier; ...

  3. 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.

  4. Glial fibrillar acidic protein in the cerebrospinal fluid of Alzheimer's disease, dementia with Lewy bodies, and frontotemporal lobar degeneration.

    PubMed

    Ishiki, Aiko; Kamada, Maki; Kawamura, Yuki; Terao, Chiaki; Shimoda, Fumiko; Tomita, Naoki; Arai, Hiroyuki; Furukawa, Katsutoshi

    2016-01-01

    Biomarkers in the cerebrospinal fluid (CSF) are currently regarded as indispensable indicators for accurate differential diagnosis of neurodegenerative disorders. Although high levels of astrocyte-secreted glial fibrillar acidic protein (GFAP) in the CSF of patients with Alzheimer's disease (AD) have been reported, the levels of GFAP in the CSF have not been fully investigated in other neurological disorders that cause dementia, such as dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). In this study, we determined the levels of GFAP in the CSF of healthy control subjects and AD, DLB, and FTLD patients to address two questions: (i) Do the levels of GFAP differ among these disorders? and (ii) Can GFAP be used as a biomarker for the differential diagnosis of these neurodegenerative disorders? The levels of GFAP in AD, DLB, and FTLD patients were significantly higher than those in the healthy control subjects. Although the levels of GFAP were not significantly different between AD and DLB patients, a higher level of GFAP was observed in FTLD patients than in AD and DLB patients. It is concluded that representative neurological disorders causing dementia were associated with higher levels of GFAP in the CSF. We propose the following mechanism concerning the amount of glial fibrillar acidic protein (GFAP) in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). The increase in the release of GFAP into CSF is considered to reflect the sum of degeneration of astrocytes and astrocytosis. The sum of degeneration and astrocytosis or the GFAP release could be in the order of FTLD > DLB > AD > normal condition.

  5. Apolipoprotein E genotyping and cerebrospinal fluid tau protein: implications for the clinical diagnosis of Alzheimer's disease.

    PubMed

    Arai, H; Higuchi, S; Sasaki, H

    1997-01-01

    Apolipoprotein E (ApoE) genotyping was conducted in sporadic Alzheimer's disease (AD, n = 91) as well as in other dementing disorders including Parkinson's disease (PD, n = 73), autopsy-confirmed diffuse Lewy body disease (DLBD, n = 16), progressive supranuclear palsy (n = 13), vascular dementia (n = 55), alcoholic dementia (n =25) and normal control subjects (n = 77). ApoE epsilon 4 allele frequency was significantly higher in AD (33.5%, p < 0.001), DLBD (40.6%, p < 0.001) and demented PD (29.4%, p < 0.05) compared to that in normal controls (11.7%). The association of the ApoE epsilon 4 allele with AD was more pronounced in early-onset AD (46.4%) than in late-onset AD (27.8%). 46% of the AD individuals developed AD without association to ApoE epsilon 4, and epsilon 4 homozygotes were found not only in AD, but also in many of other dementing disorders. These results suggest that ApoE genotyping cannot provide certainty about the presence of absence of AD, and that it should be used as an adjunct to other diagnostic tests for AD. On the other hand, cerebrospinal fluid (CSF) tau levels were significantly elevated (p < 0.0001) in AD (78.0 +/- 44.2 pg/ml) compared to those in normal controls (10.6 +/- 8.6 pg/ml). The specificity and the sensitivity of distinguishing AD from normal controls was 95.0 and 91.2%, respectively. Elevated CSF-tau levels were also detected in some patients with acute neurological diseases including meningoencephalitis, Creutzfeld-Jacob disease, normal pressure hydrocephalus and vitamin B12 deficiency encephalopathy. Increased CSF-tau levels in AD were found regardless of the age at onset, clinical stage, ApoE genotype, alpha 1-antichymotrypsin genotype, and presenilin-1 genotype. The CSF-tau levels continued to be abnormal during the progression of AD. These results suggest that CSF-tau serves as an unequivocal and reliable biological marker to aid in the clinical diagnosis of AD.

  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. 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.

  9. Cerebrospinal fluid lactic acidosis in bacterial meningitis.

    PubMed Central

    Eross, J; Silink, M; Dorman, D

    1981-01-01

    A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae. PMID:7294872

  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.

  11. 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

  12. 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.

  13. Quantitative analysis of human cerebrospinal fluid proteins using a combination of cysteine tagging and amine-reactive isobaric labeling.

    PubMed

    Giron, Priscille; Dayon, Loïc; Turck, Natacha; Hoogland, Christine; Sanchez, Jean-Charles

    2011-01-07

    Highly complex and dynamic protein mixtures are hardly comprehensively resolved by direct shotgun proteomic analysis. As many proteins of biological interest are of low abundance, numerous analytical methodologies have been developed to reduce sample complexity and go deeper into proteomes. The present work describes an analytical strategy to perform cysteinyl-peptide subset enrichment and relative quantification through successive cysteine and amine-isobaric tagging. A cysteine-reactive covalent capture tag (C³T) allowed derivatization of cysteines and specific isolation on a covalent capture (CC) resin. The 6-plex amine-reactive tandem mass tags (TMT) served for relative quantification of the targeted peptides. The strategy was first evaluated on a model protein mixture with increasing concentrations to assess the specificity of the enrichment and the quantitative performances of the workflow. It was then applied to human cerebrospinal fluid (CSF) from post-mortem and ante-mortem samples. These studies confirmed the specificity of the C³T and the CC technique to cysteine-containing peptides. The model protein mixture analysis showed high precision and accuracy of the quantification with coefficients of variation and mean absolute errors of less than 10% on average. The CSF experiments demonstrated the potential of the strategy to study complex biological samples and identify differential brain-related proteins. In addition, the quantification data were highly correlated with a classical TMT experiment (i.e., without C³T cysteine-tagging and enrichment steps). Altogether, these results legitimate the use of this quantitative C³T strategy to enrich and relatively quantify cysteine-containing peptides in complex mixtures.

  14. Application of an improved biuret method to the determination of total protein in urine and cerebrospinal fluid without concentration step by use of Hitachi 7170 auto-analyzer.

    PubMed

    Guobing, X; Lili, J; Lihua, Z; Tiean, X

    2001-01-01

    A biuret automated colorimetric assay for total protein in urine and cerebrospinal fluids was established. The procedures were as follows. Acidify all urine sample before analysis. Add precipitant Na(2)WO(4) to urine samples. After 10 min, centrifuge, decant the supernatant fluid, drain the inverted tubes on absorbent tissue, dissolve the precipitation with 0.1 mol/L NaOH, and finally adapt the reconstituted urine to the Hitachi 7170 analyzer. A cell-free cerebrospinal fluid sample produced by centrifugation can be inserted in an auto-analyzer for protein measurement directly. The program: mix 35 microl sample (CSF or reconstituted urine) and standard with 0.2 mol/L NaOH; incurable at 37 degrees C for 5 min, and real A1. Add concentrated biuret reagent, and 10 min later measure absorbance A2 at 546 nm vs. reagent blank. Secondary wavelength was 700 nm. The test results were calculated against a one-point standard. This biuret colorimetric method was relatively simple, fast, and accurate for the determination of protein in urine and cerebrospinal fluid, with a wide linearity extending from 0.125 g/L up to 6 g/L, had a good correlation with Benzethonium chloride turbidimetry technique, and was a practical routine method.

  15. Cerebrospinal fluid leaks following septoplasty.

    PubMed

    Venkatesan, Naren N; Mattox, Douglas E; Del Gaudio, John M

    2014-12-01

    We conducted a retrospective review to identify the characteristics of cerebrospinal fluid (CSF) leak in patients who had undergone septoplasty and in selected patients who had experienced a spontaneous CSF leak. CSF leak is a known but infrequently reported complication of septoplasty; to the best of our knowledge, only 4 cases have been previously published in the literature. A review of our institution's database revealed 3 cases of postseptoplasty CSF leak. We reviewed all the available data to look for any commonalities among these 7 cases. In addition, we reviewed 6 cases of spontaneous CSF leak selected from our database for the same purpose. For all patients, we noted the side of the cribriform plate defect, its size and, for the postseptoplasty cases, the interval between the septoplasty and the leak repair. Overall, we found that leaks were much more common on the right side than on the left. The sizes of the leaks in the 2 postseptoplasty groups were comparable (mean: 14.0 × 6.4 mm). The interval between septoplasty and leak repair ranged from 2.5 to 20 years in our cases and from 3 days to 22 weeks in the previously published cases. All 3 of the postseptoplasty patients in our database presented with clear rhinorrhea. Two of the 3 patients had meningitis; 1 of these 2 also had pneumocephalus. Of the 6 cases of spontaneous CSF leaks, 4 occurred on the right and 2 on the left; the average size of the defect was 5.8 mm in the greatest dimension. The finding that cribriform plate defects after septoplasty were typically right-sided likely reflects the prevalence of left-sided surgical approaches. Also, the fact that the defects were larger in the postseptoplasty cases than in the spontaneous cases is likely attributable to the torque effect toward the thin skull base that occurs when the perpendicular plate is twisted during septoplasty.

  16. Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity

    PubMed Central

    Morales, Diego M.; Holubkov, Richard; Inder, Terri E.; Ahn, Haejun C.; Mercer, Deanna; Rao, Rakesh; McAllister, James P.; Holtzman, David M.; Limbrick, David D.

    2015-01-01

    Background Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment. Objective The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH. Methods CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses. Results CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95). Conclusions Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant. PMID:25738507

  17. Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation.

    PubMed

    Savman, K; Nilsson, U A; Blennow, M; Kjellmer, I; Whitelaw, A

    2001-02-01

    Posthemorrhagic ventricular dilatation (PHVD) is closely associated with white matter injury and neurologic disability in the preterm infant. An important factor in periventricular white matter damage may be the specific vulnerability of iron-rich immature oligodendroglia to reactive oxygen species toxicity. Non-protein-bound iron (NPBI) is a potent catalyst in the generation of hydroxyl radicals (Fenton reaction). Our objective was to determine whether NPBI is increased in cerebrospinal fluid (CSF) from preterm infants with PHVD compared with preterm control infants. Samples of CSF were obtained from 20 infants with PHVD and 10 control subjects. The level of NPBI was determined by a new spectrophotometric method using bathophenanthroline as a chelator. To evaluate the effect of hemolysis, CSF and blood were mixed in different proportions, spun, frozen and thawed, and then analyzed for NPBI. NPBI was found in 75% (15 of 20) of infants with PHVD and in 0% (0 of 10) of control infants (p = 0.0002). Hemolysis induced in vitro did not result in any significant levels of NPBI. Within the group with PHVD, NPBI concentrations in CSF did not correlate with disability, parenchymal brain lesions, or the need for shunt surgery. NPBI was increased in CSF from preterm infants with PHVD, and the increase could not be explained by hemolysis alone. Free iron may help to explain the association between intraventricular hemorrhage and white matter damage.

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

    PubMed

    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.

  19. Cerebrospinal Fluid Biomarkers for Huntington's Disease.

    PubMed

    Byrne, Lauren M; Wild, Edward J

    2016-01-01

    Cerebrospinal fluid (CSF) is enriched in brain-derived components and represents an accessible and appealing means of interrogating the CNS milieu to study neurodegenerative diseases and identify biomarkers to facilitate the development of novel therapeutics. Many such CSF biomarkers have been proposed for Huntington's disease (HD) but none has been validated for clinical trial use. Across many studies proposing dozens of biomarker candidates, there is a notable lack of statistical power, consistency, rigor and validation. Here we review proposed CSF biomarkers including neurotransmitters, transglutaminase activity, kynurenine pathway metabolites, oxidative stress markers, inflammatory markers, neuroendocrine markers, protein markers of neuronal death, proteomic approaches and mutant huntingtin protein itself. We reflect on the need for large-scale, standardized CSF collections with detailed phenotypic data to validate and qualify much-needed CSF biomarkers for clinical trial use in HD.

  20. Comparison of Antibodies Hydrolyzing Myelin Basic Protein from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

    PubMed Central

    Doronin, Visilii B.; Parkhomenko, Taisiya A.; Castellazzi, Massimiliano; Padroni, Marina; Pastore, Michela; Buneva, Valentina N.; Granieri, Enrico; Nevinsky, Georgy A.

    2014-01-01

    It was found that antibodies (Abs) against myelin basic protein (MBP) are the major components of the antibody response in multiple sclerosis (MS) patients. We have recently shown that IgGs from sera of MS patients are active in the hydrolysis of MBP. However, in literature there are no available data concerning possible MBP-hydrolyzing Abs in cerebrospinal fluid (CSF) of MS patients. We have shown that the average content of IgGs in their sera is about 195-fold higher than that in their CSF. Here we have compared, for the first time, the average content of lambda- and kappa-IgGs as well as IgGs of four different subclasses (IgG1-IgG4) in CSF and sera of MS patients. The average relative content of lambda-IgGs and kappa –IgGs in the case of CSFs (8.0 and 92.0%) and sera (12.3 and 87.7%) are comparable, while IgG1, IgG2, IgG3, and IgG4: CSF - 40.4, 49.0, 8.2, and 2.5% of total IgGs, respectively and the sera - 53.6, 36.0, 5.6, and 4.8%, decreased in different order. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF efficiently hydrolyze MBP and that their average specific catalytic activity is unpredictably ∼54-fold higher than that of Abs from sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that anti-MBP abzymes of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. PMID:25265393

  1. Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders

    PubMed Central

    Constantinescu, Radu; Mondello, Stefania

    2013-01-01

    The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson’s disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new “omics” techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives. PMID:23346074

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

    PubMed Central

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

    2015-01-01

    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

  3. [Diagnosis of central nervous system diseases. Multivariate analysis of the serum-cerebrospinal fluid- protein relation].

    PubMed

    Neu, I S; Pelka, R B; Fateh-Moghadam, A

    1983-09-22

    In a population comprising 197 patients serum and CSF proteins were assayed using the radial immunodiffusion technique devised by Mancini. Multiple discriminant analysis was applied to investigate whether the measured CSF/serum protein relations and their ratios could be regarded as an indicator of specific neurologic diseases. One significant finding was that the slope angle alpha of the regression line between the serum/CSF relation and molecular weight may represent an important indicative parameter. A small angle is suggestive of enhanced permeability of the blood-brain barrier, a large angle of a correspondingly lowered permeability. Further, the analyses demonstrated that the combined use several predictors can markedly improve differential diagnosis. The study also demonstrates the potential of a statistical analytic technique that is still rarely applied in medicine.

  4. "Compensated hyperosmolarity" of cerebrospinal fluid and the development of hydrocephalus.

    PubMed

    Klarica, M; Miše, B; Vladić, A; Radoš, M; Orešković, D

    2013-09-17

    Acute osmolar loading of cerebrospinal fluid within one lateral ventricle of dogs was examined as a cause of water extraction from the bloodstream and an increase in intracranial pressure. We have shown that a certain amount of (3)H₂O from the bloodstream enters osmotically loaded cerebrospinal fluid significantly faster, hence causing a significant increase in intracranial pressure. The noted phenomenon in which intracranial pressure still significantly increases, but in which the hyperosmolarity of the cerebrospinal fluid is no longer present, was named "compensated hyperosmolarity". In the case of the sub-chronic application of hyperosmolar solutions into cat ventricles, we observed an increase in cerebrospinal fluid volume and a more pronounced development of hydrocephalus in the area of application, but without significant increase in intracranial pressure and without blockage of cerebrospinal fluid pathways. These results support the newly proposed hypothesis of cerebrospinal fluid hydrodynamics and the ability to develop new strategies for the treatment of cerebrospinal fluid-related diseases.

  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. Fistula detection in cerebrospinal fluid leakage1

    PubMed Central

    Allen, Marshall B.; Gammal, Taher el; Ihnen, Menard; Cowan, Morgan A.

    1972-01-01

    In two cases of cerebrospinal fluid rhinorrhoea in which scinticisternography failed to identify the fistulae, the tracts were demonstrated by positive contrast ventriculography. It is postulated that the fistula communicated with the ventricles but was isolated from the subarachnoid space by adhesions (demonstrated at operation in one case). There was `high pressure rhinorrhoea' in one case. The rhinorrhoea ceased after insertion of ventriculoatrial shunt. Images PMID:4538888

  7. 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.

  8. Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders.

    PubMed

    Zanin, Valentina; Delbue, Serena; Marcuzzi, Annalisa; Tavazzi, Eleonora; Del Savio, Rossella; Crovella, Sergio; Marchioni, Enrico; Ferrante, Pasquale; Comar, Manola

    2012-10-01

    Cytokines/chemokines are involved in the immune response of infections, including HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine patients were affected with leukoencephalopathies: five with John Cunningham virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV-not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive patients with no neurological signs (NND) and five HIV-1-negative patients affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1β, and MCP-1 were significantly higher (p < 0.05) in patients with neurological diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only TNF-β was significantly downregulated (p < 0.05) in JCV + PML patients. This pilot study emphasized the role of immunoregulation in HIV-1-related neurological disorders during cART treatment.

  9. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus

    PubMed Central

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

    2017-01-01

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

  10. Label-Free LC-MS/MS Proteomic Analysis of Cerebrospinal Fluid Identifies Protein/Pathway Alterations and Candidate Biomarkers for Amyotrophic Lateral Sclerosis.

    PubMed

    Collins, Mahlon A; An, Jiyan; Hood, Brian L; Conrads, Thomas P; Bowser, Robert P

    2015-11-06

    Analysis of the cerebrospinal fluid (CSF) proteome has proven valuable to the study of neurodegenerative disorders. To identify new protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis (ALS), we performed comparative proteomic profiling of CSF from sporadic ALS (sALS), healthy control (HC), and other neurological disease (OND) subjects using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1712 CSF proteins were detected and relatively quantified by spectral counting. Levels of several proteins with diverse biological functions were significantly altered in sALS samples. Enrichment analysis was used to link these alterations to biological pathways, which were predominantly related to inflammation, neuronal activity, and extracellular matrix regulation. We then used our CSF proteomic profiles to create a support vector machines classifier capable of discriminating training set ALS from non-ALS (HC and OND) samples. Four classifier proteins, WD repeat-containing protein 63, amyloid-like protein 1, SPARC-like protein 1, and cell adhesion molecule 3, were identified by feature selection and externally validated. The resultant classifier distinguished ALS from non-ALS samples with 83% sensitivity and 100% specificity in an independent test set. Collectively, our results illustrate the utility of CSF proteomic profiling for identifying ALS protein/pathway alterations and candidate disease biomarkers.

  11. CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE

    PubMed Central

    Whedon, James M.; Glassey, Donald

    2010-01-01

    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 breathwork, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted. PMID:19472865

  12. 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.

  13. [Cerebrospinal fluid biomarkers for the early diagnosis of Parkinson's disease].

    PubMed

    da Costa, Andreia Gomes; Gago, Miguel Fernandes; Garrett, Carolina

    2011-12-01

    In current medical practice, the diagnosis of Parkinson's disease remains essentially clinical. This practice determines that the diagnosis of Parkinson's disease is done in an already advanced neuropathological stage of the disease. The aim of this study is to review the validity of cerebrospinal fluid protein biological markers in the early diagnosis of Parkinson's disease. The a-synuclein and DJ-1 proteins, due to their role in the hereditary Parkinson's disease, have been the most widely studied cerebrospinal biomarkers. Nevertheless, they have had divergent results mostly owing to different processing, identification and control of laboratory techniques. The new proteomic techniques, directed to the detection of multiple undifferentiated proteins in cerebrospinal fluid (eg. ceruloplasmin, chromogranin B, apoH), are promising. The early diagnosis of Parkinson's disease is imperious as it is a progressive neurodegenerative disorder that causes extensive morbidity. Most of current scientific research in Parkinson's disease is focused on the discovery of neuroprotective drugs. Thus, the definition of biomarkers for the early diagnosis of Parkinson's disease is highly relevant.

  14. Drug transport in brain via the cerebrospinal fluid

    PubMed Central

    2011-01-01

    The human brain has no lymphatic system, but produces over a half-liter each day of cerebrospinal fluid. The cerebrospinal fluid is secreted at the choroid plexus and occupies the cavities of the four ventricles, as well as the cranial and spinal sub-arachnoid space. The cerebrospinal fluid moves over the surfaces of the brain and spinal cord and is rapidly absorbed into the general circulation. The choroid plexus forms the blood-cerebrospinal fluid barrier, and this barrier is functionally distinct from the brain microvascular endothelium, which forms the blood-brain barrier. Virtually all non-cellular substances in blood distribute into cerebrospinal fluid, and drug entry into cerebrospinal fluid is not an index of drug transport across the blood-brain barrier. Drug injected into the cerebrospinal fluid rapidly moves into the blood via bulk flow, but penetrates into brain tissue poorly owing to the limitations of diffusion. Drug transport into cerebrospinal fluid vs. brain interstitial fluid requires knowledge of the relative expression of transporters at the choroid plexus versus the brain microvascular endothelium. PMID:21349155

  15. 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

  16. Cerebrospinal Fluid Levels of Leptin, Proopiomelanocortin, and Agouti-Related Protein in Human Pregnancy: Evidence for Leptin Resistance

    PubMed Central

    Page-Wilson, Gabrielle; Reitman-Ivashkov, Elena; Meece, Kana; White, Anne; Rosenbaum, Michael; Smiley, Richard M.

    2013-01-01

    Context: Leptin suppresses appetite by modulating the expression of hypothalamic neuropeptides including proopiomelanocortin (POMC) and agouti-related peptide (AgRP). Yet during pregnancy, caloric consumption increases despite elevated plasma leptin levels. Design and Participants: To investigate this paradox, we measured leptin and soluble leptin receptor in plasma and leptin, POMC, and AgRP in cerebrospinal fluid (CSF) from 21 fasting pregnant women before delivery by cesarean section at a university hospital and from 14 fasting nonpregnant women. Results: Prepregnancy body mass index was 24.6 ± 1.1 (se) vs. 31.3 ± 1.3 at term vs. 26.5 ± 1.6 kg/m2 in controls. Plasma leptin (32.9 ± 4.6 vs. 16.7 ± 3.0 ng/ml) and soluble leptin receptor (30.9 ± 2.3 vs. 22.1 ± 1.4 ng/ml) levels were significantly higher in pregnant women. However, mean CSF leptin did not differ between the two groups (283 ± 34 vs. 311 ± 32 pg/ml), consistent with a relative decrease in leptin transport into CSF during pregnancy. Accordingly, the CSF/plasma leptin percentage was 1.0 ± 0.01% in pregnant subjects vs. 2.1 ± 0.2% in controls (P < 0.0001). Mean CSF AgRP was significantly higher in pregnant subjects (32.3 ± 2.7 vs. 23.5 ± 2.5 pg/ml; P = 0.03). Mean CSF POMC was not significantly different in pregnant subjects (200 ± 13.6 vs. 229 ± 17.3 fmol/ml; P = 0.190). However, the mean AgRP/POMC ratio was significantly higher among pregnant women (P = 0.003), consistent with an overall decrease in melanocortin tone favoring increased food intake during pregnancy. Conclusions: These data demonstrate that despite peripheral hyperleptinemia, positive energy balance is achieved during pregnancy by a relative decrease in central leptin concentrations and resistance to leptin's effects on target neuropeptides that regulate energy balance. PMID:23118421

  17. Diagnostic value of circulating tumor cells in cerebrospinal fluid

    PubMed Central

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

    2016-01-01

    Abstract Objective To assess circulating tumor cells in cerebrospinal fluid as a diagnostic approach to identify meningeal metastasis in patients with non-small cell lung cancer by using tumor marker immunostaining–fluorescence in situ hybridization (TM-iFISH). Methods In 5 non-small cell lung cancer patients who were confirmed to have developed meningeal metastasis by cerebrospinal fluid cytology, 20 ml of cerebrospinal fluid was obtained through lumbar puncture, from which 7.5 ml was utilized for TM-iFISH to identify and quantitate circulating tumor cells, 10ml for cerebrospinal fluid cytology, and 2.5ml for detection of cerebrospinal fluid tumor markers. Results TM-iFISH examination identified 18 to 1,823 circulating tumor cells per 7.5ml cerebrospinal fluid. In contrast, cytology assessment revealed tumor cells in only 2 cases. The expression levels of cerebrospinal fluid tumor markers were all increased in all 5 patients when compared with their respective serum levels. Contrast-enhanced MRI scans demonstrated presence of meningeal metastasis in all 5 cases. Conclusion TM-iFISH may become a novel cerebrospinal fluid-based diagnostic strategy to identify circulating tumor cells and meningeal metastasis as compared to traditional diagnostic approaches, although its superior sensitivity and specificity needs to be confirmed through additional studies with a larger sample size.

  18. Volumetric relief map for intracranial cerebrospinal fluid distribution analysis.

    PubMed

    Lebret, Alain; Kenmochi, Yukiko; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe; Petit, Éric

    2015-09-01

    Cerebrospinal fluid imaging plays a significant role in the clinical diagnosis of brain disorders, such as hydrocephalus and Alzheimer's disease. While three-dimensional images of cerebrospinal fluid are very detailed, the complex structures they contain can be time-consuming and laborious to interpret. This paper presents a simple technique that represents the intracranial cerebrospinal fluid distribution as a two-dimensional image in such a way that the total fluid volume is preserved. We call this a volumetric relief map, and show its effectiveness in a characterization and analysis of fluid distributions and networks in hydrocephalus patients and healthy adults.

  19. 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

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

    PubMed

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

    2017-03-28

    Cutaneous fistula of cerebrospinal fluid is a rare complication of neuroaxial blockade. We report the case of a parturient in whom an epidural catheter was placed for labour analgesia and 12h after the catheter was removed, presented an abundant asymptomatic fluid leak from the puncture site, compatible in the cyto-chemical analysis with cerebrospinal fluid. She was treated with acetazolamide, compression of skin orifice of the fluid leakage, antibiotic prophylaxis, hydration and rest, and progressed satisfactorily without requiring blood patch.

  1. Elevated cerebrospinal fluid tau in Wernicke encephalopathy.

    PubMed

    Frijlink, Daphne W; Tilanus, Joachim J; Roks, Gerwin

    2012-08-08

    Wernicke encephalopathy (WE) commonly presents with oculomotor abnormalities, gait ataxia and confusion. WE can mimic rapidly progressive dementia syndromes, such as Creutzfeldt-Jakob disease (CJD). Cerebrospinal fluid (CSF) tau is frequently used for diagnosis of several dementia subtypes, predominantly CJD and Alzheimer's disease. The combination of very high CSF tau (tau) and normal phosphorylated tau (p-tau) levels is almost exclusively seen in aggressive diseases, such as CJD. The authors present a case of a woman with WE, caused by chronic insufficient dietary intake, with highly elevated CSF tau and normal p-tau. The clinical symptoms and CSF findings raised the suspicion of CJD. However, shortly after immediate treatment with thiamine the patient clinically improved. At follow-up, 2.5 months later, she had made a good recovery. This case of rapidly progressive dementia illustrates that, even in the case of a highly elevated CSF tau, clinicians should be alert for treatable causes such as WE.

  2. 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

  3. 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.

  4. Minimally invasive neurosurgery for cerebrospinal fluid disorders.

    PubMed

    Guillaume, Daniel J

    2010-10-01

    This article focuses on minimally invasive approaches used to address disorders of cerebrospinal fluid (CSF) circulation. The author covers the primary CSF disorders that are amenable to minimally invasive treatment, including aqueductal stenosis, fourth ventricular outlet obstruction (including Chiari malformation), isolated lateral ventricle, isolated fourth ventricle, multiloculated hydrocephalus, arachnoid cysts, and tumors that block CSF flow. General approaches to evaluating disorders of CSF circulation, including detailed imaging studies, are discussed. Approaches to minimally invasive management of such disorders are described in general, and for each specific entity. For each procedure, indications, surgical technique, and known outcomes are detailed. Specific complications as well as strategies for their avoidance and management are addressed. Lastly, future directions and the need for structured outcome studies are discussed.

  5. 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

  6. 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

  7. Secretion of laminin alpha 2 chain in cerebrospinal fluid.

    PubMed

    Yamada, H; Hori, H; Tanaka, T; Fujita, S; Fukuta-Ohi, H; Hojo, S; Tamura, A; Shimizu, T; Matsumura, K

    1995-11-27

    The absence of laminin alpha 2 chain causes muscle cell degeneration and peripheral dysmyelination in congenital muscular dystrophy patients and dy mice, suggesting its role in the maintenance of sarcolemmal architecture and peripheral myelinogenesis. Here we demonstrate the secretion of laminin alpha 2 chain in cerebrospinal fluid (CSF). Laminin alpha 2 chain was detected as a minor component of the total CSF proteins or glycoproteins. Laminin alpha 2 chain was localized in the cytoplasm of epithelial cells of choroid plexus, suggesting active secretion. Our results suggest that immunochemical analysis of CSF laminin alpha 2 chain could be useful as an aid for the diagnosis of congenital muscular dystrophy.

  8. Electrophoresis-tutor: an image-based personal computer program that teaches clinical interpretation of protein electrophoresis patterns of serum, urine, and cerebrospinal fluid.

    PubMed

    Astion, M L; Rank, J; Wener, M H; Torvik, P; Schneider, J B; Killingsworth, L M

    1995-09-01

    High-resolution protein electrophoresis of serum, urine, and cerebrospinal fluid (CSF) can aid in the diagnosis of multiple myeloma, amyloidosis, macroglobulinemia, multiple sclerosis, and other diseases. Electrophoresis-Tutor is a personal computer program based on approximately 150 digital images that teaches the clinical interpretation of agarose gel electrophoretic patterns. The program is divided into the following sections: introduction, CSF, serum, urine, review of disease states, program navigator, and final exam. The CSF section describes normal and abnormal CSF findings with emphasis on oligoclonal banding, as seen in the CSF of patients with multiple sclerosis. The serum section emphasizes monoclonal gammopathy patterns but also has detailed descriptions of inflammation, liver disease, protein-losing disorders, genetic deficiencies, and other patterns. Monoclonal gammopathy is described in the context of specific associated clinical conditions (e.g., myeloma, amyloidosis). For each monoclonal gammopathy example, results of standard electrophoresis, densitometry, and immunofixation are presented. The review of disease states uses animation to illustrate the development and remission of a variety of pathological patterns. The program navigator allows the user to jump quickly to any place in the program. The optional exam contains 20 questions, and detailed feedback is given after each question. Electrophoresis-Tutor can be used as a stand-alone teaching tool, a companion to traditional instruction, or a reference source.

  9. Quantitative evaluation fo cerebrospinal fluid shunt flow

    SciTech Connect

    Chervu, S.; Chervu, L.R.; Vallabhajosyula, B.; Milstein, D.M.; Shapiro, K.M.; Shulman, K.; Blaufox, M.D.

    1984-01-01

    The authors describe a rigorous method for measuring the flow of cerebrospinal fluid (CSF) in shunt circuits implanted for the relief of obstructive hydrocephalus. Clearance of radioactivity for several calibrated flow rates was determined with a Harvard infusion pump by injecting the Rickham reservoir of a Rickham-Holter valve system with 100 ..mu..Ci of Tc-99m as pertechnetate. The elliptical and the cylindrical Holter valves used as adjunct valves with the Rickham reservoir yielded two different regression lines when the clearances were plotted against flow rats. The experimental regression lines were used to determine the in vivo flow rates from clearances calculated after injecting the Rickham reservoirs of the patients. The unique clearance characteristics of the individual shunt systems available requires that calibration curves be derived for an entire system identical to one implanted in the patient being evaluated, rather than just the injected chamber. Excellent correlation between flow rates and the clinical findings supports the reliability of this method of quantification of CSF shunt flow, and the results are fully accepted by neurosurgeons.

  10. Doxepin concentrations in plasma and cerebrospinal fluid.

    PubMed

    Schomburg, Robert; Remane, Daniela; Fassbender, Klaus; Maurer, Hans H; Spiegel, Jörg

    2011-04-01

    Doxepin--like other antidepressant drugs (ADs)--shows a variable antidepressant effect in clinical practice. The cause for this variability is as yet unclear; however, pharmacokinetic factors such as the variable permeability of doxepin into the cerebrospinal fluid (CSF), may contribute to the difference in therapeutic efficacy. We measured and correlated the concentration of doxepin and its active metabolite nordoxepin in both the plasma and CSF. Plasma and CSF samples were taken simultaneously from 21 patients who were treated with doxepin due to different clinical indications. The plasma concentration of both doxepin and nordoxepin correlated significantly with the oral dosage of doxepin (doxepin: r = +0.66, p < 0.001; nordoxepin: r = +0.78, p < 0.0001; Spearman's correlation). Furthermore, we found significant correlations between the plasma and CSF concentrations of both doxepin (r = +0.71; p < 0.001; Pearson's correlation) and nordoxepin (r = +0.74; p < 0.001). These highly significant correlations between the plasma and CSF concentrations indicate a constant CSF permeability of doxepin and its active metabolite nordoxepin.

  11. 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.

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

    PubMed

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

    2017-01-01

    Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments. Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid, associated with the pathophysiology or pathogenesis of PD. This systematic review includes cerebrospinal fluid biomarker studies focusing on different disease pathways: oxidative stress, neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3) severity of disease (motor symptoms) and (4) cognitive dysfunction. Oligomeric alpha-synuclein might be helpful in the separation of PD from controls. Through metabolomics, changes in purine and tryptophan metabolism have been discovered in patients with PD. Neurofilament light chain (NfL) has a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau-proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD. In the future, larger longitudinal studies, corroborating previous research on viable biomarker candidates or using metabolomics identifying a vast amount of potential biomarkers, could be a good approach.

  13. 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

  14. Use of Z310 Cells as an In Vitro Blood-Cerebrospinal Fluid Barrier Model: Tight Junction Proteins and Transport Properties

    PubMed Central

    Shi, Lewis Zhichang; Li, G. Jane; Wang, Shunzhen; Zheng, Wei

    2009-01-01

    Immortalized rat choroidal epithelial Z310 cells have the potential to become an in vitro model for studying transport of materials at blood-cerebrospinal fluid barrier (BCB) (Shi and Zheng, Brain Research 1057:37-48, 2005). This study was designed to demonstrate the presence of tight junction properties in Z310 cells and the functionality of Z310 monolayer in transport of selected model compounds. Western blot analyses revealed the presence of claudin-1, ZO-1, and occludin in Z310 cells. Transmission electron microscopy showed a “tight junction” type of structure in the sub-apical lateral membranes between adjacent Z310 cells. Real-time RT-PCR revealed that Z310 cells expressed representative transporters such as DMT1, MTP1, TfR, p-glycoprotein, ATP7A, ZnT1, ABCC1, Oat3, OCT1 and OB-Ra. Moreover, Z310 cells cultured in a two-chamber Transwell device possessed the ability to transport zidovudine (anionic drug), thyroxine (hormone), thymidine (nucleoside), and leptin (large polypeptide) with kinetic properties similar to those obtained from the in vitro model based on primary culture of choroidal epithelial cells. Taken together, these data indicate that the Z310 BCB model expresses major tight junction proteins and forms a tight barrier in vitro. The model also exhibits the ability to transport substances of various categories across the barrier. PMID:17825520

  15. 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

  16. Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid β-peptides in human cerebrospinal fluid

    PubMed Central

    Halim, Adnan; Brinkmalm, Gunnar; Rüetschi, Ulla; Westman-Brinkmalm, Ann; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Larson, Göran; Nilsson, Jonas

    2011-01-01

    The proteolytic processing of human amyloid precursor protein (APP) into shorter aggregating amyloid β (Aβ)-peptides, e.g., Aβ1-42, is considered a critical step in the pathogenesis of Alzheimer’s disease (AD). Although APP is a well-known membrane glycoprotein carrying both N- and O-glycans, nothing is known about the occurrence of released APP/Aβ glycopeptides in cerebrospinal fluid (CSF). We used the 6E10 antibody and immunopurified Aβ peptides and glycopeptides from CSF samples and then liquid chromatography—tandem mass spectrometry for structural analysis using collision-induced dissociation and electron capture dissociation. In addition to 33 unglycosylated APP/Aβ peptides, we identified 37 APP/Aβ glycopeptides with sialylated core 1 like O-glycans attached to Thr(−39, −21, −20, and −13), in a series of APP/AβX-15 glycopeptides, where X was −63, −57, −52, and −45, in relation to Asp1 of the Aβ sequence. Unexpectedly, we also identified a series of 27 glycopeptides, the Aβ1-X series, where X was 20 (DAEFRHDSGYEVHHQKLVFF), 19, 18, 17, 16, and 15, which were all uniquely glycosylated on Tyr10. The Tyr10 linked O-glycans were (Neu5Ac)1-2Hex(Neu5Ac)HexNAc-O- structures with the disialylated terminals occasionally O-acetylated or lactonized, indicating a terminal Neu5Acα2,8Neu5Ac linkage. We could not detect any glycosylation of the Aβ1-38/40/42 isoforms. We observed an increase of up to 2.5 times of Tyr10 glycosylated Aβ peptides in CSF in six AD patients compared to seven non-AD patients. APP/Aβ sialylated O-glycans, including that of a Tyr residue, the first in a mammalian protein, may modulate APP processing, inhibiting the amyloidogenic pathway associated with AD. PMID:21712440

  17. Predictive Value of Cerebrospinal Fluid Visinin-Like Protein-1 Levels for Alzheimer's Disease Early Detection and Differential Diagnosis in Patients with Mild Cognitive Impairment.

    PubMed

    Babić Leko, Mirjana; Borovečki, Fran; Dejanović, Nenad; Hof, Patrick R; Šimić, Goran

    2016-01-01

    Visinin-like protein 1 (VILIP-1) recently emerged as a potential biomarker of Alzheimer's disease (AD). This neuronal calcium sensor protein previously used as a marker of acute ischemic stroke is elevated in the cerebrospinal fluid (CSF) of AD patients. The goal of this study was to assess CSF VILIP-1 potential in early AD diagnosis and in differentiating mild cognitive impairment (MCI) patients with and without risk of AD. Additionally, we tested VILIP-1 ability to differentiate AD from other primary causes of dementia, and predict the progression of AD-related cognitive decline. VILIP-1 levels were compared with five CSF AD biomarkers (t-tau, Aβ1-42, p-tau181, p-tau199, and p-tau231). VILIP-1 successfully differentiated two MCI patient groups characterized by absence or presence of pathological levels of these CSF biomarkers, except for t-tau. VILIP-1/Aβ(1-42) and VILIP-1/p-tau181 ratios also differentiated MCI patients with pathological CSF biomarker levels. However, there was no difference in VILIP-1 levels between AD and MCI patients. VILIP-1/Aβ(1-42) and VILIP-1/p-tau231 ratios reached high sensitivities (above 70%) and very high specificities (above 85%) in differentiating AD patients from HC. Additionally, VILIP-1 differentiated AD from patients with Lewy body disease with 77.1% sensitivity and 100% specificity. VILIP-1 potential as a prognostic biomarker of cognitive decline in AD was also proved since VILIP-1/t-tau, VILIP-1/p-tau181, and VILIP-1/p-tau231 ratios correlated with MMSE scores. These data indicate that VILIP-1 alone or in combination with other AD CSF biomarkers represent a valuable marker for the early diagnosis of AD, recognition of MCI patients at higher risk to develop dementia, and in differentiating AD from LBD.

  18. 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

  19. 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

  20. 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

  1. A new sandwich immunoassay for detection of the α-secretase cleaved, soluble amyloid-β protein precursor in cerebrospinal fluid and serum.

    PubMed

    Taverna, Mara; Straub, Tobias; Hampel, Harald; Rujescu, Dan; Lichtenthaler, Stefan F

    2013-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder. Frequently used diagnostic biomarkers are amyloid-β42 (Aβ42), tau, and phospho-tau, which are measured in cerebrospinal fluid (CSF), and allow a reasonable, but not full, separation of AD patients and controls. Besides Aβ42, additional proteolytic cleavage products of the amyloid-β protein precursor (AβPP) have been investigated as potential biomarkers. This includes the α-secretase cleaved soluble AβPP ectodomain (sAβPPα). However, some studies found a reduction of sAβPPα, whereas other studies reported an increase of sAβPPα in the CSF of AD patients. The divergent findings may result from the detection of sAβPPα with antibodies, such as 6E10, which do not exclusively detect sAβPPα, but also the alternative β-secretase cleavage product sAβPPβ'. Here, we used the sAβPPα-specific antibody 14D6 and developed an ELISA-like sandwich immunoassay. The assay specifically detected sAβPPα in cell culture supernatants, in human CSF and even in serum, which is more readily accessible than CSF. The assay was used to analyze sAβPPα levels in CSF and serum of AD patients and controls. The assay detected a mild, but significant increase in sAβPPα in the CSF of AD patients compared to non-demented controls, while a mild reduction was observed in serum. The 14D6 assay in CSF allowed a better separation of AD patients from controls compared to the 6E10 antibody. Taken together, the new assay is widely applicable for specific sAβPPα measurement in culture media, CSF, and serum.

  2. Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma and cerebrospinal fluid, followed by high-performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Xue, Y J; Pursley, Janice; Arnold, Mark

    2007-04-11

    BMS-299897 is a gamma-secretase inhibitor that is being developed for the treatment of Alzheimer's disease. Liquid-liquid extraction (LLE), chromatographic/tandem mass spectrometry (LC/MS/MS) methods have been developed and validated for the quantitation of BMS-299897 in human plasma and cerebrospinal fluid (CSF). Both methods utilized (13)C6-BMS-299897, the stable label isotope analog, as the internal standard. For the human plasma extraction method, two incubation steps were required after the addition of 5 mM ammonium acetate and the internal standard in acetonitrile to release the analyte bound to proteins prior to LLE with toluene. For the human CSF extraction method, after the addition of 0.5 N HCl and the internal standard, CSF samples were extracted with toluene and no incubation was required. The organic layers obtained from both extraction methods were removed and evaporated to dryness. The residues were reconstituted and injected into the LC/MS/MS system. Chromatographic separation was achieved isocratically on a MetaChem C18 Hypersil BDS column (2.0 mm x 50 mm, 3 microm). The mobile phase contained 10 mM ammonium acetate pH 5 and acetonitrile. Detection was by negative ion electrospray tandem mass spectrometry. The standard curves ranged from 1 to 1000 ng/ml for human plasma and 0.25-100 ng/ml for human CSF. Both standard curves were fitted to a 1/x weighted quadratic regression model. For both methods, the intra-assay precision was within 8.2% CV, the inter-assay precision was within 5.4% CV, and assay accuracy was within +/-7.4% of the nominal values. The validation and sample analysis results demonstrated that both methods had acceptable precision and accuracy across the calibration ranges.

  3. 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

  4. Cerebrospinal fluid oligoclonal bands in childhood opsoclonus-myoclonus.

    PubMed

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

    2011-07-01

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

  5. Cerebral microbleeds topography and cerebrospinal fluid biomarkers in cognitive impairment.

    PubMed

    Shams, Sara; Granberg, Tobias; Martola, Juha; Charidimou, Andreas; Li, Xiaozhen; Shams, Mana; Fereshtehnejad, Seyed-Mohammad; Cavallin, Lena; Aspelin, Peter; Wiberg-Kristoffersen, Maria; Wahlund, Lars-Olof

    2017-03-01

    Cerebral microbleeds, a marker of small vessel disease, are thought to be of importance in cognitive impairment. We aimed to study topographical distribution of cerebral microbleeds, and their involvement in disease pathophysiology, reflected by cerebrospinal fluid biomarkers; 1039 patients undergoing memory investigation underwent lumbar puncture and a brain magnetic resonance imaging scan. Cerebrospinal fluid samples were analyzed for amyloid β(Aβ)42, total tau(T-tau), tau phosphorylated at threonine 18(P-tau) and cerebrospinal fluid/serum albumin ratios. Magnetic resonance imaging sequences were evaluated for small vessel disease markers, including cerebral microbleeds, white matter hyperintensities and lacunes. Low Aβ42 levels were associated with lobar cerebral microbleeds in the whole cohort and Alzheimer's disease ( P < 0.001). High cerebrospinal fluid/serum albumin ratios were seen with increased number of cerebral microbleeds in the brainstem ( P < 0.001). There were tendencies for increased Aβ42 levels and decreased Tau levels with deep and infratentorial cerebral microbleeds ( P < 0.05). Lobar cerebral microbleeds were associated with white matter hyperintensities and lacunes ( P < 0.001). Probable cerebral amyloid angiopathy-related cerebral microbleeds were associated with low Aβ42 levels and lacunes, whereas probable cerebral amyloid angiopathy-unrelated cerebral microbleeds were associated with white matter hyperintensities ( P < 0.001). Our findings show that cerebral microbleed distribution is associated with different patterns of cerebrospinal fluid biomarkers, supporting different pathogenesis of deep/infratentorial and lobar cerebral microbleeds.

  6. 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.

  7. Peptidome Analysis of Cerebrospinal Fluid by LC-MALDI MS

    PubMed Central

    Hölttä, Mikko; Zetterberg, Henrik; Mirgorodskaya, Ekaterina; Mattsson, Niklas; Blennow, Kaj; Gobom, Johan

    2012-01-01

    We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000–4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders. PMID:22880031

  8. 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

  9. Observations on vitamin B12 in serum and cerebrospinal fluid in multiple sclerosis

    PubMed Central

    Basil, W.; Brown, J. K.; Matthews, D. M.

    1965-01-01

    There are several claims that B12 concentrations in serum and cerebrospinal fluid are grossly abnormal in multiple sclerosis, but results are conflicting. This paper reports measurements of these concentrations in 40 serum samples and 23 samples of lumbar cerebrospinal fluid from cases of multiple sclerosis, and in appropriate controls, using Euglena gracilis, z strain. The serum concentrations were found to be normal; the mean concentration in cerebrospinal fluid was slightly reduced, but all values were within the control range. In both control samples and samples from cases of multiple sclerosis, the B12 concentration in lumbar cerebrospinal fluid was correlated with the concentration in serum. There was no correlation between B12 concentration and total protein in cerebrospinal fluid. A number of estimations of serum B12 were also made with Lactobacillus leichmannii, after extraction in the presence and absence of cyanide. These showed a difference between cases of multiple sclerosis and controls, one interpretation of which might be that the serum in multiple sclerosis contains an abnormally low concentration of hydroxocobalamin. PMID:14304244

  10. 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.

  11. 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

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

    PubMed

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

    2013-12-01

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

  13. Coccidioides immitis presenting as a hyphal form in cerebrospinal fluid.

    PubMed Central

    Zepeda, M. R.; Kobayashi, G. K.; Appleman, M. D.; Navarro, A.

    1998-01-01

    This article reports a case of Coccidioides immitis that presented as a hyphal form in a 38-year-old patient. The organism was observed growing exclusively as hyphae in the cerebrospinal fluid by microscopic examination. Coccidioides immitis was the only organism cultured. The identification of C immitis was confirmed by both standard culture methods and DNA probe studies. Images Figure PMID:9685779

  14. Closure of cerebrospinal fluid leakage after transsphenoidal surgery: technical note.

    PubMed

    Freidberg, S R; Hybels, R L; Bohigian, R K

    1994-07-01

    It is necessary to pack the sella turcica to prevent the leakage of cerebrospinal fluid after transsphenoidal surgery if the arachnoid has been torn. The packing is usually supported by nasal cartilage. If this is not available, we recommend the Synthes minifragment plate to support the intradural pack.

  15. Entamoeba histolytica meningoencephalitis diagnosed by trophozoites in cerebrospinal fluid

    PubMed Central

    Goh, L M L; Marrone, J R

    2013-01-01

    Entamoeba histolytica meningoencephalitis has not been described in the modern literature, which is distinct from that caused by free-living amoebae. We report the first case of E. histolytica meningoencephalitis without liver or brain abscesses. Cerebrospinal fluid revealed 2 + very motile trophozoites. Our patient was successfully treated with intravenous metronidazole. PMID:25356319

  16. Entamoeba histolytica meningoencephalitis diagnosed by trophozoites in cerebrospinal fluid.

    PubMed

    Goh, L M L; Marrone, J R

    2013-10-01

    Entamoeba histolytica meningoencephalitis has not been described in the modern literature, which is distinct from that caused by free-living amoebae. We report the first case of E. histolytica meningoencephalitis without liver or brain abscesses. Cerebrospinal fluid revealed 2 + very motile trophozoites. Our patient was successfully treated with intravenous metronidazole.

  17. Effect of cerebrospinal fluid shunts on intracranial pressure and on cerebrospinal fluid dynamics

    PubMed Central

    Fox, John L.; McCullough, David C.; Green, Robert C.

    1973-01-01

    Part 2 describes measurements of intracranial cerebrospinal fluid (CSF) pressure in 18 adult patients with CSF shunts, all pressure measurements being referred to a horizontal plane close to the foramina of Monro. All 18 patients had normal CSF pressure by lumbar puncture; however, in one patient an intracranial pressure of +280 mm was subsequently measured after pneumoencephalography. Twelve patients had pre-shunt CSF pressures measured intracranially: 11 ranged from +20 to +180 mm H2O and one was +280 mm H2O in the supine position. In the upright posture nine patients had values of −10 to −140 mm H2O, while three others were +60, +70, and +280 mm H2O. After CSF shunting in these 18 patients the pressures were −30 to +30 mm H2O in the supine position and −210 to −370 mm in the upright position. The effect of posture on the siphoning action of these longer shunts in the erect, adult patient is a major uncontrollable variable in maintenance of intracranial pressure after shunting. Other significant variables are reviewed. In Part 3 a concept of the hydrocephalus phenomenon is described. Emphasis is placed on the pressure differential (Pd) and force differential (Fd) causing pre-shunt ventricular enlargement and post-shunt ventricular size reduction. The site of Pd, which must be very small and not to be confused with measured ventricular pressure, P, must be at the ventricular wall. Images PMID:4541079

  18. 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)

  19. Differential proteomics analysis of mononuclear cells in cerebrospinal fluid of Parkinson's disease.

    PubMed

    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.

  20. Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease

    PubMed Central

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

    2014-01-01

    During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12). The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution. PMID:24695528

  1. 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

  2. Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

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

    2011-01-01

    The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, Aβ42, NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-α concentration was low in iNPH patients. PMID:21660204

  3. Diagnostic value of creatine kinase activity in canine cerebrospinal fluid

    PubMed Central

    Ferreira, Alexandra

    2016-01-01

    This study aimed to determine whether creatine kinase (CK) activity in cerebrospinal fluid (CSF) has diagnostic value for various groups of neurological conditions or for different anatomical areas of the nervous system (NS). The age, breed, results of CSF analysis, and diagnosis of 578 canine patients presenting with various neurological conditions between January 2009 and February 2015 were retrospectively collected. The cases were divided according to anatomical areas of the nervous system, i.e., brain, spinal cord, and peripheral nervous system, and into groups according to the nature of the condition diagnosed: vascular, immune/inflammatory/infectious, traumatic, toxic, anomalous, metabolic, idiopathic, neoplastic, and degenerative. Statistical analysis showed that CSF-CK alone cannot be used as a diagnostic tool and that total proteins in the CSF and red blood cells (RBCs) do not have a significant relationship with the CSF-CK activity. CSF-CK did not have a diagnostic value for different disease groups or anatomical areas of the nervous system. PMID:27708448

  4. Evaluation of cytospin precision in low cellularity canine cerebrospinal fluid.

    PubMed

    Krimer, Paula M; Haley, Allison C; Harvey, Stephen B; Schatzberg, Scott J

    2016-03-01

    The cell count and differential of cerebrospinal fluid (CSF) cytologic examination classify CSF as inflammatory or not. The cytospin cell yield is related to cell count, but to our knowledge a relationship has not been characterized and cytospin precision is undocumented in any species. The objective of our study was to calculate intra-assay precision of cellular yield and differential on cytocentrifuged canine CSF, determine the factors that may affect precision, and predict the number of cytospins necessary to confirm mild neutrophilic pleocytosis. Ten concurrent replicate cytospins were created from nonhemorrhagic CSF, obtained from 60 dogs in other terminal studies, with either a manual or calibrated pipetting technique. Up to 500 cells per cytospin were counted and classified on each slide. Coefficient of variation (CV), multiple regression, and probabilities were calculated for relationships between cell yield and independent factors including technique, total nucleated cell count, cell differential, and total protein. Manual and calibrated pipetting had similar CVs (average 31%) for total cell yield, but the calibrated technique had fewer foamy macrophages. CV for neutrophil percentage among low cellularity samples with any neutrophils was 146%. Probability based on linear regression showed that 1 cytospin is sufficient to identify samples with >3% neutrophils. Occasional neutrophils, eosinophils, mitotic figures, phagocytic cells, and ependymal cells were seen in many low cellularity canine CSF samples. Canine CSF cytospin cell yield and differential evaluations are imprecise. Calibrated rather than manual pipetting is recommended.

  5. Cerebrospinal Fluid Dynamics and the Pathophysiology of Hydrocephalus: New Concepts.

    PubMed

    Yamada, Shinya; Kelly, Erin

    2016-04-01

    Many controversies remain regarding basic cerebrospinal fluid (CSF) physiology and the mechanism behind the development of hydrocephalus. Recent information obtained from CSF time spatial spin labeling inversion pulse method discovers different aspect of CSF dynamics. In this article, we would discuss how recent CSF imaging advances are leading to new concepts of CSF flow dynamics and the pathophysiology of hydrocephalus, with an emphasis on time spatial spin labeling inversion pulse imaging of CSF dynamics.

  6. Cerebrospinal fluid involvement in acute promyelocytic leukaemia at presentation

    PubMed Central

    Mishra, Jyoti; Gupta, Mayank

    2015-01-01

    In acute promyelocytic leukaemia (APL), extramedullary disease (EMD) is rare but can occur in those who relapse following therapy. Although the most common site of EMD in APL is central nervous system (CNS) and skin, CNS involvement in recently diagnosed patients with APL is very rare and rarely described. We report cerebrospinal fluid involvement in a case of APL, on day 3 of induction therapy. PMID:25754165

  7. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease.

    PubMed

    Hong, Zhen; Shi, Min; Chung, Kathryn A; Quinn, Joseph F; Peskind, Elaine R; Galasko, Douglas; Jankovic, Joseph; Zabetian, Cyrus P; Leverenz, James B; Baird, Geoffrey; Montine, Thomas J; Hancock, Aneeka M; Hwang, Hyejin; Pan, Catherine; Bradner, Joshua; Kang, Un J; Jensen, Poul H; Zhang, Jing

    2010-03-01

    Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and alpha-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy individuals and 50 patients with Alzheimer's disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in Parkinson's patients versus controls or Alzheimer's patients when blood contamination was controlled for. In the population aged > or = 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein, respectively, the sensitivity and specificity for patients with Parkinson's disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or alpha-synuclein and the severity of Parkinson's disease. Taken together, this represents

  8. Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma*

    PubMed Central

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

    2012-01-01

    Cerebrospinal fluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinal fluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the identification of biomarkers and classification of neurological diseases. PMID:22240505

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

    PubMed

    Cökeliler, D; Caner, H; Zemek, J; Choukourov, A; Biederman, H; Mutlu, M

    2007-03-01

    Prosthetic devices, mainly shunts, are frequently used for temporary or permanent drainage of cerebrospinal fluid. The pathogenesis of shunt infection is a very important problem in modern medicine and generally this is characterized by staphylococcal adhesion to the cerebrospinal fluid shunt surfaces. In this paper, the prevention of the attachment of test microorganism Staphylococcus epidermidis on the cerebrospinal fluid shunt surfaces by 2-hydroxyethylmethacrylate (HEMA) precursor modification in the plasma polymerization system, is reported. Different plasma polymerization conditions (RF discharge power 10-20-30 W, exposure time 5-10-15 min) were employed during the surface modification. The surface chemistry and topology of unmodified and modified shunts was characterized by x-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and atomic force microscopy (AFM). Also, static contact angle measurements were performed to state the change of surface hydrophilicity. All samples were tested in vitro with Staphylococcus epidermidis. A plasma-polymerized HEMA film (PP HEMA) was found to be an alternative simple method to decrease the microorganism attachment and create bacterial anti-fouling surfaces. The attachment of the model microorganism Staphylococcus epidermidis on the shunt surface modified by PP HEMA at 20 W and 15 min was reduced 62.3% if compared to the unmodified control surface of the shunt.

  10. Cerebrospinal fluid biomarkers of neurodegeneration in chronic neurological diseases.

    PubMed

    Tumani, Hayrettin; Teunissen, Charlotte; Süssmuth, Sigurd; Otto, Markus; Ludolph, Albert C; Brettschneider, Johannes

    2008-07-01

    Chronic neurological diseases (CND) like amyotrophic lateral sclerosis (ALS), dementia or multiple sclerosis (MS) share a chronic progressive course of disease that frequently leads to the common pathological pathway of neurodegeneration, including neuroaxonal damage, apoptosis and gliosis. There is an ongoing search for biomarkers that could support early diagnosis of CND and help to identify responders to interventions in therapeutic treatment trials. Cerebrospinal fluid (CSF) is a promising source of biomarkers in CND, since the CSF compartment is in close anatomical contact with the brain interstitial fluid, where biochemical changes related to CND are reflected. We review recent advances in CSF biomarkers research in CND and thereby focus on markers associated with neurodegeneration.

  11. Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis.

    PubMed Central

    Ernst, J D; Hartiala, K T; Goldstein, I M; Sande, M A

    1984-01-01

    Experiments were performed to identify the chemoattractant for polymorphonuclear leukocytes that appears in the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis. Meningitis was induced in anesthetized New Zealand white rabbits by injecting 10(4) cells of stationary-phase Streptococcus pneumoniae type III intracisternally. Before bacteria were injected, cerebrospinal fluid contained neither polymorphonuclear leukocytes nor chemotactic activity. Significant chemotactic activity for rabbit polymorphonuclear leukocytes was detected 12 h after inoculation with bacteria and was maximal after 18 to 20 h. Chemotactic activity appeared in cerebrospinal fluid while concentrations of pneumococci and total protein were increasing but before there was any accumulation of polymorphonuclear leukocytes. The chemotactic activity in cerebrospinal fluid was heat stable (56 degrees C for 30 min), eluted from Sephadex G-75 with a profile identical to that of the chemotactic activity in zymosan-activated rabbit serum, and was inhibited by treatment with antibodies to native human C5. In addition, preincubation of polymorphonuclear leukocytes with partially purified rabbit C5a selectively inhibited their subsequent chemotactic responses to cerebrospinal fluid. These data indicate that complement (C5)-derived chemotactic activity appears in cerebrospinal fluid during the course of experimental pneumococcal meningitis in rabbits and suggest that this activity accounts for the accumulation of polymorphonuclear leukocytes observed in this infection. PMID:6480117

  12. Cerebrospinal fluid eosinophilia associated with intraventricular shunts.

    PubMed

    Bezerra, Sofia; Frigeri, Thomas More; Severo, Carlos Marcelo; Santana, João Carlos Batista; Graeff-Teixeira, Carlos

    2011-06-01

    CSF eosinophilia (CSF-eo) is uncommon and is usually caused by helminthic infections. However, it has also been found in ∼30% of patients experiencing intraventricular shunt malfunctions. We present a case report and review the conditions associated with CSF-eo and their prophylaxis. An 8 year-old boy with tetraventricular hydrocephalus has had several shunt malfunctions over the last three years. During hospitalization in January 2009 for shunt revision, a transient 30% eosinophilia was detected in his cerebral spinal fluid (CSF) concomitant with Staphylococcus epidermidis infection and long term vancomycin administration. After several shunt replacements and antibiotic treatment, CSF-eo eventually disappeared with good overall clinical response. CSF-eo is a transient and focal event mainly associated with infection, reactions to foreign substances, particles or blood, or obstruction of tubing by normal or fibro-granulomatous tissues. Infection associated with CSF-eo is usually caused by S. epidermidis and Propioniumbacterium acnes. In addition to infection, allergy to silicone and other foreign materials may also be a cause of CSF-eo. We review the diversity of conditions and proposed mechanisms associated with CSF-eo, as well as recommendations for the care of patients with shunts. Detection of CSF-eo has been shown to be a useful indicator of shunt malfunction. As such, it provides physicians with an indicator of a hypersensitivity reaction that is underway or the need to identify bacterial infection. We also highlight the need for improved biocompatibility of shunt hardware and describe strategies to avoid conditions leading to shunt malfunction.

  13. 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.

  14. 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.

  15. 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

  16. Clinical Utility and Analytical Challenges in Measurement of Cerebrospinal Fluid Amyloid-β1–42 and τ Proteins as Alzheimer Disease Biomarkers

    PubMed Central

    Kang, Ju-Hee; Korecka, Magdalena; Toledo, Jon B.; Trojanowski, John Q.; Shaw, Leslie M.

    2014-01-01

    BACKGROUND Over the past 2 decades, clinical studies have provided evidence that cerebrospinal fluid (CSF) amyloid β1–42 (Aβ1–42), total τ(t-τ), and τ phosphorylated at Thr181 (p-τ181) are reliable biochemical markers of Alzheimer disease (AD) neuropathology. CONTENT In this review, we summarize the clinical performance and describe the major challenges for the analytical performance of the most widely used immunoassay platforms [based on ELISA or microbead-based multianalyte profiling (xMAP) technology] for the measurement of CSF AD biomarkers (Aβ1–42, t-τ, and p-τ181). With foundational immunoassay data providing the diagnostic and prognostic values of CSF AD biomarkers, the newly revised criteria for the diagnosis of AD include CSF AD biomarkers for use in research settings. In addition, it has been suggested that the selection of AD patients at the predementia stage by use of CSF AD biomarkers can improve the statistical power of clinical trial design. Owing to the lack of a replenishable and commutable human CSF-based standardized reference material (SRM) and significant differences across different immunoassay platforms, the diagnostic–prognostic cutpoints of CSF AD biomarker concentrations are not universal at this time. These challenges can be effectively met in the future, however, through collaborative ongoing standardization efforts to minimize the sources of analytical variability and to develop reference methods and SRMs. SUMMARY Measurements of CSF Aβ1–42, t-τ, and p-τ181 with analytically qualified immunoassays reliably reflect the neuropathologic hallmarks of AD in patients at the early predementia stage of the disease and even in presymptomatic patients. Thus these CSF biomarker tests are useful for early diagnosis of AD, prediction of disease progression, and efficient design of drug intervention clinical trials. PMID:23519967

  17. Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

    PubMed Central

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

    2016-01-01

    Abstract Objective To discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis. Methods 5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid. Results 5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method. Conclusion ARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

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

    PubMed

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

    2012-10-01

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

  19. 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

  20. Cerebrospinal fluid from a dog with neurologic collapse.

    PubMed

    Thompson, Craig A; Russell, Karen E; Levine, Jonathan M; Weeks, Brad R

    2003-01-01

    A 3-year-old Staffordshire Terrier was presented to the Texas Veterinary Medical Center with a short progressive history of anorexia, weight loss, and weakness that had progressed to ataxia and collapse with empirical treatment. The dog was tetraparetic and obtunded. Results of a complete neurologic evaluation were consistent with severe, multifocal to diffuse disease involving the forebrain, spinal cord, and brainstem. Cerebrospinal fluid, obtained via cerebellomedullary cisternal puncture, was highly cellular and contained large atypical round cells with small numbers of nondegenerate neutrophils and large mononuclear cells. Rare eosinophils and small lymphocytes were noted. The atypical round cells were approximately 15-25 micro m in diameter with a single nucleus set in a small amount of cytoplasm. The nuclei were typically round to slightly ovoid; however, occasional notched, lobulated, and reniform nuclei were observed. These cells were interpreted as malignant lymphocytes. Owing to a grave prognosis, the animal was euthanized and a necropsy was performed. No gross lesions were found in the central nervous system. Multiple sections of cerebellum, medulla, and spinal cord contained a diffuse neoplastic infiltrate that was predominantly meningeal with rare superficial neuropil invasion. The neoplastic cells were arranged in sheets, cords, and rosettes. Immunohistochemical staining for vimentin, pancytokeratin, CD3, CD79a, synaptophysin, S-100, and neuron-specific enolase was negative; glial fibrillary acidic protein (GFAP) staining was equivocal. Based on histologic findings, a diagnosis of medulloblastoma was made. This case documents the rare occurrence of a canine medulloblastoma and illustrates the difficulty in distinguishing between some embryonal brain tumors and lymphoma.

  1. A mathematical model of blood, cerebrospinal fluid and brain dynamics.

    PubMed

    Linninger, Andreas A; Xenos, Michalis; Sweetman, Brian; Ponkshe, Sukruti; Guo, Xiaodong; Penn, Richard

    2009-12-01

    Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid-solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.

  2. Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

    PubMed

    Parnetti, L; Gaiti, A; Polidori, M C; Brunetti, M; Palumbo, B; Chionne, F; Cadini, D; Cecchetti, R; Senin, U

    1995-10-27

    Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

  3. 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.

  4. 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

  5. Extremely rare complications in cerebrospinal fluid shunt operations.

    PubMed

    Surchev, J; Georgiev, K; Enchev, Y; Avramov, R

    2002-06-01

    The cerebrospinal fluid shunt operation, from its first realization in 1908 by Kausch till our days, is still of a significant importance for the long-term treatment of the internal hydrocephalus. Well known are many complications connected with the use of the valve systems (malfunction, infectious, overdrainage, secondary craniosynostosis and etc.). For a period of 17 years (1984-2000) at the Clinic of Pediatric Neurosurgery, Department of Neurosurgery, Sofia Medical University, 414 cerebrospinal fluid shunt operations were performed on children. 216 were drained to the right atrium of the heart, 198 to the peritoneal cavity. They were followed up by catamnesis until the year 2001. The authors describe 2 extremely rare cases with post-shunt complication as a result of a malfunction of the valve system, owing to a migration of the distal catheter: 1) in the anus; 2) in the urethra. In the first case the distal catheter perforated the colon transversum and by the way of the intestines went out through the anus. In the second case the distal catheter protruded out of the body through the bladder and the urethra. Their clinical appearance, the diagnostic examinations and the operative treatment are shown.

  6. Cytologic diagnosis of spinal cord ependymoma in cerebrospinal fluid.

    PubMed

    Kalogeraki, A; Tamiolakis, D; Sinatkas, V; Xekalou, A; Papadakis, M; Stathopoulos, E N

    2012-12-01

    Ependymoma cells are known to rarely exfoliate into cerebrospinal fluid (CSF). However, the frequency of CSF involvement in patients with ependymoma is unclear, and to the author's knowledge the cytomorphologic features of tumour cells have not been well described to date. In this study, the CSF findings in a patient with ependymoma and the cytopathological features of this tumor are reported. The patient presented at the University Hospital of Heraklion, Crete, suffering from a chest to back pain. Computed tomography, scanning and magnetic resonance imaging (MRI) were performed and a mass of 3x2 cm in the thoracic aspect of the spinal cord was found. A sample of cerebrospinal fluid (CSF) was sent for cytologic examination and a diagnosis of ependymoma was made. A biopsy was performed and histology confirmed the cytologic diagnosis of ependymoma grade II (WHO). Exfoliated cells from ependymomas of spinal cord are rarely recognizable in CSF samples. Except in patients with myxopapillary tumours and anaplastic tumours, cytomorphologic features of ependymoma have been described only in case reports of intraoperative imprinting or fine needle aspiration biopsies (FNABs) and not in CSF cytology.

  7. The function and structure of the cerebrospinal fluid outflow system

    PubMed Central

    2010-01-01

    This review traces the development of our understanding of the anatomy and physiological properties of the two systems responsible for the drainage of cerebrospinal fluid (CSF) into the systemic circulation. The roles of the cranial and spinal arachnoid villi (AV) and the lymphatic outflow systems are evaluated as to the dominance of one over the other in various species and degree of animal maturation. The functional capabilities of the total CSF drainage system are presented, with evidence that the duality of the system is supported by the changes in fluid outflow dynamics in human and sub-human primates in hydrocephalus. The review also reconciles the relative importance and alterations of each of the outflow systems in a variety of clinical pathological conditions. PMID:20565964

  8. 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.

  9. 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Staroń, Waldemar; Herbowski, Leszek; Gurgul, Henryk

    2007-04-01

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

  12. Endoscopic Transmaxillary Transposition of Temporalis Flap for Recurrent Cerebrospinal Fluid Leak Closure.

    PubMed

    Thomas, Regi; Girishan, Shabari; Chacko, Ari George

    2016-12-01

    Objective To describe the technique of endoscopic transmaxillary temporalis muscle flap transposition for the repair of a persistent postoperative sphenoidal cerebrospinal fluid leak. Design The repair of a recurrent cerebrospinal fluid leak for a patient who had undergone endoscopic transsphenoidal excision of an invasive silent corticotroph Hardy C and Knosp Grade IV pituitary adenoma was undertaken. The patient had completed postoperative radiotherapy for the residual tumor and presented with cerebrospinal fluid leak, 1 year later. The initial two attempts to repair the cerebrospinal fluid leak with free grafts failed. Therefore, an endoscopic transmaxillary transposition of the temporalis muscle flap was attempted to stop the cerebrospinal fluid leak. Results The endoscopic transmaxillary transposition of the vascularized temporalis muscle flap onto the cerebrospinal fluid leak repair site resulted in successful closure of the cerebrospinal fluid leak. Conclusion Endoscopic transmaxillary transposition of the temporalis flap resulted in closure of recurrent cerebrospinal fluid leak in a patient with recurrent pituitary adenoma, who had undergone previous surgery and radiotherapy. This technique has advantages over the endoscopic transpterygoid transposition of the same flap and could be used as a complementary technique in selected patients.

  13. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury.

    PubMed

    Zhang, Yan-Bo; Guo, Zheng-Dong; Li, Mei-Yi; Li, Si-Jie; Niu, Jing-Zhong; Yang, Ming-Feng; Ji, Xun-Ming; Lv, Guo-Wei

    2015-09-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.

  14. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury

    PubMed Central

    Zhang, Yan-bo; Guo, Zheng-dong; Li, Mei-yi; Li, Si-jie; Niu, Jing-zhong; Yang, Ming-feng; Ji, Xun-ming; Lv, Guo-wei

    2015-01-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats. PMID:26604909

  15. Total-tau and phospho-tau(181Thr) in cerebrospinal fluid of neurologically intact population increase with age.

    PubMed

    Jaworski, J; Psujek, M; Bartosik-Psujek, H

    2009-01-01

    Tau protein is a microtubule-associated molecule playing a crucial role in maintenance of neuronal integrity and in many neurodegenerative processes; its pathology has become a hallmark feature at the tissue level. The aim of the study was to estimate total tau and phospho-tau (Thr181) concentrations in cerebrospinal fluid of healthy population. Cerebrospinal fluid samples were taken from 129 subjects (age 18-77 years) without known neurologic or psychiatric condition. Both total-tau and phospho-tau levels showed significant correlation with age, which was more pronounced in older population.

  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. 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

    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

    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.

  18. 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.

  19. Properties of extracellular DNA from the cerebrospinal fluid and blood plasma during Parkinson's disease.

    PubMed

    Glebova, K V; Konorova, I L; Poleshchuk, V V; Baidakova, G V; Veiko, N N

    2014-04-01

    The cerebrospinal fluid of patients with Parkinson's disease was shown to contain extracellular DNA. Extracellular DNA concentration in the cerebrospinal fluid was 3.3-fold lower than in blood plasma from these patients. HPLC-mass spectrometry analysis showed that the pool of extracellular DNA from the liquor is characterized by a lower content of deoxythymidine, but greater amounts of deoxycytidine and deoxyguanosine than the pool of extracellular DNA from the plasma. The level of deoxyguanosine was 2 times lower than that of deoxycytidine (as differentiated from plasma extracellular DNA with similar content of these substances). Our findings indicate that extracellular DNA from the cerebrospinal fluid contains considerable amounts of modified deoxyguanosine. These data attest to significant differences in the quantitative and qualitative characteristics of extracellular DNA from the blood and cerebrospinal fluid of patients. Specific features of extracellular DNA from the cerebrospinal fluid of patients suggest its involvement in the pathogenesis of Parkinson's disease.

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

    PubMed Central

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

    2014-01-01

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

  1. [Two cases of herpes encephalitis with normal cerebrospinal fluid findings].

    PubMed

    Avkan Oğuz, Vildan; Yapar, Nur; Sezak, Nurbanu; Alp Cavuş, Sema; Kuruüzüm, Ziya; Sayiner, Arzu; Ada, Emel; Cakir, Nedim; Yüce, Ayşe

    2006-01-01

    In this report, characteristics of two cases of Herpes simplex virus (HSV) encephalitis with normal cerebrospinal fluid (CSF) findings at the time of admission have been discussed and the current literature has been reviewed. The diagnosis of the cases (one was 23 years old male, and the other was 75 years old female patient) was made on the magnetic resonance imaging (MRI) findings concordant with HSV encephalitis, together with HSV-1 DNA positivity by polymerase chain reaction (PCR). Both of the patients were treated with acyclovir (3 x 750 mg/day) lasting for 15 days and 21 days, respectively. The first male patient recovered with mild neurological defects, whereas the second female patient died because of nosocomial pneumonia and septicemia. In conclusion, even the CSF findings are normal, in cases considered to be HSV encephalitis, MRI should be the first radiological diagnostic step and the diagnosis should be confirmed by the detection of HSV DNA in CSF by PCR.

  2. Acetylcholinesterase activity in the cerebrospinal fluid of dogs with seizures.

    PubMed

    Chai, Orit; Sommer, Adi; Zimmerman, Gabriel; Soreq, Hermona; Friedman, Alon; Bdolah-Abram, Tali; Aroch, Itamar; Shamir, Merav H

    2013-10-01

    Recent studies in animal models have focused on the role of cholinergic elements, mainly acetylcholinesterase (AChE) and the 'readthrough' acetylcholinesterase isoform (AChE-R), in seizures. A prospective double-masked study was conducted to assess the activity of AChE and AChE-R in cerebrospinal fluid (CSF) of 26 dogs post-seizure, 28 dogs with intervertebral disc disease (IVDD) and 16 healthy dogs. AChE was also measured in the serum in the post-seizure and IVDD groups. The results showed no significant differences in CSF AChE among the three groups. AChE-R was not detected in any dog and AChE in the serum was similar between groups. This preliminary study provides new information on AChE and AChE-R in the CSF and sera of dogs following naturally-occurring seizures.

  3. 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

  4. 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.

  5. A Subglandular Breast Cerebrospinal Fluid Pseudocyst Following Postsurgical Shunt Migration

    PubMed Central

    Mlynek, Karolina; Frautschi, Russell; Halasa, Brianna; Kwiecien, Grzegorz

    2015-01-01

    Summary: Cerebrospinal fluid (CSF) drainage catheters have been associated with numerous complications in various anatomic locations, because of migration, infection, and obstruction. However, breast-related CSF shunt complications tend to occur infrequently or have seldom been reported in the empirical literature. Therefore, a case is presented detailing a breast pseudocyst caused by migration and subsequent coiling of a ventriculoperitoneal shunt in the right breast pocket. To the best of the authors’ knowledge, this is the first case that has been reported in the peer-reviewed literature of a pseudocyst resulting from a CSF drainage catheter coiling around the breast implant post pancreaticoduodenectomy. Moreover, this case highlights the importance of cross-disciplinary procedural awareness, particularly in regards to breast, ventriculoperitoneal shunt, and pancreatic procedures. PMID:26894004

  6. A Subglandular Breast Cerebrospinal Fluid Pseudocyst Following Postsurgical Shunt Migration.

    PubMed

    Mlynek, Karolina; Frautschi, Russell; Halasa, Brianna; Kwiecien, Grzegorz; Papay, Francis

    2015-12-01

    Cerebrospinal fluid (CSF) drainage catheters have been associated with numerous complications in various anatomic locations, because of migration, infection, and obstruction. However, breast-related CSF shunt complications tend to occur infrequently or have seldom been reported in the empirical literature. Therefore, a case is presented detailing a breast pseudocyst caused by migration and subsequent coiling of a ventriculoperitoneal shunt in the right breast pocket. To the best of the authors' knowledge, this is the first case that has been reported in the peer-reviewed literature of a pseudocyst resulting from a CSF drainage catheter coiling around the breast implant post pancreaticoduodenectomy. Moreover, this case highlights the importance of cross-disciplinary procedural awareness, particularly in regards to breast, ventriculoperitoneal shunt, and pancreatic procedures.

  7. Agitation in Dementia: Relation to Core Cerebrospinal Fluid Biomarker Levels

    PubMed Central

    Bloniecki, Victor; Aarsland, Dag; Cummings, Jeffrey; Blennow, Kaj; Freund-Levi, Yvonne

    2014-01-01

    Background The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and Aβ1-42. Methods One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points). Results Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95). Conclusions Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD. PMID:25298777

  8. [Alpha-2 macroglobulin from cerebrospinal fluid in neurosurgical diseases].

    PubMed

    Vasil'eva, T G; Dobrogorskaia, L N; Kraeva, L N; Goncharova, V P

    1989-01-01

    Content of alpha 2-macroglobulin (alpha 2-MG) was estimated in cerebrospinal fluid (CSF) of patients with neurosurgical impairments. Minimal content of the globulin was found in patients with brain concussion (0.011 +/- 0.001 g/L, control group), maximal concentration--in severe craniocerebral trauma with brain contraction (0.056 +/- 0.007 g/L) and moderately increased content of alpha 2-MG was detected in intracranial tumors and drug-resistant epilepsy, 0.028 +/- 0.004 g/L and 0.025 +/- 0.004 g/L, respectively. Alteration in content of alpha 2-MG during postoperational period corresponded to clinical state of patients. Estimation of alpha 2-MG in CSF might be used as a criterion of brain impairment severity as well as for monitoring the treatment course.

  9. Cerebrospinal fluid centesis at the cerebellomedullary cistern of kittens.

    PubMed

    Hudson, Lola C; Vahlenkamp, Thomas W; Howard; Colby, Brenda; Tompkins; Meeker, Rick B

    2002-09-01

    We needed an effective technique for obtaining cerebrospinal fluid (CSF) from young (2- to 18-week-old) kittens. Standard veterinary technique was not suitable, so we adapted a previously published technique for rats. We first established an effective isoflurane-only anesthetic protocol for young kittens. After inhalant anesthesia, the kittens were positioned on a supporting platform to gain flexion of the head and neck. A micromanipulator was used to hold and slowly advance the collection needle. At the time this report was written, we had collected a total of 33 samples from eight kittens without causing apparent neurologic deficits. Correct positioning of the animal and collection needle was critical for success. This procedure enabled the collection of approximately 0.5 ml CSF from kittens younger than 12 weeks and larger volumes from older kittens.

  10. Cerebrospinal-fluid concentrations of nitrazepam in man.

    PubMed

    Kangas, L; Kanto, J; Siirtola, T; Pekkarinen, A

    1977-07-01

    The concentrations of nitrazepam in the plasma and cerebrospinal-fluid (CSF) of 38 neurological patients were determined by gas chromatography 2-36 hours after a single 5 mg oral dose. The percentage ratio between the mean CSF and the plasma concentrations increased from 8.0% at 2 hours to 15.6% at 36 hours. This percentage rise was significant (P less than 0.001). The maximum concentration of nitrazepam in the plasma was 36.7 +/- 5.7 ng/ml (at 2 hours) and CSF 3.0 +/- 0.3 ng/ml (at 4 hours). During the beta-phase the half-life of nitrazepam in plasma was about 27 hours and in the CSF markedly longer about 68 hours, indicating a very slow elimination of nitrazepam from the CSF.

  11. Cerebrospinal fluid flow dynamics in the central nervous system.

    PubMed

    Sweetman, Brian; Linninger, Andreas A

    2011-01-01

    Cine-phase-contrast-MRI was used to measure the three-dimensional cerebrospinal fluid (CSF) flow field inside the central nervous system (CNS) of a healthy subject. Image reconstruction and grid generation tools were then used to develop a three-dimensional fluid-structure interaction model of the CSF flow inside the CNS. The CSF spaces were discretized using the finite-element method and the constitutive equations for fluid and solid motion solved in ADINA-FSI 8.6. Model predictions of CSF velocity magnitude and stroke volume were found to be in excellent agreement with the experimental data. CSF pressure gradients and amplitudes were computed in all regions of the CNS. The computed pressure gradients and amplitudes closely match values obtained clinically. The highest pressure amplitude of 77 Pa was predicted to occur in the lateral ventricles. The pressure gradient between the lateral ventricles and the lumbar region of the spinal canal did not exceed 132 Pa (~1 mmHg) at any time during the cardiac cycle. The pressure wave speed in the spinal canal was predicted and found to agree closely with values previously reported in the literature. Finally, the forward and backward motion of the CSF in the ventricles was visualized, revealing the complex mixing patterns in the CSF spaces. The mathematical model presented in this article is a prerequisite for developing a mechanistic understanding of the relationships among vasculature pulsations, CSF flow, and CSF pressure waves in the CNS.

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

    DOE PAGES

    Hyung, Seok Won; Piehowski, Paul D.; Moore, Ronald J.; ...

    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

  13. 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.

  14. Idiopathic cerebrospinal fluid overproduction: case-based review of the pathophysiological mechanism implied in the cerebrospinal fluid production.

    PubMed

    Trevisi, Gianluca; Frassanito, Paolo; Di Rocco, Concezio

    2014-08-28

    Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications.

  15. Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: a pathogenetically based approach.

    PubMed

    van Dijk, Karin D; Teunissen, Charlotte E; Drukarch, Benjamin; Jimenez, Connie R; Groenewegen, Henk J; Berendse, Henk W; van de Berg, Wilma D J

    2010-09-01

    The inaccuracy of the early diagnosis of Parkinson's disease (PD) has been a major incentive for studies aimed at the identification of biomarkers. Brain-derived cerebrospinal fluid (CSF) proteins are potential biomarkers considering the major role that proteins play in PD pathogenesis. In this review, we discuss the current hypotheses about the pathogenesis of PD and identify the most promising candidate biomarkers among the CSF proteins studied so far. The list of potential markers includes proteins involved in various pathogenetic processes, such as oxidative stress and protein aggregation. This list will undoubtedly grow in the near future by application of CSF proteomics and subsequent validation of identified proteins. Probably a single biomarker will not suffice to reach high sensitivity and specificity, because PD is pathogenetically heterogeneous and shares etiological factors with other neurodegenerative diseases. Furthermore, identified candidate biomarkers will have to be thoroughly validated before they can be implemented as diagnostic aids.

  16. Highly potent soluble amyloid-β seeds in human Alzheimer brain but not cerebrospinal fluid

    PubMed Central

    Kaeser, Stephan A.; Maia, Luis F.; Portelius, Erik; Pinotsi, Dorothea; Kaminski, Clemens F.; Winkler, David T.; Maetzler, Walter; Keyvani, Kathy; Spitzer, Philipp; Wiltfang, Jens; Kaminski Schierle, Gabriele S.; Zetterberg, Henrik; Staufenbiel, Matthias; Jucker, Mathias

    2017-01-01

    The soluble fraction of brain samples from patients with Alzheimer’s disease contains highly biologically active amyloid-β seeds. In this study, we sought to assess the potency of soluble amyloid-β seeds derived from the brain and cerebrospinal fluid. Soluble Alzheimer’s disease brain extracts were serially diluted and then injected into the hippocampus of young, APP transgenic mice. Eight months later, seeded amyloid-β deposition was evident even when the hippocampus received subattomole amounts of brain-derived amyloid-β. In contrast, cerebrospinal fluid from patients with Alzheimer’s disease, which contained more than 10-fold higher levels of amyloid-β peptide than the most concentrated soluble brain extracts, did not induce detectable seeding activity in vivo. Similarly, cerebrospinal fluid from aged APP-transgenic donor mice failed to induce cerebral amyloid-β deposition. In comparison to the soluble brain fraction, cerebrospinal fluid largely lacked N-terminally truncated amyloid-β species and exhibited smaller amyloid-β-positive particles, features that may contribute to the lack of in vivo seeding by cerebrospinal fluid. Interestingly, the same cerebrospinal fluid showed at least some seeding activity in an in vitro assay. The present results indicate that the biological seeding activity of soluble amyloid-β species is orders of magnitude greater in brain extracts than in the cerebrospinal fluid. PMID:25212850

  17. 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.

  18. Rapid distribution of intraventricularly administered sucrose into cerebrospinal fluid cisterns via subarachnoid velae in rat.

    PubMed

    Ghersi-Egea, J F; Finnegan, W; Chen, J L; Fenstermacher, J D

    1996-12-01

    perivascular spaces and/or walls of pial arteries and arterioles for more than 3 h. Certain transport proteins, protease inhibitors, growth factors and other neurobiologically active materials are present in cerebrospinal fluid, and their distribution to the brain and its blood vessels may be important. The present work shows, in the rat, that the flow of cerebrospinal fluid and the disposition of its constituents is fairly complex and differs among regions. Flow was rapid throughout the ventricular system and into various subarachnoid velae and cisterns, but was surprisingly slow and slight over the cerebral and cerebellar cortices. The cerebrospinal fluid-to-tissue flux of material was relatively free at many interfaces, but was greatly restricted at others, the latter indicating that the old concept of a "cerebrospinal fluid-brain barrier" may hold at such places. Finally, radiolabeled sucrose was retained longer within the walls and perivascular spaces of pial arteries and arterioles than in other subarachnoid tissues; one function of the cerebrospinal fluid system or "third circulation" may thus be delivering factors and agents to these pial blood vessels.

  19. Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer's Disease in Clinical Practice: An Illustration with 3 Case Reports

    PubMed Central

    Slats, Diane; Spies, Petra E.; Sjögren, Magnus J.C.; Verhey, Frans R.J.; Verbeek, Marcel M.; Olde Rikkert, Marcel G.M.

    2010-01-01

    Analysis of the brain specific biomarkers amyloid β42 (Aβ42) and total tau (t-tau) protein in cerebrospinal fluid (CSF) has a sensitivity and specificity of more than 85% for differentiating Alzheimer's Disease (AD) from non-demented controls. International guidelines are contradictory in their advice on the use of CSF biomarkers in AD diagnostics, resulting in a lack of consistency in clinical practice. We present three case reports that illustrate clinical practice according to the Dutch and European guidelines and portray the value of CSF biomarker analysis as an add-on diagnostic to the standard diagnostic workup for AD. PMID:20689628

  20. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    PubMed

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Palmqvist, Sebastian; Mattsson, Niklas; Hansson, Oskar

    2016-04-01

    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 (18)F-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 adjustments of different factors and when using different cut-offs for amyloid-β abnormality

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

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2015-01-01

    Background: Meningitis remains a serious clinical problem in developing as well as developed countries. Delay in diagnosis and treatment results in significant morbidity and mortality. The role and levels of intrathecal endogenous cortisol is not known. Objective: To study the cerebrospinal fluid (CSF) cortisol levels and to evaluate its role as a diagnostic and therapeutic marker in acute bacterial meningitis. Materials and Methods: Thirty patients with acute bacterial meningitis with no prior treatment were evaluated. Cortisol levels were compared with 20 patients with aseptic (viral) meningitis and 25 control subjects. Results: Mean CSF cortisol level was 13.85, 3.47, and 1.05 in bacterial meningitis, aseptic meningitis, and controls, respectively. Mean CSF cortisol level in bacterial meningitis was significantly higher as compared to controls (P < 0.001). There was significant difference in CSFcortisol levels in bacterial and aseptic meningitis (P < 0.001). Conclusions: Cortisol levels in CSF are highly elevated in patients with acute bacterial meningitis. This suggests that intrathecalcortisol may serve as a valuable, rapid, relatively inexpensive diagnostic marker in discriminatingbetween bacterial and aseptic meningitis. This helps in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. PMID:26019421

  5. Subtotal petrosectomy and cerebrospinal fluid leakage in unilateral anacusis.

    PubMed

    Magliulo, Giuseppe; Iannella, Giannicola; Ciniglio Appiani, Mario; Re, Massimo

    2014-12-01

    Objective This study presents a group of patients experiencing recurrent cerebrospinal fluid (CSF) leakage associated with ipsilateral anacusis who underwent subtotal petrosectomies with the goal of stopping the CSF leak and preventing meningitis. Materials and Methods Eight patients with CSF leakage were enrolled: three patients with giant vestibular schwannomas had CSF leakage after gamma knife failure and subsequent removal via a retrosigmoid approach; two patients had malformations at the level of the inner ear with consequent translabyrinthine fistulas; two had posttraumatic CSF leakages; and one had a CSF leakage coexisting with an encephalocele. Two patients developed meningitis that resolved with antibiotic therapy. Each patient had preoperative anacusis and vestibular nerve areflexia on the affected side. Results The patients with congenital or posttraumatic CSF leaks had undergone at least one unsuccessful endaural approach to treat the fistula. All eight patients were treated successfully with a subtotal petrosectomy. The symptoms disappeared within 2 months postoperatively. No meningitis, signs of fistula, or other symptoms occurred during the follow-up. Conclusion A subtotal petrosectomy should be the first choice of treatment in patients with recurrent CSF leakage whenever there is associated unilateral anacusis.

  6. Subtotal Petrosectomy and Cerebrospinal Fluid Leakage in Unilateral Anacusis

    PubMed Central

    Magliulo, Giuseppe; Iannella, Giannicola; Appiani, Mario Ciniglio; Re, Massimo

    2014-01-01

    Objective This study presents a group of patients experiencing recurrent cerebrospinal fluid (CSF) leakage associated with ipsilateral anacusis who underwent subtotal petrosectomies with the goal of stopping the CSF leak and preventing meningitis. Materials and Methods Eight patients with CSF leakage were enrolled: three patients with giant vestibular schwannomas had CSF leakage after gamma knife failure and subsequent removal via a retrosigmoid approach; two patients had malformations at the level of the inner ear with consequent translabyrinthine fistulas; two had posttraumatic CSF leakages; and one had a CSF leakage coexisting with an encephalocele. Two patients developed meningitis that resolved with antibiotic therapy. Each patient had preoperative anacusis and vestibular nerve areflexia on the affected side. Results The patients with congenital or posttraumatic CSF leaks had undergone at least one unsuccessful endaural approach to treat the fistula. All eight patients were treated successfully with a subtotal petrosectomy. The symptoms disappeared within 2 months postoperatively. No meningitis, signs of fistula, or other symptoms occurred during the follow-up. Conclusion A subtotal petrosectomy should be the first choice of treatment in patients with recurrent CSF leakage whenever there is associated unilateral anacusis. PMID:25452896

  7. Cerebrospinal fluid neopterin and cryopyrin-associated periodic syndrome.

    PubMed

    Serrano, Mercedes; Ormazábal, Aida; Antón, Jordi; Aróstegui, Juan I; García-Cazorla, Angels

    2009-12-01

    Cryopyrin-associated periodic syndrome is a category of autoinflammatory disorders caused by mutations of the NLRP3 gene, with chronic infantile neurologic cutaneous and articular syndrome being the severest clinical phenotype. Various pterins have been reported as mediating immunologic functions in the central nervous system, but to date studies of pterin cerebrospinal fluid (CSF) values and cryopyrin-associated periodic syndrome have been lacking. A 2-year-old child was affected with a severe atypical form of cryopyrin-associated periodic syndrome, suspected based on the analysis of neopterin in CSF. He initially presented isolated neurologic manifestations mimicking a neuroregressive disorder. Blood and CSF analyses did not present any routine inflammatory markers, but CSF neopterin was elevated. Later, the patient developed arthritis and recurrent episodes of fever, and the cryopyrin-associated periodic syndrome diagnosis was confirmed by genetic studies. Neopterin was the most altered indicator over the time. Child neurologists should be on the alert when unexplained neurologic signs appear, giving consideration to the possibility of inflammatory or immune-mediated diseases. The present case demonstrates the clinical utility of measurement of CSF neopterin levels in screening for these immune-mediated diseases, especially when neurologic symptoms are associated with normal results on routine CSF tests.

  8. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.

    PubMed

    Blennow, Kaj; Hampel, Harald; Weiner, Michael; Zetterberg, Henrik

    2010-03-01

    Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid-beta immunotherapy and secretase inhibition, are now being tested in clinical trials. Disease-modifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. In this Review, we present the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-beta. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. We also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, we outline the roles of CSF biomarkers in drug discovery and clinical trials, and provide perspectives on AD biomarker discovery and the validation of such markers for use in the clinic.

  9. Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects.

    PubMed

    Albeck, M J; Børgesen, S E; Gjerris, F; Schmidt, J F; Sørensen, P S

    1991-04-01

    Conductance of cerebrospinal fluid (CSF) outflow (Cout) is an important parameter to be considered in patients with CSF circulation abnormalities. In patients with normal-pressure hydrocephalus it is the single most important parameter in determining if the patient needs CSF shunting. The lower normal limit for Cout has been estimated from the effect of shunting in patients with normal-pressure hydrocephalus, from patients retrospectively reevaluated after recovering from illness, and from patients with known abnormalities in the brain or the CSF system. The true value of Cout in normal individuals, however, has hitherto not been reported. In the present study, Cout has been measured by a lumbar infusion test in eight young volunteers with no suspicion of disease. The mean intracranial pressure (ICP) was 11 mm Hg and a linear relationship was found between CSF absorption and ICP. The mean Cout was 0.11 ml/min/mm Hg and the lower 95% confidence level was 0.10 ml/min/mm Hg. These values are in accordance with those obtained from previous studies.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Florbetapir positron emission tomography and cerebrospinal fluid biomarkers

    PubMed Central

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

    2015-01-01

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

  16. Free and Total Vitamin B12 in Cerebrospinal Fluid

    PubMed Central

    Kidd, Honor M.; Gould, C. E. G.; Thomas, J. W.

    1963-01-01

    Free and total vitamin B12 levels in serum and cerebrospinal fluid (CSF) were bioassayed, since there were no available data on the relationship between free and total vitamin B12 in CSF or between free vitamin in serum and CSF vitamin B12. The subjects were 43 neurological patients. Serum levels were normal in 40 of 43 patients. Values for free and total vitamin B12 in CSF were the same in 42 of 43 patients. Mean CSF vitamin B12 was 21 μμg./ml. In 17 cases CSF vitamin B12 equalled free vitamin B12 level in serum, in 16 cases CSF vitamin B12 was lower than the free level in serum, and in 10 cases CSF vitamin B12 was higher than the free vitamin level in serum. There was no apparent diagnostic correlation. The findings suggest that vitamin B12 is not bound in CSF and that there is some selective control of passage of vitamin B12 across the blood-CSF barrier. PMID:14032478

  17. Cerebrospinal fluid ascorbic acid levels in neurological disorders.

    PubMed

    Brau, R H; García-Castiñeiras, S; Rifkinson, N

    1984-02-01

    The ascorbic acid/dehydroascorbic acid system was analyzed in the cerebrospinal fluid (CSF) of 41 patients with different neurological disorders. The chi-square test of covariance analysis revealed in this sample significant differences in the CSF levels of total ascorbic acid when patients were classified by diagnostic categories. The population analyzed contained a group of 18 patients (back pain/sciatica group) in whom no overt neurological abnormalities were disclosed upon evaluation. Taking the CSF levels of total ascorbic acid and dehydroascorbic acid in these patients as the reference (3.57 +/- 0.87 (SD)/100 ml and 0.53 +/- 0.19 mg/100 ml, respectively), it was found that head-traumatized patients showed a significant reduction in the concentration of total ascorbic acid in the CSF. CSF ascorbic acid levels were also significantly lower in patients with increased intracranial pressure (noninfected hydrocephalus group) and in patients with cerebral tumors. Although the CSF concentration of dehydroascorbic acid did not correspondingly increase over the reference values in these three groups of patients, the tendency existed for dehydroascorbic acid to represent in them a higher percentage of total ascorbic acid. After examining different alternatives, it is concluded that the hypothesis of free radical damage to the central nervous system after certain types of injury (trauma, ischemia, and tumors) may provide a satisfactory explanation of our findings. A rationale for the use of vitamin C in the management of some neurological patients is also derived from this work.

  18. 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

  19. Balzac's serous apoplexies. The hesitant acceptance of the discovery of the cerebrospinal fluid by Magendie.

    PubMed

    van den Doel, E M

    1987-12-01

    The diagnosis of a "serous apoplexy," customary in the first half of the 19th century, was based on the lack of knowledge regarding the normal presence of the cerebrospinal fluid. Balzac's descriptions of three cases of serous apoplexy draw our attention to the fact that the discovery of the cerebrospinal fluid by François Magendie was not assimilated into clinical medicine until the second half of the 19th century.

  20. 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.

  1. Cerebrospinal Fluid Cytological Diagnosis in Multiple Myeloma With Leptomeningeal Involvement: A Report of Two Cases.

    PubMed

    Ren, Haitao; Zou, Yueli; Zhao, Yanhuan; Li, Jian; Han, Xiao; He, Junying; Guan, Hongzhi

    2017-01-01

    Multiple myeloma (MM) with central nervous system (CNS) infiltration is uncommon and the diagnosis is more complicated than that of MM. Here we report two cases of CNS MM that was diagnosed by cerebrospinal fluid cytology examination. Cerebrospinal fluid cytology examination can help to detect malignant cells and immunocytochemistry stain is of great value in identifying an unknown tumor. Diagn. Cytopathol. 2017;45:66-68. © 2016 Wiley Periodicals, Inc.

  2. Tau, phospho-tau, and S-100B in the cerebrospinal fluid of children with multiple sclerosis.

    PubMed

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

    2005-10-01

    Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins using specific enzyme-linked immunoabsorbent assays. In general, tau, phospho-tau, and S-100B protein levels did not differ significantly between groups. However, in a subgroup of nine children with multiple sclerosis, all of whom had prominent clinical symptoms at the time of lumbar puncture and radiologic disease activity, tau protein levels were significantly elevated when compared with other controls. These data indicate that axonal injury is not restricted to adult multiple sclerosis but can already occur in children with multiple sclerosis.

  3. Cerebrospinal fluid lens-free microscopy: a new tool for the laboratory diagnosis of meningitis

    PubMed Central

    Delacroix, Robin; Morel, Sophie Nhu An; Hervé, Lionel; Bordy, Thomas; Dinten, Jean-Marc; Drancourt, Michel; Allier, Cédric

    2017-01-01

    Cerebrospinal fluid cytology is performed by operator-dependant light microscopy as part of the routine laboratory work-flow diagnosis of meningitis. We evaluated operator-independent lens-free microscopy numeration of erythrocytes and leukocytes for the cytological diagnosis of meningitis. In a first step, prospective optical microscopy counts of leukocytes done by five different operators yielded an overall 16.7% misclassification of 72 cerebrospinal fluid specimens in meningitis/non-meningitis categories using a 10 leukocyte/μL cut-off. In a second step, the lens-free microscopy algorithm adapted for counting cerebrospinal fluid cells and discriminating leukocytes from erythrocytes was modified step-by-step in the prospective analysis of 215 cerebrospinal fluid specimens. The definite algorithm yielded a 100% sensitivity and a 86% specificity compared to confirmed diagnostics. In a third step, a blind lens-free microscopic analysis of 116 cerebrospinal fluid specimens, including six cases of microbiology-confirmed infectious meningitis, yielded a 100% sensitivity and a 79% specificity. Adapted lens-free microscopy is thus emerging as an operator-independent technique for the rapid numeration of leukocytes and erythrocytes in cerebrospinal fluid. In particular, this technique is well suited to the rapid diagnosis of meningitis at point-of-care laboratories. PMID:28045084

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

    PubMed

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

    2014-12-01

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

  5. Bicompartmental analysis of cerebrospinal fluid circulation. Theory and clinical applications.

    PubMed

    Cabanes, J; Marti, J; Orozco, M; Beltran, A

    1983-08-01

    A new model for cerebrospinal fluid (CSF) circulation is proposed. Specific activity/time curves for CSF kinetics determined after intraventricular injection of a radiotracer were produced by fitting a biexponential function to data points and developing a two-compartmental model. Calculation of kinetic parameters of the model provides quantitative data about CSF dynamics. The study of each compartment separately and of the intercompartmental relationship is possible with this model. Sequential scan images and graphic plots of the variations of radioactivity in both compartments, derived from this model, add supplementary information in the evaluation of patients. Ventriculography was performed in 80 patients, who fell into four groups: those with normal CSF circulation, hydrocephalus, infantile hydrocephalus, and functioning ventricular shunts. Normal and hydrocephalic patients showed significant differences between the two groups in the means of some numerical parameters calculated from the new model. An increase of intraventricular radioactivity at 24 hours (p less than 10(-4)) and of the volume of Compartment 1 (p less than 0.01) with decreased volume of Compartment 2 (p less than 10(-4)) and total flow outside the system (p less than 10(-3)) were found in patients with hydrocephalus. The limiting values for normal patients were also estimated. Communicating and obstructive hydrocephalus could be differentiated by this method; however, no differences in mean values were found relating to the etiology or clinical course of the hydrocephalus. Normal-pressure hydrocephalus and cerebral atrophy produced significantly different mean values for the volume of Compartment 2 (p less than 0.01), flow out of the system (p less than 0.01), and intercompartmental flow (p less than 0.01).

  6. 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

  7. Management of Cerebrospinal Fluid Leak following Posterior Cranial Fossa Surgery

    PubMed Central

    Altaf, Imran; Vohra, Anjum Habib; Shams, Shahzad

    2016-01-01

    Objective: Cerebrospinal fluid leakage remains a significant cause of morbidity following posterior fossa surgery, and its treatment remains a difficult problem. The aim of the study was to propose a treatment algorithm for its management. Methods: A retrospective, single-center study was conducted on 147 patients who underwent elective posterior fossa surgery for a variety of diseases. Patients with post operative CSF leakage had either been treated initially with conservative measures including re-suturing of the wound, with CSF lumbar drainage to be employed in case the CSF leakage didn’t stop, or the initial intervention was the institution of CSF lumbar drainage simultaneously with conservative measures. VP (ventriculo-peritoneal) shunt was done in patients with gross hydrocephalus on postoperative CT brain. Results: There were 25 (17%) cases of CSF leakage, including 24 incisional CSF leaks and one case of CSF otorrhea. In eight patients with incisional CSF leakage treated initially with conservative measures including re-suturing of the wound, CSF leakage stopped in only two cases. CSF lumbar drainage instituted later on in six cases with persistent leakage stopped the CSF leakage. In fourteen patients managed initially with re-suturing of the wound and concomitant CSF lumbar drainage, CSF leakage settled in all the cases. Two patients with gross hydrocephalus on post operative CT were managed successfully with VP shunt. Re-suturing of the wound with concomitant CSF lumbar drainage was found to be significantly associated (p=0.003) with the stoppage of CSF leakage, and the settlement of meningitis (p= 0.014). Conclusion: Incisional CSF leaks after posterior fossa surgery should be managed with re-suturing of the wound and concomitant CSF lumbar drainage, instead of an initial trial of conservative therapy alone. PMID:28083041

  8. Alterations in Cerebrospinal Fluid in Patients with Bipolar Syndromes

    PubMed Central

    Endres, Dominique; Dersch, Rick; Hottenrott, Tilman; Perlov, Evgeniy; Maier, Simon; van Calker, Dietrich; Hochstuhl, Benedikt; Venhoff, Nils; Stich, Oliver; van Elst, Ludger Tebartz

    2016-01-01

    Bipolar disorder (BD) is a severe and lifelong condition. Primary endogenic polygenetic forms are common. Secondary organic forms have received increasing interest recently due to the detection of immunological encephalopathies that mimic various psychiatric syndromes, including BD. However, only limited data about routine findings of cerebrospinal fluid (CSF) analyses in BD are available. Therefore, we investigated the frequency of alterations in the CSF in patients with BD and the association with autoantibodies, cerebral magnetic resonance imaging, and electroencephalography findings. CSF samples of patients with BD collected from January 1998 until December 2015 were analyzed retrospectively. Patients with preexisting causes for alterations in the CSF (e.g., patients with obvious past or current neurological disorders) were excluded. In total, 63 patients with BD fulfilled the inclusion criteria for the study. In 1.6% of the patients with BD, an increased white blood cell count was found in the CSF. Increased albumin quotients were found in 12.9% of the patients, oligoclonal bands (OCBs) in 1.6%, and increased immunoglobulin (Ig) G indices in 3.2% (OCBs were not measured in case of increased IgG indices). No significant differences in CSF findings were found between patients with manic and depressive episodes. The main findings of this open uncontrolled study are that alterations in the CSF may be found in a small, but potentially relevant, subgroup of patients with BD. These findings are discussed in light of the new concepts of mild encephalitis and immunological encephalopathy. The detection of patients with possibly secondary organic bipolar syndromes could open up new causal treatment options with immunomodulatory medication. PMID:28008318

  9. Multivariate analysis of the serum-cerebrospinal fluid-protein-relation for the diagnosis of neurological diseases of the central nervous systems.

    PubMed

    Prosiegel, M; Neu, I S; Pelka, R B; Fateh-Moghadam, A

    1983-12-01

    In a population comprising 197 patients, serum and CSF proteins were assayed using the radial immunodiffusion technique devised by Mancini. Multiple discriminants analysis was applied to investigate whether the measured CSF/serum protein relations and their ratios could be regarded as an indicator of specific neurological diseases. One significant finding was that the slope angle alpha of the regression line between the serum/CSF relation and molecular weight may represent an important indicative parameter. A small angle is suggestive of enhanced permeability of the BBB, a large angle of a correspondingly lowered permeability. Further, the analyses demonstrated that the combined use of several predictors can markedly improve differential diagnosis. The study also demonstrates the potential of a statistical analytic technique that is still rarely applied in medicine.

  10. 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

  11. 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

  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. Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage.

    PubMed

    Wang, Kuo-Chuan; Tang, Sung-Chun; Lee, Jing-Er; Li, Yu-I; Huang, Yi-Shuian; Yang, Wei-Shiung; Jeng, Jiann-Shing; Arumugam, Thiruma V; Tu, Yong-Kwang

    2017-02-01

    We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

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

    PubMed

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

    2010-11-01

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

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

    PubMed

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

    2013-02-01

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

  16. 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.

  17. Cerebrospinal Fluid Steroidomics: Are Bioactive Bile Acids Present in Brain?*

    PubMed Central

    Ogundare, Michael; Theofilopoulos, Spyridon; Lockhart, Andrew; Hall, Leslie J.; Arenas, Ernest; Sjövall, Jan; Brenton, A. Gareth; Wang, Yuqin; Griffiths, William J.

    2010-01-01

    In this study we have profiled the free sterol content of cerebrospinal fluid by a combination of charge tagging and liquid chromatography-tandem mass spectrometry. Surprisingly, the most abundant cholesterol metabolites were found to be C27 and C24 intermediates of the bile acid biosynthetic pathways with structures corresponding to 7α-hydroxy-3-oxocholest-4-en-26-oic acid (7.170 ± 2.826 ng/ml, mean ± S.D., six subjects), 3β-hydroxycholest-5-en-26-oic acid (0.416 ± 0.193 ng/ml), 7α,x-dihydroxy-3-oxocholest-4-en-26-oic acid (1.330 ± 0.543 ng/ml), and 7α-hydroxy-3-oxochol-4-en-24-oic acid (0.172 ± 0.085 ng/ml), and the C26 sterol 7α-hydroxy-26-norcholest-4-ene-3,x-dione (0.204 ± 0.083 ng/ml), where x is an oxygen atom either on the CD rings or more likely on the C-17 side chain. The ability of intermediates of the bile acid biosynthetic pathways to activate the liver X receptors (LXRs) and the farnesoid X receptor was also evaluated. The acidic cholesterol metabolites 3β-hydroxycholest-5-en-26-oic acid and 3β,7α-dihydroxycholest-5-en-26-oic acid were found to activate LXR in a luciferase assay, but the major metabolite identified in this study, i.e. 7α-hydroxy-3-oxocholest-4-en-26-oic acid, was not an LXR ligand. 7α-Hydroxy-3-oxocholest-4-en-26-oic acid is formed from 3β,7α-dihydroxycholest-5-en-26-oic acid in a reaction catalyzed by 3β-hydroxy-Δ5-C27-steroid dehydrogenase (HSD3B7), which may thus represent a deactivation pathway of LXR ligands in brain. Significantly, LXR activation has been found to reduce the symptoms of Alzheimer disease (Fan, J., Donkin, J., and Wellington C. (2009) Biofactors 35, 239–248); thus, cholesterol metabolites may play an important role in the etiology of Alzheimer disease. PMID:19996111

  18. Evaluation of the role hemoglobin in cerebrospinal fluid plays in producing contractions of cerebral arteries.

    PubMed

    White, R P; Macleod, R M; Muhlbauer, M S

    1987-03-01

    Many investigators have concluded that hemoglobin is the spasmogen responsible for cerebral vasospasm. The present study was designed to ascertain whether the contractile responses of isolated canine basilar arteries to xanthochromic cerebrospinal fluid from subarachnoid hemorrhage patients was associated with hemoglobin concentration as measured spectrophotometrically. The results clearly showed that spasmogenicity and hemoglobin content were not correlated. The magnitude and duration of the arterial responses varied greatly, further indicating that more than a single factor was responsible. The potent antagonistic, vasodilator effect of such proteins as antithrombin III may account for some of the variation, but the results directly complement clinical findings of others indicating that hemoglobin is not the singular cause of cerebral vasospasm.

  19. Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

    PubMed Central

    Zhang, Linda W.; Warrington, Junie P.

    2016-01-01

    Magnesium sulfate (MgSO4) is the most widely used therapy in the clinic to prevent the progression of preeclampsia, a hypertensive disorder of pregnancy, to eclampsia. Eclampsia, manifested as unexplained seizures and/or coma during pregnancy or postpartum, accounts for ~13% of maternal deaths worldwide. While MgSO4 continues to be used in the clinic, the mechanisms by which it exerts its protective actions are not well understood. In this study, we tested the hypothesis that MgSO4 protects against placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines. To test this hypothesis, MgSO4 was administered via mini-osmotic pump (60 mg/day, i.p.) to pregnant and placental ischemic rats, induced by mechanical reduction of uterine perfusion pressure, from gestational day 14–19. This treatment regimen of MgSO4 led to therapeutic level of 2.8 ± 0.6 mmol/L Mg in plasma. MgSO4 had no effect on improving placental ischemia-induced changes in mean arterial pressure, number of live fetuses, or fetal and placental weight. Placental ischemia increased, while MgSO4 prevented the increase in water content in the anterior cerebrum. Cytokine and chemokine levels were measured in the cerebrospinal fluid using a multi-plex assay. Results demonstrate that cerebrospinal fluid, obtained via the cisterna magna, had reduced protein, albumin, interleukin (IL)-17A, IL-18, IL-2, eotaxin, fractalkine, interferon gamma, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-2 following MgSO4 treatment. These data support the hypothesis that MgSO4 offers neuroprotection by preventing placental ischemia-induced cerebral edema and reducing levels of cytokines/chemokines in the cerebrospinal fluid. PMID:28008305

  20. Effects of blood contamination and the rostro-caudal gradient on the human cerebrospinal fluid proteome.

    PubMed

    Aasebø, Elise; Opsahl, Jill Anette; Bjørlykke, Yngvild; Myhr, Kjell-Morten; Kroksveen, Ann Cathrine; Berven, Frode S

    2014-01-01

    Over the last years there has been an increased focus on the importance of knowing the effect of pre-analytical influence on the proteomes under study, particularly in the field of biomarker discovery. We present three proteomics studies examining the effect of blood contamination and the rostro-caudal gradient (RCG) on the cerebrospinal fluid (CSF) proteome, in addition to plasma/CSF protein ratios. The studies showed that the central nervous system (CNS) derived proteins appeared to be unaffected by the RCG, while the plasma-derived proteins showed an increase in concentration towards the lumbar area. This implies that the concentration of the plasma-derived proteins in CSF will vary depending on the volume of CSF that is collected. In the CSF samples spiked with blood, 262 of 814 quantified proteins showed an abundance increase of more than 1.5 fold, while 403 proteins had a fold change of less than 1.2 and appeared to be unaffected by blood contamination. Proteins with a high plasma/CSF ratio appeared to give the largest effect on the CSF proteome upon blood contamination. The results give important background information on how factors like blood contamination, RCG and blood-CNS-barrier influences the CSF proteome. This information is particularly important in the field of biomarker discovery, but also for routine clinical measurements. The data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange with identifier PXD000401.

  1. Cerebrospinal Fluid Leak in Cochlear Implantation: Enlarged Cochlear versus Enlarged Vestibular Aqueduct (Common Cavity Excluded)

    PubMed Central

    Polizzi, Valeria; Formigoni, Patrizia; Russo, Carmela; Tribi, Lorenzo

    2016-01-01

    Objective. To share our experience of cerebrospinal fluid gusher in cochlear implantation in patients with enlarged cochlear or vestibular aqueduct. Study Design. Case series with comparison and a review of the literature. Methods. A retrospective study was performed. Demographic and radiological results of patients with enlarged cochlear aqueduct or enlarged vestibular aqueduct in 278 consecutive cochlear implant recipients, including children and adults, were evaluated between January 2000 and December 2015. Results. Six patients with enlarged cochlear aqueduct and eight patients with enlarged vestibular aqueduct were identified. Cerebrospinal fluid gusher occurs in five subjects with enlarged cochlear aqueduct and in only one case of enlarged vestibular aqueduct. Conclusion. Based on these findings, enlarged cochlear aqueduct may be the best risk predictor of cerebrospinal fluid gusher at cochleostomy during cochlear implant surgery despite enlarged vestibular aqueduct. PMID:27847516

  2. 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

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

    PubMed Central

    Koh, Lena; Zakharov, Andrei; Johnston, Miles

    2005-01-01

    In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system. The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption. PMID:16174293

  4. 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

  5. The Effect of rFVIIa on Pro- and Anti-Inflamatory Cytokines in Serum and Cerebrospinal Fluid in a Swine Model of Traumatic Brain Injury

    DTIC Science & Technology

    2011-01-01

    alpha expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature. Neurosurgery ...Short Communication The effect of rFVIIa on pro- and anti-inflamatory cytokines in serum and cerebrospinal fluid in a swine model of traumatic brain...Tumor necrosis factor-ex lnterleukin-1 p lnterleukin-1 0 rfVlla TBl Twenty anesthetized immature Yorkshire swine underwent fluid percussion TBI. At

  6. 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

  7. Automated assay of gamma-aminobutyric acid in human cerebrospinal fluid.

    PubMed

    Böhlen, P; Schechter, P J; van Damme, W; Coquillat, G; Dosch, J C; Koch-Weser, J

    1978-02-01

    We describe an automated amino acid analyzer with fluorescence detection (o-phthalaldehyde) which permits sensitive and rapid determinations of gamma aminobutyric acid in human cerebrospinal fluid. Concentrations as low as 50 nmol/liter can be accurately determined in 100 mul samples at the rate of one sample per hour. Concentrations in untreated cerebrospinal fluid increase rapidly after sampling by lumbar puncture. The concentration in immediately deproteinized samples from 38 patients with intervertebral disc disorders was 220 +/- 81 nmol/liter (mean +/- SD).

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

    PubMed

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

    2017-01-01

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

  9. Effect of nitazoxanide on albendazole pharmacokinetics in cerebrospinal fluid and plasma in rats.

    PubMed

    Ruiz-Olmedo, María Isabel; González-Hernández, Iliana; Palomares-Alonso, Francisca; Franco-Pérez, Javier; González F, María de Lourdes; Jung-Cook, Helgi

    2017-03-01

    Background: Although albendazole is the drug-of-choice for the treatment of neurocysticercosis, its efficacy is limited due to its low bioavailability. An alternative for optimizing pharmacological treatment is through drug combinations. In vitro studies have shown that nitazoxanide and tizoxanide (the active metabolite of nitazoxanide) exhibit cysticidal activity and that the combination of tizoxanide with albendazole sulfoxide (the active metabolite of albendazole) produced an additive effect. Objectives: (1) To assess the concentration profile of tizoxanide in plasma and in cerebrospinal fluid; and (2) to evaluate the influence of nitazoxanide on the pharmacokinetics of albendazole in plasma and in cerebrospinal fluid. Methods: Two different studies were conducted. In study 1, 10 male Sprague-Dawley rats received a single oral dose of 7.5 mg/kg of nitazoxanide and serial blood and cerebrospinal fluid samples were collected over a period of 4 h. In study 2, 38 healthy male Sprague-Dawley rats were randomly divided into two groups: one of these received a single dose of albendazole (15 mg/kg) and, in the other group, albendazole (15 mg/kg) was co-administered with nitazoxanide (7.5 mg/kg). Plasma and cerebrospinal fluid samples were collected from 0 to 16 h after administration. Albendazole sulfoxide and tizoxanide levels were assayed by using HPLC or LC/MS techniques. Results: In study 1, tizoxanide reached a maximum plasma concentration of 244.42 ± 31.98 ng/mL at 0.25 h; however, in cerebrospinal fluid, this could be detected only at 0.5 h, and levels were below the quantification limit (10 ng/mL). These data indicate low permeation of tizoxanide into the blood brain barrier. In study 2, Cmax, the area under the curve, and the mean residence time of albendazole sulfoxide in plasma and cerebrospinal fluid were not affected by co-administration with nitazoxanide. Conclusion: The results of the present study indicate that in rats at the applied doses

  10. Exosomal proteome analysis of cerebrospinal fluid detects biosignatures of neuromyelitis optica and multiple sclerosis.

    PubMed

    Lee, Jingyun; McKinney, Kimberly Q; Pavlopoulos, Antonis J; Han, May H; Kim, Su-Hyun; Kim, Ho Jin; Hwang, Sunil

    2016-11-01

    Quantitative proteomic analysis of exosomes isolated from cerebrospinal fluid (CSF) of neuromyelitis optica (NMO) patients detected signature proteins differentiating NMO from multiple sclerosis (MS) and idiopathic longitudinally extensive transverse myelitis. Exosomes with good yields were obtained using ultracentrifugation from pooled CSF assisted by chemokine-based clustering strategy, which improved target molecule identification by providing amplified fold change values. 442 significant proteins generated a list of signature molecules of diseases validated primarily by the identification of known markers such as glial fibrillary acidic protein (GFAP) and fibronectin specific to NMO and MS respectively. MetaCore pathway analysis of significant proteins supported the involvement of these proteins in disease progression via neurological pathway. Expression levels of target molecules from orthogonal label-free quantification employing quadrupole-Orbitrap hybrid mass spectrometry were in good agreement with those from Western blotting. Additional investigation of GFAP and fibronectin as representative disease molecules revealed their presence in intact exosomes as detected by flow cytometry. This comprehensive study suggests that the exosomal proteomic analysis of CSF can be applied to the identification and characterization of inflammatory disorders of the central nervous system.

  11. A fast and reproducible method for albumin isolation and depletion from serum and cerebrospinal fluid.

    PubMed

    Holewinski, Ronald J; Jin, Zhicheng; Powell, Matthew J; Maust, Matthew D; Van Eyk, Jennifer E

    2013-03-01

    Analysis of serum and plasma proteomes is a common approach for biomarker discovery, and the removal of high-abundant proteins, such as albumin and immunoglobins, is usually the first step in the analysis. However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker subproteome itself. The first goal of this study was to test a new commercially available affinity capture reagent from Protea Biosciences and to compare the efficiency and reproducibility to four other commercially available albumin depletion methods. The second goal of this study was to determine if there is a highly efficient albumin depletion/isolation system that minimizes sample handling and would be suitable for large numbers of samples. Two of the methods tested (Sigma and ProteaPrep) showed an albumin depletion efficiency of 97% or greater for both serum and cerebrospinal fluid (CSF). Isolated serum and CSF albuminomes from ProteaPrep spin columns were analyzed directly by LC-MS/MS, identifying 128 serum (45 not previously reported) and 94 CSF albuminome proteins (17 unique to the CSF albuminome). Serum albuminome was also isolated using Vivapure anti-HSA columns for comparison, identifying 105 proteins, 81 of which overlapped with the ProteaPrep method.

  12. Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study.

    PubMed

    Frank, L Matthew; Shinnar, Shlomo; Hesdorffer, Dale C; Shinnar, Ruth C; Pellock, John M; Gallentine, William; Nordli, Douglas R; Epstein, Leon G; Moshé, Solomon L; Lewis, Darrell V; Sun, Shumei

    2012-12-01

    This prospective multicenter study of 200 patients with fever-associated status epilepticus (FSE), of whom 136 underwent a nontraumatic lumbar puncture, confirms that FSE rarely causes cerebrospinal fluid (CSF) pleocytosis. CSF glucose and protein levels were unremarkable. Temperature, age, seizure focality, and seizure duration did not affect results. CSF pleocytosis should not be attributed to FSE.

  13. 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

  14. A Novel Rapidly Growing Mycobacterium Species Causing an Abdominal Cerebrospinal Fluid Pseudocyst Infection

    PubMed Central

    Hussain, Cory K.; de Man, Tom J. B.; Toney, Nadege C.; Kamboj, Kamal; Balada-Llasat, Joan-Miquel; Wang, Shu-Hua

    2016-01-01

    Nontuberculous mycobacteria (NTM) are a rare cause of ventriculoperitoneal shunt infections. We describe the isolation and identification of a novel, rapidly growing, nonpigmented NTM from an abdominal cerebrospinal fluid pseudocyst. The patient presented with fevers, nausea, and abdominal pain and clinically improved after shunt removal. NTM identification was performed by amplicon and whole-genome sequencing. PMID:27704004

  15. 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...

  16. Indices of free radical activity in the cerebrospinal fluid in motor neuron disease.

    PubMed Central

    Mitchell, J D; Jackson, M J; Pentland, B

    1987-01-01

    Indices of free-radical activity and lipid peroxidation were studied in cerebrospinal fluid samples obtained from 11 patients with motor neuron disease and 11 reference subjects. No differences were found between the two groups. The significance of this finding is discussed in relation to current views of the possible pathogenesis of this disease. PMID:3625217

  17. 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

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

    PubMed Central

    Holmes, Courtney; Sharabi, Yehonatan

    2012-01-01

    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

  19. 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

  20. Management of Persistent Cerebrospinal Fluid Leakage Following Thoraco-lumbar Surgery

    PubMed Central

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

    2012-01-01

    Study Design This was a retrospective study of patients who had developed a dural tear after thoracic and lumbar spine surgery that was not recognized during the surgery, and was treated either by lumbar drainage or over-sewing of the wounds. Purpose To revisit the treatment strategies in postoperative dural leaks and present our experience with over-sewing of the wound and lumbar drainage. Overview of Literature Unintended durotomy is a frequent complication of spinal surgery. Management of subsequent cerebrospinal fluid leakage remains controversial. There is no distinct treatment guideline according to the etiology in the current literature. Methods The records of 368 consecutive patients who underwent thoracic and/or lumbar spine surgery from 2006 throug h 2010 were retrospectively reviewed. Seven cerebrospinal fluid fistulas and five pseudomeningoceles were noted in 12 (3.2%) procedures. Cerebrospinal fluid diversion by lumbar drainage in five pseudomeningoceles and over-sewing of wounds in seven cerebrospinal fluid fistulas employed in 12 patients. Clinical grading was evaluated by Wang. Results Of the 12 patients who had a dural tear, 5 were managed successfully with lumbar drainage, and 7 with oversewing of the wound. The clinical outcomes were excellent in 9 patients, good in 2, and poor in 1. Complications such as neurological deficits, or superficial or deep wound infections did not develop. A recurrence of the fistula or pseudomeningocele after the treatment was not seen in any of our patients. Conclusions Pseudomeningoceles respond well to lumbar drainage, whereas over-sewing of the wound is an alternative treatment option in cerebrospinal fluid fistulas without neurological compromise. PMID:22977694

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

    PubMed

    Stoop, Marcel P; Rosenling, Therese; Attali, Amos; Meesters, Roland J W; Stingl, Christoph; Dekker, Lennard J; van Aken, Hans; Suidgeest, Ernst; Hintzen, Rogier Q; Tuinstra, Tinka; van Gool, Alain; Luider, Theo M; Bischoff, Rainer

    2012-08-03

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of neurological symptoms, and proteomics analysis was performed using nano-LC-Orbitrap mass spectrometry. Additionally, the minocycline concentration in CSF was determined using quantitative matrix-assisted laser desorption/ionization-triple-quadrupole tandem mass spectrometry (MALDI-MS/MS) in the selected reaction monitoring (SRM) mode. Fifty percent of the minocycline-treated EAE animals did not show neurological symptoms on day 14 ("responders"), while the other half displayed neurological symptoms ("nonresponders"), indicating that minocycline delayed disease onset and attenuated disease severity in some, but not all, animals. Neither CSF nor plasma minocycline concentrations correlated with the onset of symptoms or disease severity. Analysis of the proteomics data resulted in a list of 20 differentially abundant proteins between the untreated animals and the responder group of animals. Two of these proteins, complement C3 and carboxypeptidase B2, were validated by quantitative LC-MS/MS in the SRM mode. Differences in the CSF proteome between untreated EAE animals and minocycline-treated responders were similar to the differences between minocycline-treated responders and nonresponders (70% overlap). Six proteins that remained unchanged in the minocycline-treated animals but were elevated in untreated EAE animals may be related to the mechanism of action of minocycline.

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

    PubMed Central

    Chang, Jessica T.; Lehtinen, Maria K.

    2015-01-01

    ABSTRACT 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. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 75–92, 2016 PMID:25980532

  3. 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

  4. 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.

  5. Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia.

    PubMed

    Skillbäck, Tobias; Farahmand, Bahman Y; Rosén, Christoffer; Mattsson, Niklas; Nägga, Katarina; Kilander, Lena; Religa, Dorota; Wimo, Anders; Winblad, Bengt; Schott, Jonathan M; Blennow, Kaj; Eriksdotter, Maria; Zetterberg, Henrik

    2015-09-01

    Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with

  6. Chromogranin A immunoreactivity in human cerebrospinal fluid: properties, relationship to noradrenergic neuronal activity, and variation in neurologic disease.

    PubMed

    O'Connor, D T; Cervenka, J H; Stone, R A; Parmer, R J; Franco-Bourland, R E; Madrazo, I; Langlais, P J

    1993-10-01

    Although measurement of chromogranin A in the bloodstream is of value in sympathoadrenal investigations, little is systematically known about chromogranin A in cerebrospinal fluid, despite substantial knowledge about its occurrence and distribution in brain. We therefore applied a homologous human chromogranin A radioimmunoassay to cerebrospinal fluid, in order to evaluate the properties and stability of cerebrospinal fluid chomogranin A, as well as its relationship to central noradrenergic neuronal activity, to peripheral (plasma) chromogranin A, and to disease states such as hypertension, renal failure and Parkinsonism. Authentic, physically stable chromogranin A immunoreactivity was found in cerebrospinal fluid (at 37-146 ng/ml; mean, 87.0 +/- 6.0 ng/ml in healthy subjects), and several lines of evidence (including 3.39 +/- 0.27-fold higher chromogranin A in cerebrospinal fluid than in plasma) indicated that it originated from a local central nervous system source, rather than the periphery. Cerebrospinal fluid chromogranin A values were not influenced by administration of effective antihypertensive doses of clonidine or propranolol, and were not related to the cerebrospinal fluid concentrations of norepinephrine, methoxyhydroxyphenylglycol, or dopamine-beta-hydroxylase; thus, cerebrospinal fluid chromogranin A was not closely linked to biochemical or pharmacologic indices of central noradrenergic neuronal activity. Cerebrospinal fluid chromogranin A was not changed (P > 0.1) in essential hypertension (84.2 +/- 14.0 ng/ml) or renal failure (72.2 +/- 13.4 ng/ml), despite a marked (7.1-fold; P < 0.001) increase in plasma chromogranin A in renal failure, and a modest (1.5-fold; P = 0.004) increase in plasma chromogranin A in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. 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

  8. Higher level of NT-proCNP in cerebrospinal fluid of patients with meningitis.

    PubMed

    Tomasiuk, Ryszard; Lipowski, Dariusz; Szlufik, Stanislaw; Peplinska, Krystyna; Mikaszewska-Sokolewicz, Malgorzata

    2016-02-12

    Aminoterminal pro-C type natriuretic peptide (NT-proCNP) as an active form of CNP, has been recently proven to be a potential marker of sepsis and to be linked to inflammatory diseases. So far, there are no studies describing the level of NT-proCNP in meningitis. The purpose of this study was to evaluate the diagnostic value of NT-proCNP in cerebrospinal fluid (CSF) in patients with meningitis and to compare it with the serum level of CRP and procalcitonin (PCT) in this group of patients. The results were compared to serum levels of CRP, PCT and CSF levels of cytosis, protein and lactate. NT-proCNP levels were statistically significant between the control group and the meningitis groups (p=0.02; R=0.3). We also noted a correlation between the level of NT-proCNP in the CSF of all of the study groups (controls and meningitis patients) and the CSF levels of cytosis (p<0.5; R=0.43), protein (p<0.05; R=0.39) and lactate (p<0.05; R=0.34), and also the serum level of CRP (p<0.05; R=0.30), but not serum PCT (p>0.05; R=0.11). These results suggest that NT-proCNP could be a potential marker of meningitis, but it cannot be used to distinguish between the types of meningitis.

  9. 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.

  10. Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid

    PubMed Central

    Hashemi, Elham; Sadeghi, Yousef; Aliaghaei, Abbas; Seddighi, Afsoun; Piryaei, Abbas; Broujeni, Mehdi Eskandarian; Shaerzadeh, Fatemeh; Amini, Abdollah; Pouriran, Ramin

    2017-01-01

    As the key producer of cerebrospinal fluid (CSF), the choroid plexus (CP) provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2), as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP) in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic) led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions. PMID:28250752

  11. Quantitative analysis of cerebrospinal fluid brain derived neurotrophic factor in the patients with multiple sclerosis.

    PubMed

    Mashayekhi, Farhad; Salehi, Zivar; Jamalzadeh, Hamid Reza

    2012-01-01

    Multiple sclerosis (MS) is the most common cause ofnontraumatic neurological disability in Europe and North America. Growth factor expression could participate in the repair process of the demyelinating disease. Among growth factors, brain derived neurotrophic factors (BDNF) has been demonstrated to play an important role in neuronal and axonal survival. In the central nervous system (CNS), neurons are the main source of BDNF. Another potential source are activated astrocytes, which are present in inflamed areas in the CNS as shown in MS. In this study, total protein concentration (TPC) and BDNF levels in the cerebrospinal fluid (CSF) samples from the patients with MS (n = 48) and control subjects (n = 53) were measured using a Bio-Rad protein assay and enzyme linked immunosorbent assay (ELISA). No significant change in the CSF TPC of patients with MS was seen as compared to normal CSF. The presence of BDNF in the CSF samples was shown by Western blot. Using ELISA, it was shown that the level of BDNF in the MS CSF is higher than in normal CSF. It is concluded that BDNF is a constant component of human CSF. Moreover, it could be implicated in the pathophysiology of MS.

  12. Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients

    PubMed Central

    Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

    2016-01-01

    The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrPSc) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly. PMID:27852982

  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. Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease.

    PubMed

    Rodrigues, Filipe Brogueira; Byrne, Lauren; McColgan, Peter; Robertson, Nicola; Tabrizi, Sarah J; Leavitt, Blair R; Zetterberg, Henrik; Wild, Edward J

    2016-10-01

    Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre-symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale '99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme-linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p < 0.05. Seventy-six participants were included in this cross-sectional multicenter international pilot study. Age-adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p = 0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r = -0.29, p = 0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r = 0.32, p = 0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age-adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of

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

    PubMed

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

    2012-03-01

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

  16. Successful reversal of immediate paraplegia associated with repair of acute Type A aortic dissection using cerebrospinal fluid drainage.

    PubMed

    Shimura, Shinichiro; Cho, Yasunori; Aki, Akira; Ueda, Toshihiko

    2013-12-01

    We present a case of a 49-year old man who suffered from immediate paraplegia upon awakening from anaesthesia after surgery for acute aortic dissection Type A. A catheter was promptly inserted into the spinal canal for cerebrospinal fluid drainage, and the cerebrospinal fluid pressure was maintained <10 cmH2O. Although magnetic resonance imaging showed extensive spinal cord ischaemia, the patient gradually recovered from the paraplegia and was able to walk by himself after rehabilitation. In some cases, cerebrospinal fluid drainage can be effective for the treatment of immediate postoperative spinal cord damage.

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

    PubMed

    Sherwood, James A; Brittain, David C; Howard, John J; Oliver, JoAnne

    2015-08-01

    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.

  19. Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics

    PubMed Central

    2014-01-01

    Background Alzheimer’s disease (AD) is the leading cause of dementia affecting greater than 26 million people worldwide. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau181 are well established as diagnostic biomarkers of AD, there is a need for additional CSF biomarkers of neuronal function that continue to change during disease progression and could be used as pharmacodynamic measures in clinical trials. Multiple proteomic discovery experiments have reported a range of CSF biomarkers that differ between AD and control subjects. These potential biomarkers represent multiple aspects of the disease pathology. The performance of these markers has not been compared with each other, and their performance has not been evaluated longitudinally. Results We developed a targeted-proteomic, multiple reaction monitoring (MRM) assay for the absolute quantitation of 39 peptides corresponding to 30 proteins. We evaluated the candidate biomarkers in longitudinal CSF samples collected from aged, cognitively-normal control (n = 10), MCI (n = 5), and AD (n = 45) individuals (age > 60 years). We evaluated each biomarker for diagnostic sensitivity, longitudinal consistency, and compared with CSF Aβ42, tau, and p-tau181. Four of 28 quantifiable CSF proteins were significantly different between aged, cognitively-normal controls and AD subjects including chitinase-3-like protein 1, reproducing published results. Four CSF markers demonstrated significant longitudinal change in AD: Amyloid precursor protein, Neuronal pentraxin receptor, NrCAM and Chromogranin A. Robust correlations were observed within some subgroups of proteins including the potential disease progression markers. Conclusion Using a targeted proteomics approach, we confirmed previous findings for a subset of markers, defined longitudinal performance of our panel of markers, and established a flexible proteomics method for robust multiplexed analyses. PMID:24902845

  20. 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

  1. Value of cerebrospinal fluid α-synuclein species as biomarker in Parkinson's diagnosis and prognosis.

    PubMed

    Parnetti, Lucilla; Cicognola, Claudia; Eusebi, Paolo; Chiasserini, Davide

    2016-01-01

    Since diagnosis of Parkinson's disease (PD) is mostly based on clinical criteria, it is almost impossible to formulate an early diagnosis, as well as a timely differential diagnosis versus other parkinsonisms. A great effort in searching reliable biomarkers both for early diagnosis and prognosis in PD is currently ongoing. Cerebrospinal fluid has been widely investigated as potential source for such biomarkers, with particular emphasis on α-synuclein (α-syn) species. We reviewed all the clinical studies carried out so far on cerebrospinal fluid quantification of α-syn species in PD. Current evidence supports the value of total and oligomeric α-syn in PD diagnosis and in the differential diagnosis of PD and other parkinsonisms. Conversely, the role of α-syn species in PD prognosis remains unsatisfactory.

  2. 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.

  3. 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.

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

    PubMed

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

    2015-11-10

    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.

  5. Fluorescent Gold Nanoclusters for Selective Detection of Dopamine in Cerebrospinal fluid

    PubMed Central

    Govindaraju, Saravanan; Ankireddy, Seshadri Reddy; Viswanath, Buddolla; Kim, Jongsung; Yun, Kyusik

    2017-01-01

    Since the last two decades, protein conjugated fluorescent gold nanoclusters (NCs) owe much attention in the field of medical and nanobiotechnology due to their excellent photo stability characteristics. In this paper, we reported stable, nontoxic and red fluorescent emission BSA-Au NCs for selective detection of L-dopamine (DA) in cerebrospinal fluid (CSF). The evolution was probed by various instrumental techniques such as UV-vis spectroscopy, High resolution transmission electron microscopy (HTEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), photoluminescence spectroscopy (PL). The synthesised BSA-Au NCs were showing 4–6 nm with high fluorescent ~8% Quantum yield (QY). The fluorescence intensity of BSA-Au NCs was quenched upon the addition of various concentrations of DA via an electron transfer mechanism. The decrease in BSA-Au NCs fluorescence intensity made it possible to determine DA in PBS buffer and the spiked DA in CSF in the linear range from 0 to 10 nM with the limit of detection (LOD) 0.622 and 0.830 nM respectively. Best of our knowledge, as-prepared BSA-Au NCs will gain possible strategy and good platform for biosensor, drug discovery, and rapid disease diagnosis such as Parkinson’s and Alzheimer diseases. PMID:28067307

  6. Super-Resolution Microscopy of Cerebrospinal Fluid Biomarkers as a Tool for Alzheimer's Disease Diagnostics.

    PubMed

    Zhang, William I; Antonios, Gregory; Rabano, Alberto; Bayer, Thomas A; Schneider, Anja; Rizzoli, Silvio O

    2015-01-01

    Alzheimer's disease (AD) is neuropathologically characterized by aggregates of amyloid-β peptides (Aβ) and tau proteins. The consensus in the AD field is that Aβ and tau should serve as diagnostic biomarkers for AD. However, their aggregates have been difficult to investigate by conventional fluorescence microscopy, since their size is below the diffraction limit (∼200 nm). To solve this, we turned to a super-resolution imaging technique, stimulated emission depletion (STED) microscopy, which has a high enough precision to allow the discrimination of low- and high-molecular weight aggregates prepared in vitro. We used STED to analyze the structural organization of Aβ and tau in cerebrospinal fluid (CSF) from 36 AD patients, 11 patients with mild cognitive impairment (MCI), and 21 controls. We measured the numbers of aggregates in the CSF samples, and the aggregate sizes and intensities. These parameters enabled us to distinguish AD patients from controls with a specificity of ∼87% and a sensitivity of ∼79% . In addition, the aggregate parameters determined with STED microscopy correlated with the severity of cognitive impairment in AD patients. Finally, these parameters may be useful as predictive tools for MCI cases. The STED parameters of two MCI patients who developed AD during the course of the study, as well as of MCI patients whose Aβ ELISA values fall within the accepted range for AD, placed them close to the AD averages. We suggest that super-resolution imaging is a promising tool for AD diagnostics.

  7. Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

    PubMed Central

    Meeter, Lieke H.H.; Patzke, Holger; Loewen, Gordon; Dopper, Elise G.P.; Pijnenburg, Yolande A.L.; van Minkelen, Rick; van Swieten, John C.

    2016-01-01

    Background Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials. PMID:27703466

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

    PubMed

    Danč, Ladislav; Bodor, Róbert; Troška, Peter; Horčičiak, Michal; Masár, Marián

    2014-08-01

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

  9. 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.

  10. Identification of a Biomarker in Cerebrospinal Fluid for Neuronopathic Forms of Gaucher Disease

    PubMed Central

    Zigdon, Hila; Savidor, Alon; Levin, Yishai; Meshcheriakova, Anna; Schiffmann, Raphael; Futerman, Anthony H.

    2015-01-01

    Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available. PMID:25775479

  11. 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.

  12. Glioblastoma multiforme with epithelial differentiation: a potential diagnostic pitfall in cerebrospinal fluid cytology.

    PubMed

    Gill, Simpal K; Padmanabhan, Vijayalakshmi; Hickey, William F; Marotti, Jonathan D

    2015-08-01

    Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear-cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient's recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation.

  13. Metastatic Signet-Ring Cell Carcinoma of the Bladder in Cerebrospinal Fluid.

    PubMed

    Lin, Diana Murro; Park, Ji-Weon; Gattuso, Paolo

    2017-01-01

    Primary bladder signet-ring cell carcinoma (SRCC) is extremely rare and associated with an aggressive course. To our knowledge, we describe the first metastatic bladder SRCC identified in cerebrospinal fluid (CSF). A 68-year-old male with 1 year history of primary bladder SRCC with spinal metastasis presented with multiple falls and loss of consciousness. Brain imaging showed high signal in the frontoparietal sulci and superior cerebellum. CSF analysis was significant for increased leukocytes with monocyte predominance while protein and glucose values were within normal range. There was a hypercellular population of pleomorphic tumor cells with signet-ring morphology, similar to those seen in his diagnostic bladder biopsies. The signet-ring cells were positive for cytokeratin 7 and 20 and negative for CDX-2 and prostate-specific antigen. The patient's clinical condition rapidly deteriorated and he died less than a week after presentation. At autopsy, brain sections revealed signet ring cells in the meninges overlying the cerebrum, cerebellum, brainstem, spinal cord, and pituitary with superficial invasion of the brain parenchyma. No brain parenchymal lesions were present. This case illustrates a unique complication of primary bladder SRCC. Diagn. Cytopathol. 2017;45:73-76. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    Rostgaard, Nina; Waldemar, Gunhild; Nielsen, Jørgen Erik; Simonsen, Anja Hviid

    2015-01-01

    As dementia is a fast-growing health care problem, it is becoming an increasingly urgent need to provide an early diagnosis in order to offer patients the best medical treatment and care. Validated biomarkers which reflect the pathology and disease progression are essential for diagnosis and are important when developing new therapies. Today, the core protein biomarkers amyloid-β42, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However, the biomarkers have proved insufficient predictors of dementias with a different pathology, e.g. frontotemporal dementia (FTD); furthermore, the biomarkers are not useful for early AD diagnosis. Familial dementias with a known disease-causing mutation can be extremely valuable to study; yet the biomarker profiles in patients with familial dementias are not clear. This review summarizes CSF biomarker findings from studies on symptomatic and presymptomatic individuals carrying a mutation in one of the genes known to cause early-onset familial AD or FTD. In conclusion, the biomarker profile of inherited AD is quite similar between carriers of different mutations as well as similar to the profile found in sporadic AD, whereas familial FTD does not seem to have a clear biomarker profile. Hence, new biomarkers are needed for FTD.

  15. 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

    2016-01-06

    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.

  16. Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer Disease in South Korea

    PubMed Central

    Chae, Won Seok; Kim, Hyeong Jun; Shin, Ho Sik; Kim, Saeromi; Im, Ji Young; Ahn, Sang Il; Min, Kyoung Dae; Yim, Soo Jae; Ye, Byoung Seok; Seo, Sang Won; Jeong, Jee Hyang; Park, Kyung Won; Choi, Seong Hye; Na, Duk L.

    2017-01-01

    Laboratory-specific reference values for cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers are necessary. Our objective was to apply well-known CSF biomarkers and redetermine their diagnostic cutoff values for AD in South Korea. CSF samples from matched control subjects (n=71), patients with AD dementia (ADD, n=76), and other neurological disorders with cognitive decline (OND, n=47) were obtained from 6 Korean dementia clinics according to a standardized protocol. CSF biomarker concentrations were measured using enzyme-linked immunosorbent assay. CSF biomarkers differed significantly between the ADD and control groups (P<0.001 for all), and between the ADD and OND groups (P<0.001 for all). The areas under the curve in differentiation of ADD from control subjects were 0.97 for Aβ42, 0.93 for total tau (tTau), 0.86 for pTau, and 0.99 for both tTau/Aβ42 and pTau/Aβ42 ratios. Our revised cutoff value for Aβ42 was higher than our previous one, whereas the values for the Tau proteins were similar. The tTau/Aβ42 ratio had the highest accuracy, 97%. Our findings highlight the usefulness of CSF AD biomarkers in South Korea, and the necessity of continually testing the reliability of cutoff values. PMID:28030437

  17. 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

  18. Value of a single-shot turbo spin-echo pulse sequence for assessing the architecture of the subarachnoid space and the constitutive nature of cerebrospinal fluid.

    PubMed

    Pease, Anthony; Sullivan, Stacey; Olby, Natasha; Galano, Heather; Cerda-Gonzalez, Sophia; Robertson, Ian D; Gavin, Patrick; Thrall, Donald

    2006-01-01

    Three case history reports are presented to illustrate the value of the single-shot turbo spin-echo pulse sequence for assessment of the subarachnoid space. The use of the single-shot turbo spin-echo pulse sequence, which is a heavily T2-weighted sequence, allows for a rapid, noninvasive evaluation of the subarachnoid space by using the high signal from cerebrospinal fluid. This sequence can be completed in seconds rather than the several minutes required for a T2-fast spin-echo sequence. Unlike the standard T2-fast spin-echo sequence, a single-shot turbo spin-echo pulse sequence also provides qualitative information about the protein and the cellular content of the cerebrospinal fluid, such as in patients with inflammatory debris or hemorrhage in the cerebrospinal fluid. Although the resolution of the single-shot turbo spin-echo pulse sequence images is relatively poor compared with more conventional sequences, the qualitative information about the subarachnoid space and cerebrospinal fluid and the rapid acquisition time, make it a useful sequence to include in standard protocols of spinal magnetic resonance imaging.

  19. A Multicenter, Randomized Controlled Trial of Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury

    DTIC Science & Technology

    2015-10-01

    purpose of this randomized clinical trial is to evaluate the safety and efficacy of cerebrospinal fluid drainage (CSFD) and to provide a preliminary... clinical efficacy evaluation of the combination of CSFD and elevation of mean arterial pressure (MAP) in patients with acute spinal cord injury...and society that are expected to increase with better long term care technologies. The purpose of this randomized clinical trial is to evaluate the

  20. Viral immunoblotting: a sensitive method for detecting viral-specific oliogoclonal bands in unconcentrated cerebrospinal fluid.

    PubMed

    Moyle, S; Keir, G; Thompson, E J

    1984-06-01

    A new method for detecting viral antibodies in cerebrospinal fluid is described. The technique has many advantages over previously published methods in that it is highly sensitive eliminating the need to concentrate the CSF, takes 5 h to complete, avoids the use of radionucleides, and most importantly circumvents problems associated with prozone effects which occur in immunoprecipitation reaction since the viral antigen is immobilized on nitrocellulose membranes.

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

    PubMed Central

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

    2014-01-01

    Measurements of the activities of lysosomal enzymes in cerebrospinal fluid have recently been proposed as putative biomarkers for Parkinson's disease and other synucleinopathies. To define the operating procedures useful for ensuring the reliability of these measurements, we analyzed several pre-analytical factors that may influence the activity of β-glucocerebrosidase, α-mannosidase, β-mannosidase, β-galactosidase, α-fucosidase, β-hexosaminidase, cathepsin D and cathepsin E in cerebrospinal fluid. Lysosomal enzyme activities were measured by well-established fluorimetric assays in a consecutive series of patients (n = 28) with different neurological conditions, including Parkinson's disease. The precision, pre-storage and storage conditions, and freeze/thaw cycles were evaluated. All of the assays showed within- and between-run variabilities below 10%. At −20°C, only cathepsin D was stable up to 40 weeks. At −80°C, the cathepsin D, cathepsin E, and β-mannosidase activities did not change significantly up to 40 weeks, while β-glucocerebrosidase activity was stable up to 32 weeks. The β-galactosidase and α-fucosidase activities significantly increased (+54.9±38.08% after 4 weeks and +88.94±36.19% after 16 weeks, respectively). Up to four freeze/thaw cycles did not significantly affect the activities of cathepsins D and E. The β-glucocerebrosidase activity showed a slight decrease (−14.6%) after two freeze/thaw cycles. The measurement of lysosomal enzyme activities in cerebrospinal fluid is reliable and reproducible if pre-analytical factors are accurately taken into consideration. Therefore, the analytical recommendations that ensue from this study may contribute to the establishment of actual values for the activities of cerebrospinal fluid lysosomal enzymes as putative biomarkers for Parkinson's disease and other neurodegenerative disorders. PMID:24983953

  2. [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.

  3. 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

  4. Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid.

    PubMed

    Ben-Menachem, E; Persson, L I; Mumford, J; Haegele, K D; Huebert, N

    1991-01-01

    Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of gamma-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (+/- SD) reduction of seizure frequency was 65% +/- 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation.

  5. The application of cerebrospinal fluid biomarkers in early diagnosis of Alzheimer disease.

    PubMed

    Blennow, Kaj; Zetterberg, Henrik

    2013-05-01

    This article gives an updated account of the clinical application of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD). The clinically most relevant biomarkers, total tau, phospho-tau and Aβ42 are discussed, and how they may be used, together with other diagnostic investigations, to make a predementia diagnosis of AD. Recent findings in sporadic and genetic preclinical AD are also discussed and, more specifically, what the biomarkers have taught us on the sequence of events in the pathogenic process underlying AD.

  6. [Cells in the cerebrospinal fluid of dogs and cats. Part 2].

    PubMed

    Grevel, V; Machus, B

    1992-02-01

    Three groups of cerebrospinal fluid (CSF) cells can be formed: 1. cells of the normal CSF, such as monocytes, small lymphocytes and occasionally cells of the ventricle system, 2. cells found in dogs and cats with neurologic disorders, such as reactive monocytes and lymphocytes, macrophages, neutrophils and eosinophils in addition to cells of the first group, 3. neoplastic cells. The different cells are introduced and their origin, function and occurrence are discussed. Mitotic figures, degenerated cells and artefacts are also mentioned.

  7. Vancomycin Cerebrospinal Fluid Pharmacokinetics in Children with Cerebral Ventricular Shunt Infections

    PubMed Central

    Autmizguine, Julie; Moran, Cassie; Gonzalez, Daniel; Capparelli, Edmund V.; Smith, P. Brian; Grant, Gerald A; Benjamin, Daniel K.; Cohen-Wolkowiez, Michael; Watt, Kevin M

    2014-01-01

    This study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection. Vancomycin CSF concentrations ranged from 0.06 to 9.13 mg/L and the CSF: plasma ratio ranged from 0 to 0.66. Two children out of three with a staphylococcal CSF infection had CSF concentrations > minimal inhibitory concentration at the end of the dosing interval. PMID:24776517

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

    PubMed

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

    2016-10-01

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

  9. Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica

    PubMed Central

    Kariya, Yoshinobu; Kariya, Yukiko; Saito, Toshie; Nishiyama, Shuhei; Honda, Takashi; Tanaka, Keiko; Yoshida, Mari; Fujihara, Kazuo; Hashimoto, Yasuhiro

    2015-01-01

    Background Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and spinal cord. Although NMO has long been considered a subtype of multiple sclerosis (MS), the effects of interferon-β treatment are different between NMO and MS. Recent findings of NMO-IgG suggest that NMO could be a distinct disease rather than a subtype of MS. However, the underlying molecular mechanism of NMO pathology remains poorly understood. Methods OPN in the cerebrospinal fluid and brain of patients with NMO and with MS, as well as of patients with other neurologic disease/idiopathic other neurologic disease was examined using Western blotting, ELISA, immunohistochemistry and Boyden chamber. Results Here we show that osteopontin is significantly increased in the cerebrospinal fluid of NMO patients compared with MS patients. Immunohistochemical analyses revealed that osteopontin was markedly elevated in the cerebral white matter of NMO patients and produced by astrocytes, neurons, and oligodendroglia as well as infiltrating macrophages. We also demonstrate that the interaction of the cerebrospinal fluid osteopontin in NMO patients with integrin αvβ3 promoted macrophage chemotaxis by activating phosphoinositide 3-kinase and MEK1/2 signaling pathways. Conclusion These results indicate that osteopontin is involved in NMO pathology. General significance Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO. PMID:26673877

  10. 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.

  11. MicroRNAs in Cerebrospinal Fluid as Potential Biomarkers for Parkinson's Disease and Multiple System Atrophy.

    PubMed

    Marques, Tainá M; Kuiperij, H Bea; Bruinsma, Ilona B; van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Bloem, Bas R; Verbeek, Marcel M

    2016-11-14

    Parkinson's disease (PD) and multiple system atrophy (MSA) are both part of the spectrum of neurodegenerative movement disorders and α-synucleinopathies with overlap of symptoms especially at early stages of the disease but with distinct disease progression and responses to dopaminergic treatment. Therefore, having biomarkers that specifically classify patients, which could discriminate PD from MSA, would be very useful. MicroRNAs (miRNAs) regulate protein translation and are observed in biological fluids, including cerebrospinal fluid (CSF), and may therefore have potential as biomarkers of disease. The aim of our study was to determine if miRNAs in CSF could be used as biomarkers for either PD or MSA. Using quantitative PCR (qPCR), we evaluated expression levels of 10 miRNAs in CSF patient samples from PD (n = 28), MSA (n = 17), and non-neurological controls (n = 28). We identified two miRNAs (miR-24 and miR-205) that distinguished PD from controls and four miRNAs that differentiated MSA from controls (miR-19a, miR-19b, miR-24, and miR-34c). Combinations of miRNAs accurately discriminated either PD (area under the curve (AUC) = 0.96) or MSA (AUC = 0.86) from controls. In MSA, we also observed that miR-24 and miR-148b correlated with cerebellar ataxia symptoms, suggesting that these miRNAs are involved in cerebellar degeneration in MSA. Our findings support the potential of miRNA panels as biomarkers for movement disorders and may provide more insights into the pathological mechanisms related to these disorders.

  12. Choroid plexus carcinoma cells in the cerebrospinal fluid of a Staffordshire Bull Terrier.

    PubMed

    Pastorello, Alice; Constantino-Casas, Fernando; Archer, Joy

    2010-12-01

    An 11-year-old female intact Staffordshire Bull Terrier was referred to the Queen's Veterinary School Hospital at the University of Cambridge with sudden onset of episodic behavioral changes, a mammary mass, and papilledema in the right eye. On physical examination the dog appeared depressed and had a head tilt to the right with anisocoria. Using magnetic resonance imaging, a broad-based lesion that obliterated the fourth ventricle was detected in the right brainstem. There was no evidence of pulmonary metastasis. Cerebrospinal fluid (CSF) was then obtained; fluid analysis showed an increased cell count (165 cells/μL, reference interval 0-7 cells/μL) and total protein (0.30 g/L, reference value <0.25 g/L). Cytologic evaluation revealed a population of atypical epithelial cells arranged in cohesive rafts and characterized by moderate to occasionally marked anisocytosis and anisokaryosis. The appearance was highly suspicious of a malignant epithelial neoplasm. The dog was euthanized and on postmortem examination an asymmetrical nonencapsulated cerebellar mass was found within the choroid plexus of the fourth ventricle with local extension into the cerebellopontine angle. Histologic sections of the cerebellar mass contained arborizing papillary structures covered by a single layer of atypical epithelial cells that showed local infiltration into the adjacent neuropil. The diagnosis was choroid plexus carcinoma. The atypical epithelial cells were negative for pancytokeratin and strongly positive for vimentin. The finding of clusters of choroid plexus epithelial cells in the CSF demonstrates the value of utilizing a relatively noninvasive diagnostic technique for diagnosis of choroid plexus tumors.

  13. Application of Control Volume Analysis to Cerebrospinal Fluid Dynamics

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

  14. Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

    PubMed Central

    2009-01-01

    Background The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF HIV-1 viral load and HIV-1 plasma viral load; and (3) CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. Methods Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006). We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche). Data were processed with Statistix 7.0 software (linear regression analysis). Results Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01). No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123). Conclusion Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

  15. Cerebrospinal Fluid Aβ42 Levels and APP Processing Pathway Genes in Parkinson’s Disease

    PubMed Central

    Bekris, L.M.; Tsuang, D.W.; Peskind, E.R.; Yu, C.E.; Montine, T.J.; Zhang, J.; Zabetian, C.P.; Leverenz, J.B.

    2015-01-01

    Background Of recent interest is the finding that certain CSF biomarkers traditionally linked to Alzheimer’s disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine if genetic variation within the amyloid precursor protein (APP) processing pathway genes, correlate with cerebrospinal fluid (CSF) Aβ42 levels in Parkinson’s disease (PD). Method PD (n=86) and control (n=161) DNA were genotyped for 19 regulatory region tagging single nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN and APH1B) involved in the cleavage of APP. SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, gender, and APOE ε4 status. Results Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484 and rs2040273 and PSEN1 rs362344). Conclusion The results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ε4 non-carriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared to other neurodegenerative diseases, such as AD, are warranted. PMID:25808939

  16. Cerebrospinal fluid flow imaging by using phase-contrast MR technique

    PubMed Central

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

    2011-01-01

    Cerebrospinal fluid (CSF) spaces include ventricles and cerebral and spinal subarachnoid spaces. CSF motion is a combined effect of CSF production rate and superimposed cardiac pulsations. Knowledge of CSF dynamics has benefited considerably from the development of phase-contrast (PC) MRI. There are several disorders such as communicating and non-communicating hydrocephalus, Chiari malformation, syringomyelic cyst and arachnoid cyst that can change the CSF dynamics. The aims of this pictorial review are to outline the PC MRI technique, CSF physiology and cerebrospinal space anatomy, to describe a group of congenital and acquired disorders that can alter the CSF dynamics, and to assess the use of PC MRI in the assessment of various central nervous system abnormalities. PMID:21586507

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

    PubMed

    Csako, Gyorgy

    2012-01-01

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

  18. In-depth Characterization of the Cerebrospinal Fluid (CSF) Proteome Displayed Through the CSF Proteome Resource (CSF-PR)*

    PubMed Central

    Guldbrandsen, Astrid; Vethe, Heidrun; Farag, Yehia; Oveland, Eystein; Garberg, Hilde; Berle, Magnus; Myhr, Kjell-Morten; Opsahl, Jill A.; Barsnes, Harald; Berven, Frode S.

    2014-01-01

    In this study, the human cerebrospinal fluid (CSF) proteome was mapped using three different strategies prior to Orbitrap LC-MS/MS analysis: SDS-PAGE and mixed mode reversed phase-anion exchange for mapping the global CSF proteome, and hydrazide-based glycopeptide capture for mapping glycopeptides. A maximal protein set of 3081 proteins (28,811 peptide sequences) was identified, of which 520 were identified as glycoproteins from the glycopeptide enrichment strategy, including 1121 glycopeptides and their glycosylation sites. To our knowledge, this is the largest number of identified proteins and glycopeptides reported for CSF, including 417 glycosylation sites not previously reported. From parallel plasma samples, we identified 1050 proteins (9739 peptide sequences). An overlap of 877 proteins was found between the two body fluids, whereas 2204 proteins were identified only in CSF and 173 only in plasma. All mapping results are freely available via the new CSF Proteome Resource (http://probe.uib.no/csf-pr), which can be used to navigate the CSF proteome and help guide the selection of signature peptides in targeted quantitative proteomics. PMID:25038066

  19. Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency.

    PubMed

    O'Connor, D T; Cervenka, J H; Stone, R A; Levine, G L; Parmer, R J; Franco-Bourland, R E; Madrazo, I; Langlais, P J; Robertson, D; Biaggioni, I

    1994-02-01

    1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely

  20. Cerebrospinal fluid white cell count: discriminatory or otherwise for enteroviral meningitis in infants and young children?

    PubMed

    Tan, Natalie Woon Hui; Lee, Elis Yuexian; Khoo, Gloria Mei Chin; Tee, Nancy Wen Sim; Krishnamoorthy, Subramania; Choong, Chew Thye

    2016-04-01

    Non-polio enteroviruses (EV) are the most common viruses causing aseptic meningitis in children. We aim to evaluate the cerebrospinal fluid (CSF) characteristics of neonates and children with EV meningitis with a view to determine whether it could be discriminatory or otherwise in making a positive diagnosis. We performed a 3-year (July 2008-July 2011) retrospective study of children ≤16 years, treated at a tertiary children's hospital, with positive CSF EV polymerase chain reaction (PCR) and negative blood and CSF bacterial cultures. A total of 206 children were studied. The median CSF white cell count was 79 cells/mm(3) (range 0-4608 cells/mm(3)). CSF pleocytosis was observed in 99/150 (66%) aged ≤90 days, 3/4 (75%) aged 90 days-1 year, and 49/52 (94%) children ≥3 years. There was a huge variability in CSF pleocytosis in infants ≤90 days, where 34% of them had no pleocytosis, while in 66%, a wide range of pleocytosis that might even suggest bacterial meningitis was noted. CSF red cells were low, and protein or sugar values were not discriminatory. CSF pleocytosis in relation to increasing age was found to be statistically significant (p < 0.001). Early lumbar puncture within 48 h of symptoms and absence of CSF pleocytosis was also statistically significant (p = 0.039). CSF pleocytosis in EV meningitis is commoner in older children. As there was a huge variability in CSF pleocytosis in infants ≤90 days particularly, CSF analysis including EV PCR could avoid unnecessary antibiotic therapy.

  1. Activin a release into cerebrospinal fluid in a subset of patients with severe traumatic brain injury.

    PubMed

    Phillips, David J; Nguyen, Phuong; Adamides, Alexios A; Bye, Nicole; Rosenfeld, Jeffrey V; Kossmann, Thomas; Vallance, Shirley; Murray, Lynnette; Morganti-Kossmann, Maria C

    2006-09-01

    Activin A is a member of the transforming growth factor-beta superfamily and has been demonstrated to be elevated during inflammation and to have neuroprotective properties following neural insults. In this study, we examined whether traumatic brain injury (TBI) induced a response in activin A or in the concentrations of its binding protein, follistatin. Thirty-nine patients with severe TBI had daily, matched cerebrospinal fluid (CSF) and serum samples collected post-TBI and these were assayed for activin A and follistatin using specific immunoassays. Concentrations of both molecules were assessed relative to a variety of clinical parameters, such as the Glasgow Coma Score, computer tomography classification of TBI, measurement of injury markers, cell metabolism and membrane breakdown products. In about half of the patients, there was a notable increase in CSF activin A concentrations in the first few days post-TBI. There were only minor perturbations in either serum activin or in either CSF or serum follistatin concentrations. The CSF activin A response was not related to any of the common TBI indices, but was strongly correlated with two common markers of brain damage, neuronal specific enolase and S100-beta. Further, activin A levels were also associated with indices of metabolism, such as lactate and pyruvate, excitotoxicity (glutamate) and membrane lipid breakdown products such as glycerol. In one of the two patients who developed a CSF infection, activin A concentrations in CSF became markedly elevated. Thus, some TBI patients have an early release of activin A into the CSF that may result from activation of inflammatory and/or neuroprotective pathways.

  2. Cytotoxicity of ventricular cerebrospinal fluid from Parkinson patients: correlation with clinical profiles and neurochemistry.

    PubMed

    Mandybur, George T; Miyagi, Yasushi; Yin, Wei; Perkins, Eddie; Zhang, John H

    2003-01-01

    Other investigators have reported that the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) might contain endogenous dystrophic factors. Using CSF samples drawn from individual PD patients during surgery, we investigated the toxic effect of ventricular CSF (vCSF) on the growth of PC12 cells and the correlation between the clinical profiles of the patients and CSF neurochemistry. Ventricular CSF samples from 28 patients with PD or essential tremor (ET) were collected during ventriculography for stereotactic pallidotomy or thalamotomy. PC12 cells were incubated with 20% vCSF from both clinical groups for up to 72 h. Microdialysis was used to analyze four neurochemical parameters (glucose, lactate, pyruvate, and glutamate) in each vCSF sample. We observed that vCSF drawn from PD patients exerted nonspecific growth inhibition on PC12 cells in a time-dependent manner. The growth inhibitory action of PD-vCSF decreased significantly after heat treatment. Microdialysis demonstrated no statistical differences between PD and ET samples among the four parameters studied. In addition, PC12 cell survival after 72 h incubation with PD-vCSF correlated with no neurochemical parameter or individual clinical profile (age, onset age, duration of disease, Hoehn & Yahr stage, disease progression rate), except for a slight correlation between vCSF and disease progression rate in heat treated samples from female patients. One or more endogenous cytotoxic factors in PD-vCSF inhibit PC12 cell growth. This factor or factors are partially sensitive to heat which suggests proteins or peptides as possible agents. The cytotoxic effect of PD-vCSF did not directly correlate with any clinical profiles studied or energy metabolism of PD brain.

  3. [Beta amyloid in blood and cerebrospinal fluid is associated with high density lipoproteins].

    PubMed

    Kudinova, N V; Kudinov, A R; Berezov, T T

    1996-01-01

    Cerebrovascular and parenchymal amyloid deposits found in brains of Alzheimer's disease, Down's syndrome and normal aging are mainly composed of aggregated amyloid beta protein (A beta), a unique peptide 39 to 44 amino acids long. A similar but soluble A beta (s A beta) has been identified in plasma, cerebrospinal fluid (CSF) and cell supernatants, indicating that it is a normal protein. We report here that s A beta in normal human plasma and CSF is complexed to high density lipoprotein (HDL) 3 and very high density lipoprotein (VHDL). Biotinylated synthetic peptide A beta 1-40 was traced in normal human plasma in in vitro experiments. Both tracer biotin-labeled A beta 1-40 and native s A beta were specifically recovered in HDL3 and VHDL as it was assessed in immunoprecipitation experiments of purified plasma lipoproteins and lipoprotein depleted plasma. This fact prompted us to ascertain whether the interaction of s A beta with HDL does occur in normal human CSF in vivo. For this purpose normals human CSF was fractionated by means of sequential flotation ultracentrifugation. The presence of s A beta in the resulting lipoprotein fractions as well as in the lipoprotein depleted CSF was analysed by immunoblot analysis, electron and immune-electron microscopy and native size exclusion chromatography. Immunoblot analysis with 6E10 monoclonal anti-A beta antibodies revealed s A beta association with all HDL subspecies of CSF, primarily HDL3 and VHDL and immunoelectron microscopy confirmed an association of s A beta with CSF-HDL particles of 16.8 + 3.2 nm. Native size exclusion chromatography followed by immunoblot analysis with antibodies against A beta and different apoliproproteins indicated an association of s A beta with HDL complexes of approximately 200 kDa molecular weight. Soluble A beta association with HDL3 and VHDL may be involved in maintaining the solubility of A beta in biological fluids and points to a possible role of lipoproteins and lipoprotein lipid

  4. Three dimensional modeling of the cerebrospinal fluid dynamics and brain interactions in the aqueduct of sylvius.

    PubMed

    Fin, Loïc; Grebe, Reinhard

    2003-06-01

    A computational fluid dynamics (CFD) method is presented to investigate the flow of cerebro-spinal fluid (CSF) in the cerebral aqueduct. In addition to former approaches exhibiting a rigid geometry, we propose a model which includes a deformable membrane as the wall of this flow channel. An anatomical shape of the aqueduct was computed from magnetic resonance images (MRI) and the resulting meshing was immersed in a marker-and-cell (MAC) staggered grid for to take into account fluid-structure interactions. The time derivatives were digitized using the Crank-Nicolson scheme. The equation of continuity was modified by introducing an artificial compressibility and digitized by a finite difference scheme. Calculations were validated with the simulation of laminar flow in a rigid tube. Then, comparisons were made between simulations of a rigid aqueduct and a deformable one. We found that the deformability of the walls has a strong influence on the pressure drop for a given flow.

  5. Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls.

    PubMed

    Bendix, Marie; Uvnäs-Moberg, Kerstin; Petersson, Maria; Kaldo, Viktor; Åsberg, Marie; Jokinen, Jussi

    2017-03-23

    Mental disorders and related behaviors such as suicidality and violence have been associated to dysregulation of e g carbohydrate metabolism. We hypothesized that patients after suicide attempt, compared to healthy controls, would have higher insulin and lower glucagon levels in plasma and cerebrospinal fluid and that these changes would be associated to violent behavior. Twenty-eight medication-free patients (10 women, 18 men), hospitalized after suicide attempt, and 19 healthy controls (7 women, 12 men) were recruited with the aim to study risk factors for suicidal behavior. Psychological/psychiatric assessment was performed with SCID I and II or the SCID interview for healthy volunteers respectively, the Karolinska Interpersonal Violence Scale (KIVS) for assessment of lifetime violence expression behavior, the Montgomery-Åsberg-Depression-Scale (MADRS) and the Comprehensive Psychological Rating Scale (CPRS) for symptomatic assessment of depression and appetite. Fasting levels of insulin and glucagon were measured in plasma (P) and cerebrospinal fluid (CSF). Suicide attempters had higher insulin- and lower glucagon-levels in plasma- and CSF compared to controls. Except for P-glucagon these associations remained significant after adjusting for age and/or BMI. Patients reported significantly more expressed interpersonal violence compared to healthy volunteers. Expressed violence was significantly positively correlated with P- and CSF-insulin and showed a significant negative correlation with P-glucagon in study participants. These findings confirm and extend prior reports that higher insulin and lower glucagon levels in plasma and cerebrospinal fluid are associated with suicidal behavior pointing towards a potential autonomic dysregulation in the control of insulin and glucagon secretion in suicidal patients.

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

    PubMed

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

    2014-03-01

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

  7. Cerebrospinal Fluid Orexin A Levels and Autonomic Function in Kleine-Levin Syndrome

    PubMed Central

    Wang, Jing Yu; Han, Fang; Dong, Song X.; Li, Jing; An, Pei; Zhang, Xiao Zhe; Chang, Yuan; Zhao, Long; Zhang, Xue Li; Liu, Ya Nan; Yan, Han; Li, Qing Hua; Hu, Yan; Lv, Chang Jun; Gao, Zhan Cheng; Strohl, Kingman P.

    2016-01-01

    Study Objectives: Kleine-Levin syndrome (KLS) is a rare disorder of relapsing sleepiness. The hypothesis was that the syndrome is related to a change in the vigilance peptide orexin A. Methods: From 2002 to 2013, 57 patients with relapsing hypersomnolence were clinically assessed in a referral academic center in Beijing, China, and 44 (28 males and 16 females; mean age 18.3 ± 8.9 y (mean ± standard deviation, range 9–57 y) were determined to have clinical and behavioral criteria consistent with KLS. Cerebrospinal fluid orexin A levels and diurnal blood pressure were measured in relapse versus remission in a subgroup of patients. Results: Presenting symptoms included relapsing or remitting excessive sleepiness–associated parallel complaints of cognitive changes (82%), eating disorders (84%); depression (45%); irritability (36%); hypersexuality (18%); and compulsions (11%). Episodes were 8.2 ± 3.3 days in duration. In relapse, diurnal values for blood pressure and heart rate were lower (P < 0.001). In a subgroup (n = 34), cerebrospinal fluid orexin A levels were ∼31% lower in a relapse versus remission (215.7 ± 81.5 versus 319.2 ± 95.92 pg/ml, P < 0.001); in three patients a pattern of lower levels during subsequent relapses was documented. Conclusions: There are lower orexin A levels in the symptomatic phase than in remission and a fall and rise in blood pressure and heart rate, suggesting a role for orexin dysregulation in KLS pathophysiology. Citation: Wang JY, Han F, Dong SX, Li J, An P, Zhang XZ, Chang Y, Zhao L, Zhang XL, Liu YN, Yan H, Li QH, Hu Y, Lv CJ, Gao ZC, Strohl KP. Cerebrospinal fluid orexin A levels and autonomic function in Kleine-Levin syndrome. SLEEP 2016;39(4):855–860. PMID:26943469

  8. Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array

    PubMed Central

    Baird, Geoffrey S.; Nelson, Sally K.; Keeney, Tracy R.; Stewart, Alex; Williams, Stephen; Kraemer, Stephan; Peskind, Elaine R.; Montine, Thomas J.

    2012-01-01

    An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome. PMID:22122984

  9. A lateral flow assay (LFA) for the rapid detection of extraparenchymal neurocysticercosis using cerebrospinal fluid.

    PubMed

    Fleury, Agnes; Sastre, Patricia; Sciutto, Edda; Correia, Silvia; Monedero, Alejandro; Toledo, Andrea; Hernandez, Maricela; Harrison, Leslie J S; Parkhouse, R Michael E

    2016-10-27

    A lateral flow assay (LFA) for the diagnosis and monitoring of extraparenchymal neurocysticercosis, has been developed. The assay is based on the use of the monoclonal antibody HP10, and when applied to cerebrospinal fluid, correctly identified 34 cases of active extraparenchymal neurocysticercosis, but was negative with 26 samples from treated and cured neurocysticercosis patients and with 20 samples from unrelated neurological diseases. There was complete agreement between the HP10 Ag-ELISA results and the HP10-LFA. The HP10-LFA thus has utility for diagnosis and treatment of extraparenchymal neurocysticercosis, frequently a more dangerous form of the infection.

  10. [Idiopathic intracranial hypertension and spontaneous cerebrospinal fluid fistula. Usefulness of intracranial pressure monitoring].

    PubMed

    Horcajadas Almansa, Angel; Román Cutillas, Ana; Jorques Infante, Ana; Ruiz Gómez, José; Busquier, Heriberto

    Spontaneous cerebrospinal fluid (CSF) fistulas are rather common in daily practice. The aim of the surgical treatment is closure of the leak, but recurrences are quite frequent. The association between spontaneous CSF fistulas and idiopathic intracranial hypertension (IIH) is not uncommon, and this is probably the cause of the low rate of success of the surgical treatment. Symptoms of IIH associated with spontaneous CSF fistula are atypical, and diagnosis is often missed. Continuous intracranial pressure monitoring is very useful in the diagnosis of chronic IIH and in patients with spontaneous CSF fistula, as it helps in making decisions on the treatment of these patients.

  11. The use of cerebrospinal fluid and neuropathological studies in neuropsychiatry practice and research

    PubMed Central

    Kansal, Kalyani; Irwin, David J.

    2015-01-01

    Synopsis The gold standard for diagnosis of neurodegenerative diseases (i.e. Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Dementia with Lewy bodies, Amyotrophic lateral sclerosis) is neuropathological examination at autopsy. As such, laboratory studies play a central role in ante mortem diagnosis of these conditions and their differentiation from the neuroinflammatory, infectious, toxic, and other non-degenerative etiologies (e.g. rapidly-progressive dementias) that are encountered in neuropsychiatric practice. This review summarizes the use of cerebrospinal fluid (CSF) laboratory studies in the diagnostic evaluation of dementia syndromes and emerging CSF biomarkers specific for underlying neuropathology in neurodegenerative disease research. PMID:25998118

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

    SciTech Connect

    Vecsei, L.; Csala, B.; Widerloev, E.E.; Ekman, R.; Czopf, J.; Palffy, G. )

    1990-09-01

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

  13. Negative correlation between cerebrospinal fluid FGF21 levels and BDI scores in male Chinese subjects.

    PubMed

    Liu, Yanlong; Wang, Meiling; Tan, Xiaohua; Wang, Xiaofang; Yang, Xiaoyu; Xiao, Jian; Li, Xiaokun; Wang, Fan

    2017-01-27

    Fibroblast growth factor 21 (FGF21) is an important metabolic regulator of glucose homeostasis and lipid metabolism. Recently, FGF21 has been shown to play a robust neuroprotective role and act as a mediator of the effects of mood stabilizers. In the present study, we measured the concentration of FGF21 in human cerebrospinal fluid (CSF) and investigated the relationship of FGF21 levels with depression and anxiety emotions. Sixty-seven Chinese volunteers were recruited from Beijing Jishuitan Hospital. A significant negative association was found between CSF FGF21 levels and Beck Depression Inventory (BDI) scores in male subjects. Our findings provide evidence of the role of FGF21 in mood regulation.

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

    PubMed Central

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

    1990-01-01

    Positive contrast cisternography with digital subtraction of fluoroscopy images before computed tomography (CT) was employed in the investigation of eight patients with cerebrospinal fluid (CSF) rhinorrhoea. Fistulae were visualised by preliminary digital subtraction cisternography (DSC) in six patients and in five patients the sites of leakage were confirmed at surgery. Fluoroscopy facilitated interpretation of CT in all the positive studies and in two patients provided information which could not be deduced from CT cisternography (CTC) alone. The combined technique is recommended for the investigation of patients with recurrent and post operative CSF rhinorrhoea and when CTC alone fails to identify the site of leakage. Images PMID:2292701

  15. Gorham-Stout syndrome affecting the temporal bone with cerebrospinal fluid leakage.

    PubMed

    Morimoto, Noriko; Ogiwara, Hideki; Miyazaki, Osamu; Kitamuara, Masayuki; Nishina, Sachiko; Nakazawa, Atsuko; Maekawa, Takanobu; Morota, Nobuhito

    2013-09-01

    Gorham-Stout syndrome is a rare disorder characterized by progressive osteolysis that leads to the disappearance of bone. Lymphvascular proliferation causes the local destruction of bony tissue. Owing to the low incidence of this syndrome, little is known about its etiology or treatment. We present an 11-year-old girl with Gorham-Stout syndrome that involved right petrous apex in temporal bone and upper clivus, which cause intracranial pressure increase and cerebrospinal fluid (CSF) leakage. The patient required surgical repair of CSF leakage by extradural middle fossa approach with temporal fascia flap. Combined treatment with interferon and propranolol prevented the progression of osteolysis.

  16. Biofilm-associated infection: the hidden face of cerebrospinal fluid shunt malfunction.

    PubMed

    Mounier, Roman; Kapandji, Natacha; Birnbaum, Ron; Cook, Fabrice; Rodriguez, Cristophe; Nebbad, Bibba; Lobo, David; Dhonneur, Gilles

    2016-12-01

    Diagnosis of cerebrospinal fluid (CSF) shunt infection is difficult. Growing evidence links this pattern to biofilm-associated infections (BAI). Biofilm may explain the indolent development of the infection, and the poor efficiency of traditional microbiologic methods. We report the case of a patient admitted for hydrocephalus associated to CSF shunt malfunction. None of the clinical, serum, or CSF laboratory findings were in favor of an infectious process. Only scanning electron microscopy (SEM) revealed the presence of biofilm. Hence, despite a broad CSF shunt infection definition, some infections could remain undiagnosed by the traditional approach. This study is the first to provide some direct evidence for bacterial biofilm-associated CSF shunt infection.

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

    PubMed Central

    Piombo, Marianna; Chiarello, Daniela; Corbetto, Marzia; Di Pino, Giovanni; Dicuonzo, Giordano; Angeletti, Silvia; Riva, Elisabetta; De Florio, Lucia; Capone, Fioravante; Di Lazzaro, Vincenzo

    2015-01-01

    A 45-year-old male noticed progressive weakness of the right lower limb with gait disturbance. Over the following months, motor deficits worsened, spreading to the right upper limb. Electromyography showed active denervation in the upper and lower limb muscles. A diagnosis of amyotrophic lateral sclerosis (ALS) was made. About 2 years after symptom onset, gradual improvement occurred. Cerebrospinal fluid analysis performed about 3 years after the beginning of symptoms identified Cronobacter sakazakii. Since no other possible causes were identified, we suggest that an almost completely reversible ALS-like syndrome had been triggered by Cronobacter infection in our immunocompetent patient. PMID:26955334

  18. Serum Levels of Progranulin Do Not Reflect Cerebrospinal Fluid Levels in Neurodegenerative Disease.

    PubMed

    Wilke, Carlo; Gillardon, Frank; Deuschle, Christian; Dubois, Evelyn; Hobert, Markus A; Müller vom Hagen, Jennifer; Krüger, Stefanie; Biskup, Saskia; Blauwendraat, Cornelis; Hruscha, Michael; Kaeser, Stephan A; Heutink, Peter; Maetzler, Walter; Synofzik, Matthis

    2016-01-01

    Altered progranulin levels play a major role in neurodegenerative diseases, like Alzheimer's dementia (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), even in the absence of GRN mutations. Increasing progranulin levels could hereby provide a novel treatment strategy. However, knowledge on progranulin regulation in neurodegenerative diseases remains limited. We here demonstrate that cerebrospinal fluid progranulin levels do not correlate with its serum levels in AD, FTD and ALS, indicating a differential regulation of its central and peripheral levels in neurodegeneration. Blood progranulin levels thus do not reliably predict central nervous progranulin levels and their response to future progranulin-increasing therapeutics.

  19. Evolutionary development of embryonic cerebrospinal fluid composition and regulation: an open research field with implications for brain development and function.

    PubMed

    Bueno, David; Garcia-Fernàndez, Jordi

    2016-03-15

    Within the consolidated field of evolutionary development, there is emerging research on evolutionary aspects of central nervous system development and its implications for adult brain structure and function, including behaviour. The central nervous system is one of the most intriguing systems in complex metazoans, as it controls all body and mind functions. Its failure is responsible for a number of severe and largely incurable diseases, including neurological and neurodegenerative ones. Moreover, the evolution of the nervous system is thought to be a critical step in the adaptive radiation of vertebrates. Brain formation is initiated early during development. Most embryological, genetic and evolutionary studies have focused on brain neurogenesis and regionalisation, including the formation and function of organising centres, and the comparison of homolog gene expression and function among model organisms from different taxa. The architecture of the vertebrate brain primordium also reveals the existence of connected internal cavities, the cephalic vesicles, which in fetuses and adults become the ventricular system of the brain. During embryonic and fetal development, brain cavities and ventricles are filled with a complex, protein-rich fluid called cerebrospinal fluid (CSF). However, CSF has not been widely analysed from either an embryological or evolutionary perspective. Recently, it has been demonstrated in higher vertebrates that embryonic cerebrospinal fluid has key functions in delivering diffusible signals and nutrients 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. Moreover, it has been shown that the composition and homeostasis of CSF are tightly controlled in a time-dependent manner from the closure of the anterior neuropore, just before the initiation of primary neurogenesis, up to the formation of functional choroid plexuses. In

  20. Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

    Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville

    2014-01-01

    Background The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. Objective To investigate the role of soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings. Methods The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results Lumbar CSF levels of sAPPα were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = −0.295, p = 0.003) and lumbar (r = −0.356, p = 0.01) samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure

  1. Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

    PubMed Central

    2015-01-01

    Background Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis. PMID:26040285

  2. Spinal fluid protein revisited: a reappraisal of the biuret procedure.

    PubMed

    Blijenberg, B G; Roetering, H A; Zwang, L; Leijnse, B

    1985-04-01

    In this study our previously described selected method, a biuret procedure with deproteinization, for the determination of spinal fluid protein is thoroughly discussed against the background of the results found with a number of Lowry modifications. The use of various separation techniques, i.e. deproteinization, ultrafiltration and chromatography (HPLC), for protein analysis led to the question as to whether low molecular weight proteins in cerebrospinal fluid play an important role or not with respect to the choice of a selected method for the determination of total protein.

  3. [Experiences with a sedimentation technique for the enrichment of cerebrospinal fluid cells in the dog and cat. Part 1].

    PubMed

    Grevel, V

    1991-10-01

    The differentiation of cells of the cerebrospinal fluid (CSF) gives valuable information about certain neurologic diseases. The sedimentation technique of Sayk modified by Kölmel is introduced and its application described. Cells of 300 samples of CSF from dogs and cats are evaluated. There were very good to reasonable results in 88% (263 of 300) of the samples. A comparison between cell number, morphology and protein content in 150 samples was performed. 90 CSF samples with normal cell count (less than or equal to 5/mm3, determined in the Fuchs-Rosenthal chamber) were compared with the cell yield after sedimentation. In 58% (52 of 90) of the samples more than 200 cells were found, in 13% (12 of 90) more than 800 could be differentiated. The results are compared with those of other methods mentioned in the literature.

  4. Evidence of cellular immune activation in children with opsoclonus-myoclonus: cerebrospinal fluid neopterin.

    PubMed

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

    2004-12-01

    To evaluate cellular immune activation in opsoclonus-myoclonus syndrome, we measured the inflammatory marker neopterin in the cerebrospinal fluid of 16 children with opsoclonus-myoclonus and neuroblastoma, 24 children with opsoclonus-myoclonus but no tumor, and 19 age-matched controls. The mean concentration in opsoclonus-myoclonus was 2.3-fold higher than in controls (P = .008). Neopterin was greatly elevated in four of the most neurologically severe cases, up to 8.3-fold above the highest control level. Thirteen of the 40 children with opsoclonus-myoclonus but no controls had a neopterin concentration >2 SD above the control mean (P = .005). In this high neopterin subgroup, neurologic severity was significantly greater and the duration of neurologic symptoms was less. In 16 children re-examined on immunotherapy, including adrenocorticotropic hormone (ACTH) combination therapy, treatment was associated with a significant reduction in both neopterin and neurologic severity. Neopterin did not differ significantly between the tumor and non-tumor opsoclonus-myoclonus etiologies. No abnormalities of tetrahydrobiopterin were found. Although cerebrospinal fluid neopterin lacked the sensitivity to be a biomarker of disease activity in opsoclonus-myoclonus, elevated concentrations do support a role for T-cell activation and cell-mediated immunity in its pathophysiology.

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

    PubMed Central

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

    2012-01-01

    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil® (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system. PMID:25737700

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

    PubMed

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

    2005-11-01

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

  7. GWAS of cerebrospinal fluid tau levels identifies novel risk variants for Alzheimer’s disease

    PubMed Central

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

    2013-01-01

    Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau) and Aβ42 are established biomarkers for Alzheimer’s Disease (AD), and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n=1,269), identifying three novel genome-wide significant loci for CSF tau and ptau: rs9877502 (P=4.89×10−9 for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (P=1.07×10−8 and P=3.22×10−9 for tau and ptau respectively), located at 9p24.2 within GLIS3 and rs6922617 (P = 3.58×10−8 for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent datasets rs9877502 showed a strong association with risk for AD, tangle pathology and global cognitive decline (P=2.67×10−4, 0.039, 4.86×10−5 respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. PMID:23562540

  8. Cerebrospinal fluid pharmacology: an improved pharmacology approach for chinese herbal medicine research.

    PubMed

    Wu, Yan-Qing; Zhou, Ying-Wu; Qin, Xiu-de; Hua, Sheng-Yu; Zhang, Yu-Lian; Kang, Li-Yuan

    2013-01-01

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

  9. Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

    PubMed Central

    Malone, James P.; Shah, Aarti R.; Gilmore, Petra; Davis, Alan E.; Roe, Catherine M.; Peskind, Elaine R.; Li, Ge; Galasko, Douglas R.; Clark, Christopher M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Morris, John C.; Holtzman, David M.; Townsend, R. Reid; Fagan, Anne M.

    2011-01-01

    Background Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the ‘preclinical’ stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome. Methods and Findings CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85–0.94 95% confidence interval [CI]) and 0.88 (0.81–0.94 CI), respectively. Conclusions Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel

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

    PubMed

    Uldall, Maria; Botfield, Hannah; Jansen-Olesen, Inger; Sinclair, Alexandra; Jensen, Rigmor

    2017-04-03

    Acetazolamide is one of the most widely used drugs for lowering intracranial pressure (ICP) and is believed to reduce cerebrospinal fluid (CSF) secretion via its action on the choroid plexus (CP). In the CP the main driving force for CSF secretion is primarily active transport of Na(+) ions facilitated by the Na/K ATPase. Transmembrane water channels, known as aquaporins (AQP), are also present in the CP and play an important role in the movement of water. In the present study, we investigated the effect of a single dose acetazolamide on the activity of the Na/K ATPase and ICP. Furthermore, we investigated the expression of Na/K ATPase, AQP1 and AQP4 in the CP tissue following acetazolamide treatment. 12 female Sprague Dawley rats were randomized into two groups; one group received 200mg acetazolamide and the other vehicle treatment. All animals were subjected to ICP recordings and the CP tissue was collected for qPCR and western blot analysis. The effect of acetazolamide on the Na/K ATPase activity was evaluated in an in vitro assay of primary CP epithelial cells isolated from rats. Acetazolamide significantly lowered ICP within 10min of injection compared to the vehicle group (P<0.05), reaching a maximum reduction at 55min 66±4% (P<0.00001). Acetazolamide also significantly decreased the activity of the Na/K ATPase in CP epithelial cells compared to vehicle (P=0.0022). Acetazolamide did not change the AQP1, AQP4 or Na/K ATPase mRNA content in the CP tissue. However, we did record an increase in the amount of AQP1 (p=0.0152) and Na/K ATPase (p=0.0411) protein in the membrane fraction of the CP, but not AQP4 (p=0.0649). A single dose of acetazolamide lowers ICP and modulates the CSF secretion pathway in healthy rats - Firstly, by inhibiting the Na/K ATPase to slow the CSF production, secondly, by increasing AQP1 and Na/K ATPase protein in the membrane of the CP epithelial cells.

  11. Inflammatory molecules in Frontotemporal Dementia: cerebrospinal fluid signature of progranulin mutation carriers.

    PubMed

    Galimberti, D; Bonsi, R; Fenoglio, C; Serpente, M; Cioffi, S M G; Fumagalli, G; Arighi, A; Ghezzi, L; Arcaro, M; Mercurio, M; Rotondo, E; Scarpini, E

    2015-10-01

    Mutations in progranulin gene (GRN) are one of the major causes of autosomal dominant Frontotemporal Lobar Degeneration (FTLD). Progranulin displays anti-inflammatory properties and is likely a ligand of Tumor Necrosis Factor (TNF) receptor 2, expressed on microglia. A few cytokines and chemokines are altered in cerebrospinal fluid (CSF) from patients with sporadic FTLD, whereas no information is available in familial cases. We evaluated, through BioPlex, levels of 27 inflammatory molecules, including cytokines, chemokines, and related receptors, in CSF and matched serum, from FTLD patients carrying GRN mutations as compared with sporadic FTLD with no GRN mutations and controls. Mean±SD Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly increased in CSF from sporadic FTLD patients as compared with controls (334.27±151.5 versus 159.7±49pg/ml; P⩽0.05). In GRN mutation carriers versus controls, CSF levels of MCP-1 were unchanged, whereas Interferon-γ-inducible protein-10 (IP-10) levels were increased (809.17±240.0 versus 436.61±202.5pg/ml; P=0.012). In the same group, TNFα and Interleukin (IL)-15 levels were decreased (3.18±1.41 versus 35.68±30.5pg/ml; P=0.013 and 9.34±5.54 versus 19.15±10.03pg/ml; P=0.023, respectively). Conversely, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) levels were decreased in patients, with or without mutations, as compared with controls (4.63±3.30 and 2.58±20 versus 87.57±70pg/ml, respectively; P<0.05). Moreover, IP-10, IL-15 and RANTES CSF levels were not influenced by age, whereas MCP-1 levels increased with age (ρ=0.48; P=0.007). In conclusion, inflammatory de-regulation was observed in both sporadic FTLD and GRN carriers compared to controls, with a specific inflammatory profile for the latter group.

  12. Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System

    PubMed Central

    Takenaka, Akiko; Sato, Hiroki; Ikeda, Fusako; Yoneda, Misako

    2016-01-01

    carnivores, and in many respects, the pathogenesis of CDV infection in animals resembles that of measles virus infection in humans. We successfully generated a recombinant CDV containing the H and P genes from a mouse-adapted neurovirulent strain and expressing EGFP. The recombinant CDV exhibited severe neurovirulence with high mortality, comparable to the parental mouse-adapted strain. The mouse-infectious model could become a useful tool for analyzing CDV infection of the central nervous system subsequent to passing through the blood-cerebrospinal fluid barrier and infectious progression in the target cells in acute disease. PMID:27489268

  13. Cerebrospinal fluid leakage from the umbilicus: Case report and literature review

    PubMed Central

    Dolas, Ilyas; Apaydin, Hasan Ogunc; Yucetas, Seyho Cem; Ucar, Mehmet Davut; Kilinc, Suleyman; Ucler, Necati

    2016-01-01

    Introduction Shunt catheters within the peritoneal cavity have migrated through and perforated almost all the intra-abdominal hollow viscera. An umbilical cerebrospinal fluid fistula following a ventriculoperitoneal shunt is an extremely rare complication. CASE PRESENTATION We report a 8-month-old infant who presented with leak of clear fluid from the umbilicus, seven months after a ventriculoperitoneal shunt operation. We could not see distal tip of the shunt on examination. After the operation, the patient’s follow-up was uneventful. Discussion The direct effect of CSF and VP shunt, such as chronic irrigation, silicon allergy, foreign body reaction, may cause sterile inflammation on the abdominal structures and this inflammation may soften tissue and cause CFS leakage and VP shunt extrusion. Conclusion If the distal tip detected on umbilical region, these patients should be examined frequently for umbilical shunt pathologies, especially infants. PMID:26814999

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

    PubMed

    Chikly, Bruno; Quaghebeur, Jörgen

    2013-07-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. Effect of Cerebrospinal Fluid Modelling on Spherically Convergent Shear Waves during Blunt Head Trauma.

    PubMed

    Madhukar, Amit; Chen, Ying; Ostoja-Starzewski, Martin

    2017-03-14

    The MRI-based computational model, previously validated by tagged MRI and HARP imaging analysis technique on in vivo human brain deformation, is employed to study transient wave dynamics during blunt head trauma. Three different constitutive models are used for the cerebrospinal fluid (CSF): incompressible solid elastic, viscoelastic and fluid-like elastic using an equation of state model. Three impact cases are simulated which indicate that the blunt impacts give rise not only to a fast pressure wave but also to a slow, and potentially much more damaging, shear (distortional) wave that converges spherically towards the brain center. The wave amplification due to spherical geometry is balanced by damping due to tissues' viscoelasticity and the heterogeneous brain structure, suggesting a stochastic competition of these two opposite effects. It is observed that this convergent shear wave is dependent on the constitutive property of the CSF whereas the peak pressure is not as significantly affected.

  17. Membrane-Introduction Mass Spectrometry Analysis of Desflurane, Propofol and Fentanyl in Plasma and Cerebrospinal Fluid for Estimation BBB Properties

    PubMed Central

    Cherebillo, Vyacheslav Yu.; Polegaev, Andrei V.

    2015-01-01

    A possibility to use the Membrane-Introduction Mass Spectrometry (MIMS) with membrane separator interface has evolved into a powerful method for measurement of anaesthetic agents absolute concentration in blood plasma and cerebrospinal fluid for the study of blood-brain barrier (BBB) properties. Recent advanced a new membrane material was used for drug concentration measurement in biologic fluids. A hydrophobic membrane was used in the interface to separate anaesthetic agents from biological fluids: inhalational anaesthetic desflurane,hypnotic propofol, analgesic fentanyl. The selective detection of volatile anesthetic agents in blood does not require long-term sample processing before injecting the sample into mass-spectrometer interface, in contrast to chromatographic methods. Mass-spectrometric interface for the measurement of anaesthetic agent concentration in biological fluids (blood plasma and cerebrospinal fluid) is described. Sampling of biological fluids was performed during balanced inhalational (desflurane, fentanyl) anaesthesia and total intravenous (propofol, fentanyl) anaesthesia. PMID:26412969

  18. Cerebrospinal fluid indices of blood-brain barrier permeability following adrenal-brain transplantation in patients with Parkinson's disease.

    PubMed

    Ahlskog, J E; Tyce, G M; Kelly, P J; van Heerden, J A; Stoddard, S L; Carmichael, S W

    1989-08-01

    Cerebrospinal fluid (CSF) and serum or plasma concentrations of albumin, IgG and carbidopa were measured before and after adrenal-brain transplantation in patients with Parkinson's disease to indirectly assess blood-brain barrier (BBB) integrity. Previous studies in animals have suggested that the BBB is compromised by cerebral transplantation. CSF and plasma levodopa was also measured to permit comparison with the carbidopa values, recognizing that levodopa readily crosses the BBB via facilitated transport. Our patients underwent adrenal-brain transplantation in accordance with the method of Madrazo et al. (I. Madrazo, R. Drucker-Colin, V. Diaz, J. Martinez-Mata, C. Torres, and J. J. Becerril, 1987, N. Engl. J. Med. 316: 831-834) in which adrenal medullary pieces are implanted in the head of the caudate nucleus, in contact with the cerebrospinal fluid. All patients were maintained on oral carbidopa/levodopa therapy after surgery. CSF albumin/serum albumin and CSF IgG/serum IgG ratios were initially elevated above the preoperative baseline 6 weeks after the surgery; however, these values returned to the preoperative baseline by 6 months following the operation in six of seven patients. This suggested that the BBB was sufficiently intact to exclude these larger protein molecules from the CSF of these six patients. On the other hand, exogenously administered carbidopa, which normally is largely excluded from the cerebrospinal fluid by the BBB, was modestly increased in the CSF in four of the five patients in which it was measured. This suggests that the transplant BBB might be partially patent to small molecules for at least 6 months after the surgery. Whether increased passage of carbidopa into CSF and perhaps the transplant is of clinical significance has yet to be determined. Median CSF levodopa did not increase after surgery, probably because a limited defect in the BBB would be likely to be overshadowed by the effects of facilitated transport. CT scans performed

  19. SPARC/osteonectin, an endogenous mechanism for targeting albumin to the blood-cerebrospinal fluid interface during brain development.

    PubMed

    Liddelow, S A; Dziegielewska, K M; Møllgård, K; Phoenix, T N; Temple, S; Vandeberg, J L; Saunders, N R

    2011-10-01

    Specialized populations of choroid plexus epithelial cells have previously been shown to be responsible for the transfer of individual plasma proteins from blood to the cerebrospinal fluid (CSF), contributing to their characteristically high concentrations in CSF of the developing brain. The mechanism of this protein transfer remains elusive. Using a marsupial, Monodelphis domestica, we demonstrate that the albumin-binding protein SPARC (osteonectin/BM-40/culture-shock protein) is present in a subset of choroid plexus epithelial cells from its first appearance, throughout development, and into adulthood. The synthesis of SPARC by the lateral ventricular plexus was confirmed with real-time PCR. The expression level of SPARC was higher in plexuses of younger than older animals. Western blot analysis of the gene product confirmed the quantitative PCR results. The co-localization of SPARC and albumin shown by immunocytochemistry and its cellular location indicate that this glycoprotein may act as a recognition site for albumin. In addition, the numbers of SPARC-immunopositive cells and its expression were responsive to experimental changes of albumin concentration in the blood. It is suggested that SPARC may be one of the molecules that govern the uptake and delivery of proteins from blood to the CSF. The results also confirm that protein transfer across the blood-CSF barrier is developmentally and physiologically regulated.

  20. How yawning switches the default-mode network to the attentional network by activating the cerebrospinal fluid flow.

    PubMed

    Walusinski, Olivier

    2014-03-01

    Yawning is a behavior to which little research has been devoted. However, its purpose has not yet been demonstrated and remains controversial. In this article, we propose a new theory involving the brain network that is functional during the resting state, that is, the default mode network. When this network is active, yawning manifests a process of switching to the attentional system through its capacity to increase circulation of cerebrospinal fluid (CSF), thereby increasing clearance of somnogenic factors (prostaglandin D(2), adenosine, and others) accumulating in the cerebrospinal fluid.

  1. [Determination of beta 2-microglobulin in the serum and cerebrospinal fluid using radial immunodiffusion (comparison with the Elisa Pharmacia method)].

    PubMed

    Králová, E; Novotná, H; Adam, Z

    1993-12-20

    The authors elaborated a method of radial immunodiffusion for assessment of beta 2-microglobulin serum and cerebrospinal fluid levels in patients. The method is based on a modified procedure of staining and decolouration. The antibody produced by USOL Co. which was used for the purpose was not modified. Comparison of 90 sera and 27 cerebrospinal fluid samples where also the reference method ELISA Pharmacia was used revealed almost absolute agreement, the correlation coefficient was 0.98. The method is used for clinical monitoring in patients with myelomas and renal insufficiencies.

  2. Photoperiod affects the cerebrospinal fluid proteome: a comparison between short day- and long day-treated ewes.

    PubMed

    Teixeira-Gomes, A-P; Harichaux, G; Gennetay, D; Skipor, J; Thiery, J-C; Labas, V; Dufourny, L

    2015-10-01

    Photoperiod is the main physical synchronizer of seasonal functions and a key factor in the modulation of molecule access to cerebrospinal fluid (CSF) in animals. Previous work has shown that photoperiod affects the transfer rate of steroids and protein hormones from blood to CSF and modulates choroid plexus tight junction protein content. We hypothesized that the CSF proteome would also be modified by photoperiod. We tested this hypothesis by comparing CSF obtained from the third ventricle of mature, ovariectomized, estradiol-replaced ewes exposed to long day length (LD) or short day length (SD). Variations in CSF protein expression between SD- or LD-treated ewes were studied in pools of CSF collected for 48 h. Proteins were precipitated, concentrated, and included in a polyacrylamide gel without protein fractionation. After in-gel tryptic digestion of total protein samples, we analyzed the resulting peptides by nanoliquid chromatography coupled with high-resolution tandem mass spectrometry (GeLC-MS/MS). Quantitative analysis was performed using 2 methods based on spectral counting and extracted ion chromatograms. Among 103 identified proteins, 41 were differentially expressed between LD and SD ewes (with P < 0.05 and at least a 1.5-fold difference). Of the 41 differentially expressed proteins, 22 were identified by both methods and 19 using extracted ion chromatograms only. Eighteen proteins were more abundant in LD ewes and 23 were more abundant in SD ewes. These proteins are involved in numerous functions including hormone transport, immune system activity, metabolism, and angiogenesis. To confirm proteomic results, 2 proteins, pigment epithelium-derived factor (PEDF) and gelsolin, for each individual sample of CSF collected under SD or LD were analyzed with Western blots. These results suggest an important photoperiod-dependent change in CSF proteome composition. Nevertheless, additional studies are required to assess the role of each protein in seasonal

  3. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.

    PubMed

    Burgos, Kasandra; Malenica, Ivana; Metpally, Raghu; Courtright, Amanda; Rakela, Benjamin; Beach, Thomas; Shill, Holly; Adler, Charles; Sabbagh, Marwan; Villa, Stephen; Tembe, Waibhav; Craig, David; Van Keuren-Jensen, Kendall

    2014-01-01

    The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess

  4. Cerebrospinal-fluid-derived immunoglobulin G of different multiple sclerosis patients shares mutated sequences in complementarity determining regions.

    PubMed

    Singh, Vaibhav; Stoop, Marcel P; Stingl, Christoph; Luitwieler, Ronald L; Dekker, Lennard J; van Duijn, Martijn M; Kreft, Karim L; Luider, Theo M; Hintzen, Rogier Q

    2013-12-01

    B lymphocytes play a pivotal role in multiple sclerosis pathology, possibly via both antibody-dependent and -independent pathways. Intrathecal immunoglobulin G in multiple sclerosis is produced by clonally expanded B-cell populations. Recent studies indicate that the complementarity determining regions of immunoglobulins specific for certain antigens are frequently shared between different individuals. In this study, our main objective was to identify specific proteomic profiles of mutated complementarity determining regions of immunoglobulin G present in multiple sclerosis patients but absent in healthy controls. To achieve this objective, we purified immunoglobulin G from the cerebrospinal fluid of 29 multiple sclerosis patients and 30 healthy controls and separated the corresponding heavy and light chains via SDS-PAGE. Subsequently, bands were excised, trypsinized, and measured with high-resolution mass spectrometry. We sequenced 841 heavy and 771 light chain variable region peptides. We observed 24 heavy and 26 light chain complementarity determining regions that were solely present in a number of multiple sclerosis patients. Using stringent criteria for the identification of common peptides, we found five complementarity determining regions shared in three or more patients and not in controls. Interestingly, one complementarity determining region with a single mutation was found in six patients. Additionally, one other patient carrying a similar complementarity determining region with another mutation was observed. In addition, we found a skew in the κ-to-λ ratio and in the usage of certain variable heavy regions that was previously observed at the transcriptome level. At the protein level, cerebrospinal fluid immunoglobulin G shares common characteristics in the antigen binding region among different multiple sclerosis patients. The indication of a shared fingerprint may indicate common antigens for B-cell activation.

  5. Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

    PubMed Central

    Parkhomenko, Taisiya A.; Doronin, Vasilii B.; Castellazzi, Massimiliano; Padroni, Marina; Pastore, Michela; Buneva, Valentina N.; Granieri, Enrico; Nevinsky, Georgy A.

    2014-01-01

    It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development. PMID:24736683

  6. Comparison of DNA-hydrolyzing antibodies from the cerebrospinal fluid and serum of patients with multiple sclerosis.

    PubMed

    Parkhomenko, Taisiya A; Doronin, Vasilii B; Castellazzi, Massimiliano; Padroni, Marina; Pastore, Michela; Buneva, Valentina N; Granieri, Enrico; Nevinsky, Georgy A

    2014-01-01

    It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.

  7. False-negative cerebrospinal fluid cryptococcal antigen test due to small-colony variants of Cryptococcus neoformans meningitis in a patient with cystopleural shunt.

    PubMed

    To, Kelvin K W; Cheng, Vincent C C; Tang, Bone S F; Fan, Yiu-Wah; Yuen, Kwok-Yung

    2006-01-01

    This is the first report of a small-colony variant Cryptococcus neoformans isolated from the cerebrospinal fluid of a patient with cystopleural shunt associated chronic meningitis. Cryptococcal antigen testing of the cerebrospinal fluid and the serum were both negative. The atypical morphology and the false-negative test may lead to delay of diagnosis and treatment.

  8. Cerebrospinal fluid from patients with amyotrophic lateral sclerosis inhibits sonic hedgehog function

    PubMed Central

    Drannik, Anna; Martin, Joan; Peterson, Randy; Ma, Xiaoxing; Jiang, Fan; Turnbull, John

    2017-01-01

    Sonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS). ALS is a fatal disease characterized by selective loss of motor neurons due to poorly understood mechanisms. Evidence indicates that Shh might play an important role in ALS, and that Shh signaling might be also adversely affected in ALS. Since little is known about the functional status of Shh pathway in patients with ALS, we therefore sought to determine whether Shh protein levels or biological activity in cerebrospinal fluid (CSF) was less in ALS patients than controls, and whether these measures could be correlated with ALS disease severity and disease progression, and with other CSF analytes of biological interest in ALS. Comparing Shh levels in the CSF of normal controls (n = 13), neurological controls (n = 12), and ALS patients (n = 9) measured by ELISA, we found that CSF Shh levels were not different between controls and ALS patients. However, when assessing Shh biological activity in CSF using in vitro cell-based assays, which measure Shh activity as inducible Gli-driven luminescence, we found that in the presence of exogenous recombinant Shh or the Shh agonist, purmorphamine, the inducible activity of CSF was significantly augmented in the control groups as expected, but not in the ALS group, suggesting the presence of an inhibitor of Shh signaling in ALS CSF samples. Since purmorphamine acts on Smoothened, downstream of Shh and its receptor Patched, the inhibitory action is downstream of Smoothened. Our results also demonstrated that while the inhibitory effect of ALS CSF on Shh signaling did not correlate significantly with ALS disease characteristics, the levels of IL-1β and TNF-α did. In

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

    PubMed Central

    Barone, Francesca; Elmi, Alberto; Romagnoli, Noemi; Bacci, Maria Laura

    2016-01-01

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

  10. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

    PubMed Central

    Scheld, W M; Dacey, R G; Winn, H R; Welsh, J E; Jane, J A; Sande, M A

    1980-01-01

    Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increaed in acute pneumococcal meningitis when compared to control, uninfected animals (6.77 +/- 3.52 vs. 0.26 +/- 0.04 mm Hg/microliter per min, P less than 0.001). Similar elevations (8.93 +/- 4.15 mm Hg/microliter per min were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07 +/- 4.68 mm Hg/microliter per min) and had not returned to normal up to 15 d later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/microliter per min) and no "rebound" effect was apparent 24 h later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the bran to compensate for changes in intracranial volume and pressure. PMID:6995482

  11. Longitudinal Metabolite Profiling of Cerebrospinal Fluid in Normal Pressure Hydrocephalus Links Brain Metabolism with Exercise-Induced VEGF Production and Clinical Outcome.

    PubMed

    Huang, He; Yang, Jun; Luciano, Mark; Shriver, Leah P

    2016-07-01

    Idiopathic normal pressure hydrocephalus is a neurological disease caused by abnormal cerebrospinal fluid flow and presents with symptoms such as dementia. Current therapy involves the removal of excess cerebrospinal fluid by shunting. Not all patients respond to this therapy and biomarkers are needed that could facilitate the characterization of patients likely to benefit from this treatment. Here, we measure brain metabolism in normal pressure hydrocephalus patients by performing a novel longitudinal metabolomic profiling study of cerebrospinal fluid. We find that the levels of brain metabolites correlate with clinical parameters, the amount of vascular endothelial growth factor in the cerebrospinal fluid, and environmental stimuli such as exercise. Metabolomic analysis of normal pressure hydrocephalus patients provides insight into changes in brain metabolism that accompany cerebrospinal fluid disorders and may facilitate the development of new biomarkers for this condition.

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

    PubMed Central

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

    2001-01-01

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

 PMID:11124792

  13. Neurocysticercosis: validity of ELISA after storage of whole blood and cerebrospinal fluid on paper.

    PubMed

    Fleury, A; Bouteille, B; Garcia, E; Marquez, C; Preux, P M; Escobedo, F; Sotelo, J; Dumas, M

    2001-09-01

    Cysticercosis is an infestation of Cysticercus cellulosae. When it occurs in the brain, chronic neurological complications can ensue, most commonly seizures. Neurocysticercosis is usually diagnosed by neuroimaging, a technique not available in most endemic countries. Hence immunological tests are valuable for diagnosis and epidemiological surveys. We evaluated the suitability of paper for storing blood and cerebrospinal fluid (CSF) until subsequent testing by enzyme-linked immunosorbent assay (ELISA), by testing whole blood samples on filter paper from 305 patients and CSF samples from 117 patients stored on ordinary white typing paper and on filter paper. Optimal preservation of biological samples is achieved when whole blood is stored on filter paper, CSF on white paper, and when samples are frozen within 1 week after collection. Our results could improve diagnostic capabilities and facilitate epidemiological surveys in endemic countries where immunodiagnostic tests cannot be rapidly performed because of inadequate laboratory infrastructure.

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

    PubMed Central

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

    2012-01-01

    In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF) and plasma in patients with cryptococcal meningitis (CM), we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy-free HIV-infected patients with CM. Samples were obtained at baseline (S1) and at the second (S2) and third (S3) weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died) showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease. PMID:24470944

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

    PubMed

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

    2012-04-27

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

  16. Endoscopic Repair of Frontal Sinus Cerebrospinal Fluid Leaks after Firearm Injuries: Report of Two Cases

    PubMed Central

    Reyes, Camilo; Solares, C. Arturo

    2015-01-01

    Objectives To describe two cases of cerebrospinal fluid (CSF) leak repair after gunshot wound to the head. Design Retrospective review of two cases. Settings A large regional tertiary care facility. Participants Two patients with gunshot wounds to the skull base. Main Outcome Measures Preoperative and postoperative physical and radiologic findings. Results Patients in this series underwent endoscopic surgery, debridement, and repair of CSF leaks after gunshot wounds to the head. To date, the patients are without CSF leak. Conclusions Endoscopic closure of anterior skull base CSF leaks in patients with gunshot wounds can be safe and effective. Treatment should be decided by the severity of neurologic deterioration throughout the emergency period and the existence or absence of associated intracranial lesions. Timing for surgery should be decided with great care and with a multidisciplinary approach. PMID:26251818

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

  18. Blood stained cerebrospinal fluid responsible for false positive reactions of latex particle agglutination tests.

    PubMed Central

    Camargos, P A; Almeida, M S; Filho, G L; Batista, K W; Carvalho, A G; Pereira, C L

    1994-01-01

    The accuracy of the latex particle agglutination test (LPAT) was assessed in blood stained cerebrospinal fluid (CSF) specimens from 166 paediatric patients, aged from three months to 13 years. A commercial LPAT kit was used to detect Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis A, B, and C soluble antigens. Culture of CSF specimens was used as the standard and all laboratory procedures were performed blind. The mean CSF erythrocyte count was 66,406 cells/mm3 in the cases and 11,560 cells/mm3 in the controls. The sensitivity and the specificity of LPAT were 83.8 and 94.0%, respectively, suggesting that LPAT is a useful diagnostic tool even in blood stained CSF specimens. PMID:7876387

  19. Delayed presentation of traumatic cerebrospinal fluid rhinorrhea: Case report and literature review.

    PubMed

    Guyer, Richard A; Turner, Justin H

    2015-01-01

    Cerebrospinal fluid (CSF) leak is one of several complications that can occur after traumatic skull base injury. Although most patients present soon after the injury occurs, some can present years later, with resulting morbidity and the need for additional procedures. We present a case of a patient with a sphenoid sinus CSF leak who presented 12 years after a closed head injury that included a sphenoethmoid skull base fracture. We also reviewed the literature on this topic, with a discussion of previous reports of CSF leaks that occurred months, years, or decades after trauma. A late onset CSF leak appears to be a rare but important complication of traumatic skull base injury. This case highlights the need for clinicians to remain vigilant to the possibility of delayed CSF rhinorrhea, even years after traumatic head injury.

  20. Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

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

    PubMed Central

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

    1986-01-01

    Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis. PMID:3533984

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

    SciTech Connect

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

    1984-02-01

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

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

    PubMed

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

    1984-02-01

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

  4. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update.

    PubMed

    del Campo, Marta; Mollenhauer, Brit; Bertolotto, Antonio; Engelborghs, Sebastiaan; Hampel, Harald; Simonsen, Anja Hviid; Kapaki, Elisabeth; Kruse, Niels; Le Bastard, Nathalie; Lehmann, Sylvain; Molinuevo, Jose L; Parnetti, Lucilla; Perret-Liaudet, Armand; Sáez-Valero, Javier; Saka, Esen; Urbani, Andrea; Vanmechelen, Eugeen; Verbeek, Marcel; Visser, Pieter Jelle; Teunissen, Charlotte

    2012-08-01

    Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.

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

    PubMed

    Almeida, Sérgio Monteiro de

    2013-09-01

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

  6. Alzheimer’s Disease: Biomarkers in the Genome, Blood, and Cerebrospinal Fluid

    PubMed Central

    Huynh, Rose Ann; Mohan, Chandra

    2017-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that slowly destroys memory and thinking skills, resulting in behavioral changes. It is estimated that nearly 36 million are affected globally with numbers reaching 115 million by 2050. AD can only be definitively diagnosed at autopsy since its manifestations of senile plaques and neurofibrillary tangles throughout the brain cannot yet be fully captured with current imaging technologies. Current AD therapeutics have also been suboptimal. Besides identifying markers that distinguish AD from controls, there has been a recent drive to identify better biomarkers that can predict the rates of cognitive decline and neocortical amyloid burden in those who exhibit preclinical, prodromal, or clinical AD. This review covers biomarkers of three main types: genes, cerebrospinal fluid-derived, and blood-derived biomarkers. Looking ahead, cutting-edge OMICs technologies, including proteomics and metabolomics, ought to be fully tapped in order to mine even better biomarkers for AD that are more predictive. PMID:28373857

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

    PubMed

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

    2014-09-01

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

  8. Quantification of Amino Acid Neurotransmitters in Cerebrospinal Fluid of Patients with Neurocysticercosis

    PubMed Central

    Camargo, José Augusto; Bertolucci, Paulo Henrique Ferreira

    2015-01-01

    Background : Neurocysticercosis is a parasitic disease that affects the central nervous system. Its main clinical manifestations are epileptic seizures. The objective of this study was to investigate the correlation between neurotransmitter concentrations in cerebrospinal fluid (CSF) and the different evolutive forms of neurocysticercosis with or without seizures. Methods : Neurotransmitter concentrations (Aspartate, Glutamate, GABA, Glutamine, Glycine, Taurine) were determined in CSF samples from 42 patients with neurocysticercosis divided into patients with the active cystic form (n = 24, 12 with and 12 without seizures) and patients with calcified form (n = 18, 12 with and 6 without seizures), and a control group consisting of 59 healthy subjects. Results : Alterations in amino acid concentration were observed in all patients with neurocysticercosis. Conclusion : We conclude that disturbances in amino acid metabolism accompany the presentation of neurocysticercosis. Replacement of the terms inactive cyst by reactive inactive cyst and calcification by reactive calcification is suggested. PMID:26157521

  9. New insights into the glucose oxidase stick test for cerebrospinal fluid rhinorrhoea.

    PubMed

    Baker, E H; Wood, D M; Brennan, A L; Baines, D L; Philips, B J

    2005-08-01

    Rhinorrhoea is a clinical sign of cerebrospinal fluid (CSF) leakage in patients with skull fracture, but can also be attributable to respiratory secretions or tears. Laboratory tests confirming the presence of CSF are not sufficiently rapid to support clinical decision making in the emergency department and may not be universally available. Detection of glucose in nasal discharge was traditionally used to diagnose CSF leak at the bedside, but has fallen into disuse as it has poor positive predictive value. We propose an algorithm to improve the diagnostic value of this test taking into consideration factors we have found to affect the glucose concentration of respiratory secretions. In patients at risk of CSF leak, nasal discharge is likely to contain CSF if glucose is present in the absence of visible blood, if blood glucose is <6 mmol x L(-1), and if there are no symptoms of upper respiratory tract infection.

  10. Syndrome of Headache Accompanied with Transient Neurologic Deficits and Cerebrospinal Fluid Lymphocytosis

    PubMed Central

    ÇOBAN, Arzu; SHUGAIV, Erkingül; TÜZÜN, Erdem

    2013-01-01

    The syndrome of headache accompanied with transient neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL), is a rare, benign and self limiting syndrome. In the 2nd Edition of the International Classification of Headache Disorders, HaNDL syndrome was defined in secondary headache group as “Headache attributed to non-vascular intracranial disorder”. The etiology of HaNDL is still unknown. In recent years, some authors have shown that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis. In this paper, the definition of HaNDL syndrome, clinical picture and epidemiology of HaNDL syndrome, etiopathogenesis, differential diagnosis and treatment will be reviewed with the recent literature.

  11. Relation of cerebrospinal fluid/plasma HIV-RNA discordance with neurocognitive impairment.

    PubMed

    Cárdenas, Graciela; López-González, M; Monzón-Falconi, J F; Soto-Hernández, J L; Perales-Martínez, D; López-Vejar, C

    2015-01-01

    Neurological involvement is common in patients infected with HIV. The effectiveness of antiretroviral drugs in lowering the levels of HIV-RNA in cerebrospinal fluid (CSF) is limited by their inability to cross the blood-brain barrier. Discordance in CSF/plasma HIV-RNA levels may have a bearing on the progression of neurological disease in these patients. We report a woman with subacute neurocognitive impairment and abnormal findings on brain MRI, in whom there was a discordance between CSF/plasma HIV-RNA levels. The patient improved after a change in her highly active antiretroviral therapy (HAART) regimen. We also reviewed the available literature on the subject and found seven articles describing 27 patients.

  12. Transforming growth factor-β1 in the cerebrospinal fluid of patients with distinct neurodegenerative diseases.

    PubMed

    Masuda, Tomoyuki; Itoh, Junko; Koide, Takuya; Tomidokoro, Yasushi; Takei, Yosuke; Ishii, Kazuhiro; Tamaoka, Akira

    2017-01-01

    A chronic inflammatory condition may underlie neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). For example, both PD and AD patients show an increase in transforming growth factor-β1 (TGF-β1) levels in their cerebrospinal fluid (CSF). TGF-β1 is a cytokine that inhibits inflammation. In the present study, using an enzyme-linked immunosorbent assay, we tested the hypothesis that the level of TGF-β1 in the CSF of patients with amyotrophic lateral sclerosis (ALS), spinocerebellar degeneration (SCD), or multiple system atrophy-cerebellar subtype (MSA-C) would be elevated compared with that of normal controls. We found that TGF-β1 levels in the CSF were not significantly different between these patients and normal controls. Our data suggest that the level of TGF-β1 in the CSF is an unreliable biomarker of ALS, SCD, and MSA-C.

  13. Cerebrospinal fluid infection after lumbar nerve root steroid injection: a case report

    PubMed Central

    Kim, Seong-Su; Shim, Sung Min; Cho, Hae Jun

    2017-01-01

    A 45-year-old woman was admitted due to severe headache and neck stiffness. She had visited a local clinic for back pain and received a lumbar nerve root steroid injection 10 days before admission. Computed tomography and magnetic resonance imaging showed psoas abscess, pneumocephalus, and subdural hygroma. She was diagnosed with psoas abscess and meningitis. The abscess and external ventricle were drained, and antibiotics were administered. Unfortunately, the patient died on hospital day 19 due to diffuse leptomeningitis. Lumbar nerve root steroid injections are commonly used to control back pain. Vigilance to "red flag signs" and a rapid diagnosis can prevent lethal outcomes produced by rare and unexpected complications related to infection. Here, we report a case of fatal meningitis after infection of the cerebrospinal fluid following a lumbar nerve root steroid injection. PMID:28184274

  14. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature.

    PubMed

    Grimes, D T; Boswell, C W; Morante, N F C; Henkelman, R M; Burdine, R D; Ciruna, B

    2016-06-10

    Idiopathic scoliosis (IS) affects 3% of children worldwide, yet the mechanisms underlying this spinal deformity remain unknown. Here we show that ptk7 mutant zebrafish, a faithful developmental model of IS, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yields IS phenotypes. We define a finite developmental window for motile cilia in zebrafish spine morphogenesis. Notably, restoration of cilia motility after the onset of scoliosis blocks spinal curve progression. Together, our results indicate a critical role for cilia-driven CSF flow in spine development, implicate irregularities in CSF flow as an underlying biological cause of IS, and suggest that noninvasive therapeutic intervention may prevent severe scoliosis.

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

    PubMed

    Teunissen, Charlotte; Menge, Til; Altintas, Ayse; Álvarez-Cermeño, José C; Bertolotto, Antonio; Berven, Frode S; Brundin, Lou; Comabella, Manuel; Degn, Matilde; Deisenhammer, Florian; Fazekas, Franz; Franciotta, Diego; Frederiksen, Jette L; Galimberti, Daniela; Gnanapavan, Sharmilee; Hegen, Harald; Hemmer, Bernhard; Hintzen, Rogier; Hughes, Steve; Iacobaeus, Ellen; Kroksveen, Ann C; Kuhle, Jens; Richert, John; Tumani, Hayrettin; Villar, Luisa M; Drulovic, Jelena; Dujmovic, Irena; Khalil, Michael; Bartos, Ales

    2013-11-01

    The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.

  16. Lassa fever encephalopathy: Lassa virus in cerebrospinal fluid but not in serum.

    PubMed

    Günther, S; Weisner, B; Roth, A; Grewing, T; Asper, M; Drosten, C; Emmerich, P; Petersen, J; Wilczek, M; Schmitz, H

    2001-08-01

    The pathogenesis of neurologic complications of Lassa fever is poorly understood. A Nigerian patient had fever, disorientation, seizures, and blood-brain barrier dysfunction, and Lassa virus was found in cerebrospinal fluid (CSF) but not in serum. The concentration of Lassa virus RNA in CSF corresponded to 1 x 10(3) pfu/mL, as determined by a quantitative real-time polymerase chain reaction assay. To characterize the Lassa virus in CSF, the 3.5-kb S RNA was sequenced. In the S RNA coding sequences, the CSF strain differed between 20% and 24.6% from all known prototype strains. These data suggest that Lassa virus or specific Lassa virus strains can persist in the central nervous system and thus contribute to neuropathogenesis. Lassa virus infection should be considered in West African patients or in travelers returning from this area who present only with fever and neurologic signs.

  17. Effect of craniotomy and cerebrospinal fluid loss on the inner ear. An experimental study.

    PubMed

    Walsted, A; Garbarsch, C; Michaels, L

    1994-11-01

    Craniotomy with cerebrospinal fluid (CSF) suction was performed on 18 guinea pigs to determine the effects on the inner ear morphology. Six control animals received anaesthesia only and 12 were operated on with a postoperative survival time of 1 or 24 h. The histologic examinations showed no signs of endolymphatic hydrops or injury to other structures in any of the animals. In 11 of the operated animals, red blood corpuscles were demonstrated in the perilymphatic space of the cochlea, the subarachnoid space, and the cochlear aqueduct (CA). After 1 h survival time blood had entered primarily the basal part of the scala tympani, but in the animals of 24 h survival time the blood was more abundant in both the scala tympani and the scala vestibuli indicating flow within the inner ear. The CA thus provides a pathway between the CSF and the whole of the perilymph through which noxious effects could take place.

  18. [Cytology of the cerebrospinal fluid in dogs with brain tumors and spinal cord compression. Part 4].

    PubMed

    Grevel, V; Machus, B; Steeb, C

    1992-08-01

    The results of cerebrospinal fluid (CSF) cytology of 9 dogs with brain tumors and 50 dogs with spinal cord compression are discussed. Of the 50 dogs with spinal cord compression, disc protrusion was diagnosed in 31, myelomalacia in 7, discospondylitis in 3 and spinal cord tumors in 9 dogs. In 4 of 9 dogs with brain tumors, tumor cells could be found by the sedimentation apparatus of Kölmel. Pleocytosis existed in 6 patients. In about 70% (29 of 41) of cases with disc protrusion, more than 200 cells could be evaluated in the CSF sediment, consisting mostly of transformed lymphocytes and activated monocytes. As the neurologic deficits increased, the amount of cells and especially cell complexes increased. This was especially evident in cases with myelomalacia of the spinal cord. Only in cases with discospondylitis or spinal cord neoplasia was the CSF cytology unchanged.

  19. The Relief of Unilateral Painful Thoracic Radiculopathy without Headache from Remote Spontaneous Spinal Cerebrospinal Fluid Leak

    PubMed Central

    Son, Byung-chul; Ha, Sang-woo; Lee, Si-hoon; Choi, Jin-gyu

    2016-01-01

    Spontaneous intracranial hypotension (SIH) caused by spontaneous spinal cerebrospinal fluid (CSF) leaks produces orthostatic headaches. Although upper arm pain or paresthesia is reportedly associated with SIH from spontaneous spinal CSF leak in the presence of orthostatic headache, low thoracic radicular pain due to spontaneous spinal CSF leak unassociated with postural headache is extremely rare. We report a 67-year-old female who presented with chronic, positional radicular right T11 pain. Computed tomography myelography showed a spontaneous lumbar spinal CSF leak at L2-3 and repeated lumbar epidural blood patches significantly alleviated chronic, positional, and lower thoracic radiculopathic pain. The authors speculate that a chronic spontaneous spinal CSF leak not severe enough to cause typical orthostatic headache or epidural CSF collection may cause local symptoms such as irritation of a remote nerve root. There might be considerable variabilities in the clinical features of SIH which can present a diagnostic challenge. PMID:27445613

  20. Incidence of cerebrospinal fluid leak following petrosectomy and analysis of avoidance techniques.

    PubMed

    Walcott, Brian P; Nahed, Brian V; Sarpong, Yaw; Kahle, Kristopher T; Sekhar, Laligam N; Ferreira, Manuel J

    2012-01-01

    A cerebrospinal fluid (CSF) leak following skull base surgery can lead to meningitis, impaired wound healing, and often requires re-operation and/or CSF diversion. Thirty-two patients underwent a presigmoid, transpetrosal approach to skull base aneurysms and tumors. A vascularized temporalis muscle flap was utilized during the closure of the initial skull base reconstruction in 18 of the 32 patients. A temporary CSF diversion was utilized in 23 of the 32 patients. A permanent shunt was placed in eight patients. One patient developed a postoperative CSF leak from the contralateral ear due to a congenital abnormality in the middle ear. Another patient, who did not have a vascularized temporalis muscle flap reconstruction, developed a postoperative CSF leak in the context of an operation for recurrent tumor and prior radiation treatment. CSF diversion and vascularized temporalis muscle flaps are effective in preventing the development of postoperative CSF leaks following petrosectomy.

  1. [Viridans streptococci isolated from cerebrospinal fluid. Clinical significance of 9 cases].

    PubMed

    Alba, D; Guerra, A; Peña, P; Molina, F

    1997-02-01

    Viridans streptococci (VS) are often isolated from cerebrospinal fluid (CSF). However, the significance of such isolates is poorly understood. In the present study we carry out a retrospective analysis of 9 patients in whom VS were isolated from CSF during a 1-year period at La Paz Hospital. Two patients (22.2%) had meningitis diagnosed through clinical, laboratory and bacteriologic findings. Both patients had predisposition diseases (previous difficult spinal tap, ventriculo-peritoneal shunt). The other isolations were considered as contaminants. Three patients (33.3%) with no VS meningitis had other different serious disease (sepsis without bacteriologic confirmation). VS are isolated with relative frequency from CSF, although they cause meningitis in less than one-quarter of the cases (those who have a predisposition disease). In the other cases, VS are isolated as contaminants of CSF and other disease should be search as cause of patient symptoms.

  2. Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  3. Report of Two Cases of Aseptic Meningitis with Persistence of Pneumococcal Cell Wall Components in Cerebrospinal Fluid after Pneumococcal Meningitis▿

    PubMed Central

    Angoulvant, François; Lachenaud, Julie; Mariani-Kurkdjian, Patricia; Aubertin, Guillaume; Houdouin, Véronique; Lorrot, Mathie; de Los Angeles, Laure; Bingen, Edouard; Bourrillon, Antoine; Faye, Albert

    2006-01-01

    We describe two cases of aseptic meningitis occurring some time after pneumococcal meningitis. Both cases may have resulted from an inflammatory response to persistent pneumococcal cell membrane components, as the cerebrospinal fluid samples were positive by the Binax NOW Streptococcus pneumoniae antigen test. Potential mechanisms and diagnostic impact are discussed. PMID:17005744

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

    PubMed

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

    2015-08-28

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2014-01-01

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

  7. Subpeak regional analysis of intracranial pressure waveform morphology based on cerebrospinal fluid hydrodynamics in the cerebral aqueduct and prepontine cistern.

    PubMed

    Hamilton, Robert B; Baldwin, Kevin; Vespa, Paul; Bergsneider, Marvin; Hu, Xiao

    2012-01-01

    The objective of this study is to investigate the relationship between intracranial pressure (ICP) pulse waveform morphology and selected hydrodynamic metrics of cerebrospinal fluid (CSF) movement using a novel method for ICP pulse pressure regional analysis based on the Morphological Clustering and Analysis of Continuous Intracranial Pulse (MOCAIP) algorithm.

  8. Relationship between intracranial granulomas and cerebrospinal fluid levels of gamma interferon and interleukin-10 in patients with tuberculous meningitis.

    PubMed

    Mansour, Adel M; Frenck, Robert W; Darville, Toni; Nakhla, Isabelle A; Wierzba, Thomas F; Sultan, Yehia; Bassiouny, Magdy I; McCarthy, Kathryn; Jacobs, Richard F

    2005-02-01

    Cerebrospinal fluid gamma interferon (IFN-gamma) and interleukin-10 levels in 39 patients with tuberculous meningitis were serially measured. Cytokine levels did not predict intracranial granuloma (IG) development, but IFN-gamma levels in the top quartile after 1 month of therapy were highly associated (odds ratio = 18) with detection of an IG by computed tomography scanning.

  9. Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

    PubMed Central

    Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

    2015-01-01

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

  10. Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

    PubMed Central

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C.; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2015-01-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of −0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, −0.12 (P = 0.037); delayed recall, −0.05 (P = 0.002); New Dot Test, −0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  11. Cerebrospinal Fluid Biomarker Signature in Alzheimer’s Disease Neuroimaging Initiative Subjects

    PubMed Central

    Shaw, Leslie M.; Vanderstichele, Hugo; Knapik-Czajka, Malgorzata; Clark, Christopher M.; Aisen, Paul S.; Petersen, Ronald C.; Blennow, Kaj; Soares, Holly; Simon, Adam; Lewczuk, Piotr; Dean, Robert; Siemers, Eric; Potter, William; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2009-01-01

    Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer’s disease (AD) in Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid-β 1 to 42 peptide (Aβ1-42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and Aβ1-42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. Results CSF Aβ1-42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1-42, t-tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/Aβ1-42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation The CSF biomarker signature of AD defined by Aβ1-42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. PMID:19296504

  12. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study

    PubMed Central

    Leuzy, Antoine; Chiotis, Konstantinos; Hasselbalch, Steen G.; Rinne, Juha O.; de Mendonça, Alexandre; Otto, Markus; Lleó, Alberto; Castelo-Branco, Miguel; Santana, Isabel; Johansson, Jarkko; Anderl-Straub, Sarah; von Arnim, Christine A. F.; Beer, Ambros; Blesa, Rafael; Fortea, Juan; Herukka, Sanna-Kaisa; Portelius, Erik; Pannee, Josef; Zetterberg, Henrik; Blennow, Kaj

    2016-01-01

    The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40. Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer’s and Parkinson’s Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer’s disease, while more variable results were observed for cognitively normal and non-Alzheimer’s disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry

  13. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study.

    PubMed

    Leuzy, Antoine; Chiotis, Konstantinos; Hasselbalch, Steen G; Rinne, Juha O; de Mendonça, Alexandre; Otto, Markus; Lleó, Alberto; Castelo-Branco, Miguel; Santana, Isabel; Johansson, Jarkko; Anderl-Straub, Sarah; von Arnim, Christine A F; Beer, Ambros; Blesa, Rafael; Fortea, Juan; Herukka, Sanna-Kaisa; Portelius, Erik; Pannee, Josef; Zetterberg, Henrik; Blennow, Kaj; Nordberg, Agneta

    2016-09-01

    The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40 Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer's and Parkinson's Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference

  14. Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions.

    PubMed

    Ueno, Masaki; Chiba, Yoichi; Murakami, Ryuta; Matsumoto, Koichi; Kawauchi, Machi; Fujihara, Ryuji

    2016-04-01

    Blood-borne substances can invade into the extracellular spaces of the brain via endothelial cells in sites without the blood-brain barrier (BBB), and can travel through the interstitial fluid (ISF) of the brain parenchyma adjacent to non-BBB sites. It has been shown that cerebrospinal fluid (CSF) drains directly into the blood via the arachnoid villi and also into lymph nodes via the subarachnoid spaces of the brain, while ISF drains into the cervical lymph nodes through perivascular drainage pathways. In addition, the glymphatic pathway of fluids, characterized by para-arterial pathways, aquaporin4-dependent passage through astroglial cytoplasm, interstitial spaces, and paravenous routes, has been established. Meningeal lymphatic vessels along the superior sagittal sinus were very recently discovered. It is known that, in mice, blood-borne substances can be transferred to areas with intact BBB function, such as the medial regions of the hippocampus, presumably through leaky vessels in non-BBB sites. In the present paper, we review the clearance mechanisms of interstitial substances, such as amyloid-β peptides, as well as summarize models of BBB deterioration in response to different types of insults, including acute ischemia followed by reperfusion, hypertension, and chronic hypoperfusion. Lastly, we discuss the relationship between perivascular clearance and brain disorders.

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

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

    PubMed Central

    Koczula, Anna; Jarek, Michael; Visscher, Christian; Valentin-Weigand, Peter; Goethe, Ralph; Willenborg, Jörg

    2017-01-01

    Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF) revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq). In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism). In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments. PMID:28212285

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

    PubMed

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

    2014-05-06

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

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

    PubMed

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

    2014-01-01

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

  19. Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease

    PubMed Central

    Simon, Matthew J.; Iliff, Jeffrey J.

    2015-01-01

    Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer’s disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the ‘glymphatic’ system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. PMID:26499397

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  1. Sex-Related Differences in Rat Choroid Plexus and Cerebrospinal Fluid: A cDNA Microarray and Proteomic Analysis.

    PubMed

    Quintela, T; Marcelino, H; Deery, M J; Feret, R; Howard, J; Lilley, K S; Albuquerque, T; Gonçalves, I; Duarte, A C; Santos, C R A

    2016-01-01

    The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood and the cerebrospinal fluid (CSF), which is mostly produced by the CP itself. Because the CP transcriptome is regulated by the sex hormone background, the present study compared gene/protein expression profiles in the CP and CSF from male and female rats aiming to better understand sex-related differences in CP functions and brain physiology. We used data previously obtained by cDNA microarrays to compare the CP transcriptome between male and female rats, and complemented these data with the proteomic analysis of the CSF of castrated and sham-operated males and females. Microarray analysis showed that 17 128 and 17 002 genes are expressed in the male and female CP, which allowed the functional annotation of 141 and 134 pathways, respectively. Among the most expressed genes, canonical pathways associated with mitochondrial dysfunctions and oxidative phosphorylation were the most prominent, whereas the most relevant molecular and cellular functions annotated were protein synthesis, cellular growth and proliferation, cell death and survival, molecular transport, and protein trafficking. No significant differences were found between males and females regarding these pathways. Seminal functions of the CP differentially regulated between sexes were circadian rhythm signalling, as well as several canonical pathways related to stem cell differentiation, metabolism and the barrier function of the CP. The proteomic analysis identified five down-regulated proteins in the CSF samples from male rats compared to females and seven proteins exhibiting marked variation in the CSF of gonadectomised males compared to sham animals, whereas no differences were found between sham and ovariectomised females. These data clearly show sex-related differences in CP gene expression and CSF protein composition that may impact upon neurological diseases.

  2. Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

    PubMed Central

    Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

    2014-01-01

    The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD. PMID:25426023

  3. Cognitive Performance and Cerebrospinal Fluid Biomarkers of Neurodegeneration: A Study of Patients with Bipolar Disorder and Healthy Controls

    PubMed Central

    Rolstad, Sindre; Jakobsson, Joel; Sellgren, Carl; Ekman, Carl-Johan; Blennow, Kaj; Zetterberg, Henrik; Pålsson, Erik; Landén, Mikael

    2015-01-01

    The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (Aβ)1-42, ratios of Aβ42/40 and Aβ42/38, soluble amyloid precursor protein α and β, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers. In patients, the CSF biomarkers explained a significant proportion of the variance (15–36%, p=.002 - <.0005) in all cognitive domains independently of age, medication, disease status, and bipolar subtype I or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain changes, i.e., P-tau and Aβ1-42, did not contribute significantly. In healthy controls, CSF biomarkers did not explain the variance in cognitive performance. Selected CSF biomarkers of neurodegenerative processes accounted for cognitive performance in persons with bipolar disorder, but not for healthy controls. Specifically, the ratios of Aβ42/40 and Aβ42/38 were consistently associated with altered cognitive performance. PMID:25954806

  4. Alzheimer's disease: Elevated pigment epithelium-derived factor in the cerebrospinal fluid is mostly of systemic origin.

    PubMed

    Lang, Veronika; Zille, Marietta; Infante-Duarte, Carmen; Jarius, Sven; Jahn, Holger; Paul, Friedemann; Ruprecht, Klemens; Pina, Ana Luisa

    2017-04-15

    Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19). We established CSF/serum quotient diagrams to determine the fraction of intrathecally synthesized PEDF in CSF. We found that PEDF is significantly increased in CSF of patients with AD, FTD, and bacterial meningitis. Remarkably, PEDF concentrations were also significantly elevated in serum of patients with AD. CSF/serum quotient diagrams demonstrated that elevated PEDF concentrations in CSF of patients with AD are mostly due to elevated PEDF concentrations in serum. These findings underscore the importance of relating concentrations of proteins in CSF to their respective concentrations in serum to avoid erroneous interpretations of increased protein concentrations in lumbar CSF.

  5. Interaction between SCO-spondin and low density lipoproteins from embryonic cerebrospinal fluid modulates their roles in early neurogenesis

    PubMed Central

    Vera, América; Recabal, Antonia; Saldivia, Natalia; Stanic, Karen; Torrejón, Marcela; Montecinos, Hernán; Caprile, Teresa

    2015-01-01

    During early stages of development, encephalic vesicles are composed by a layer of neuroepithelial cells surrounding a central cavity filled with embryonic cerebrospinal fluid (eCSF). This fluid contains several morphogens that regulate proliferation and differentiation of neuroepithelial cells. One of these neurogenic factors is SCO-spondin, a giant protein secreted to the eCSF from early stages of development. Inhibition of this protein in vivo or in vitro drastically decreases the neurodifferentiation process. Other important neurogenic factors of the eCSF are low density lipoproteins (LDL), the depletion of which generates a 60% decrease in mesencephalic explant neurodifferentiation. The presence of several LDL receptor class A (LDLrA) domains (responsible for LDL binding in other proteins) in the SCO-spondin sequence suggests a possible interaction between both molecules. This possibility was analyzed using three different experimental approaches: (1) Bioinformatics analyses of the SCO-spondin region, that contains eight LDLrA domains in tandem, and of comparisons with the LDL receptor consensus sequence; (2) Analysis of the physical interactions of both molecules through immunohistochemical colocalization in embryonic chick brains and through the immunoprecipitation of LDL with anti-SCO-spondin antibodies; and (3) Analysis of functional interactions during the neurodifferentiation process when these molecules were added to a culture medium of mesencephalic explants. The results revealed that LDL and SCO-spondin interact to form a complex that diminishes the neurogenic capacities that both molecules have separately. Our work suggests that the eCSF is an active signaling center with a complex regulation system that allows for correct brain development. PMID:26074785

  6. Changes with age in leucocyte counts, protein and IgG content of lumbar cerebrospinal fluid (CSF) of patients with inflammatory, ischemic, and hemorrhagic diseases or tumors of the central nervous system (CNS).

    PubMed

    Kleine, T O; Weber, L; Zöfel, P

    1988-01-01

    Parameters of blood-brain barrier (BBB) function and of humoral and cellular immune response were determined in lumbar CSF and blood serum samples from 717 patients and statistically compared to "healthy" controls (n = 190). Leucocyte counts (mainly mononuclear cells), total protein and IgG levels in CSF were significantly higher, and prealbumin fraction mostly lower in patients, besides other alterations of protein electrophoresis. Serum fractions (median) of protein electrophoresis were within the reference range. When parameters were correlated with age, a significant increase of total protein of 1.62 mg/dl and of IgG of 0.13 mg/dl per 10 years of age was found in lumbar CSF of controls. Elevated leucocyte counts did not correlate with age of patients, but they increased significantly with age, with respect to controls, to a higher extent in patients with polyneuritis, ischemia and injury; they decreased in patients with brain tumors and polyneuropathy. When compared to controls, elevated total protein levels significantly increased with age only with tumors and injury patients. In multiple sclerosis, IgG increased and beta-globulin fraction decreased significantly in CSF with age. The findings point to age-dependent alterations of BBB and immune response only in some patients groups which were different from those of controls.

  7. Understanding How the Subcommissural Organ and Other Periventricular Secretory Structures Contribute via the Cerebrospinal Fluid to Neurogenesis.

    PubMed

    Guerra, Maria M; González, César; Caprile, Teresa; Jara, Maryoris; Vío, Karin; Muñoz, Rosa I; Rodríguez, Sara; Rodríguez, Esteban M

    2015-01-01

    The dynamic and molecular composition of the cerebrospinal fluid (CSF) and, consequently, the CSF physiology is much more complex and fascinating than the simplistic view held for decades. Signal molecules either transported from blood to CSF or secreted into the CSF by circumventricular organs and CSF-contacting neurons, use the CSF to reach their targets in the brain, including the pre- and postnatal neurogenic niche. The subcommissural organ (SCO), a highly conserved brain gland present throughout the vertebrate phylum, is one of the sources for signals, as well as the choroid plexus, tanycytes and CSF-contacting neurons. The SCO secretes into the fetal and adult CSF SCO-spondin, transthyretin, and basic fibroblast growth factor. These proteins participate in certain aspects of neurogenesis, such as cell cycle of neural stem cells, neuronal differentiation, and axon pathfinding. Through the CSF, the SCO-secretory proteins may reach virtually any target in the embryonic and adult central nervous system. Since the SCO continues to secrete throughout life span, it seems likely that the neurogenetic property of the SCO compounds would be targeted to the niches where neurogenesis continues in adulthood. This review is aimed to bring into discussion early and new evidence concerning the role(s) of the SCO, and the probable mechanisms by which SCO compounds can readily reach the neurogenic niche of the subventricular zone flowing with the CSF to participate in the regulation of the neurogenic niche. As we unfold the multiples trans-fluid talks between discrete brain domains we will have more tools to influence such talks.

  8. Understanding How the Subcommissural Organ and Other Periventricular Secretory Structures Contribute via the Cerebrospinal Fluid to Neurogenesis

    PubMed Central

    Guerra, Maria M.; González, César; Caprile, Teresa; Jara, Maryoris; Vío, Karin; Muñoz, Rosa I.; Rodríguez, Sara; Rodríguez, Esteban M.

    2015-01-01

    The dynamic and molecular composition of the cerebrospinal fluid (CSF) and, consequently, the CSF physiology is much more complex and fascinating than the simplistic view held for decades. Signal molecules either transported from blood to CSF or secreted into the CSF by circumventricular organs and CSF-contacting neurons, use the CSF to reach their targets in the brain, including the pre- and postnatal neurogenic niche. The subcommissural organ (SCO), a highly conserved brain gland present throughout the vertebrate phylum, is one of the sources for signals, as well as the choroid plexus, tanycytes and CSF-contacting neurons. The SCO secretes into the fetal and adult CSF SCO-spondin, transthyretin, and basic fibroblast growth factor. These proteins participate in certain aspects of neurogenesis, such as cell cycle of neural stem cells, neuronal differentiation, and axon pathfinding. Through the CSF, the SCO-secretory proteins may reach virtually any target in the embryonic and adult central nervous system. Since the SCO continues to secrete throughout life span, it seems likely that the neurogenetic property of the SCO compounds would be targeted to the niches where neurogenesis continues in adulthood. This review is aimed to bring into discussion early and new evidence concerning the role(s) of the SCO, and the probable mechanisms by which SCO compounds can readily reach the neurogenic niche of the subventricular zone flowing with the CSF to participate in the regulation of the neurogenic niche. As we unfold the multiples trans-fluid talks between discrete brain domains we will have more tools to influence such talks. PMID:26778959

  9. Increased sensitivity of bacterial detection in cerebrospinal fluid by fluorescent staining on low-fluorescence membrane filters.

    PubMed

    Durtschi, Jacob D; Erali, Maria; Bromley, L Kathryn; Herrmann, Mark G; Petti, Cathy A; Smith, Roger E; Voelkerding, Karl V

    2005-09-01

    A membrane-filter-based, fluorescent Gram stain method for bacterial detection in cerebrospinal fluid samples was developed and evaluated as a rapid, sensitive alternative to standard Gram stain protocols. A recently developed, modified version of the aluminium oxide membrane Anopore with low-fluorescence optical properties showed superior performance in this application. Other aspects of the fluorescent Gram stain system that were evaluated include membrane filter selection, strategies to reduce fluorescence fading and the effect of patient blood cells on bacterial detection in the fluorescently stained cerebrospinal fluid samples. The combination of the membrane filter's bacteria-concentrating ability and absolute retention along with high-contrast, fluorescent Gram discriminating dyes enabled rapid bacterial detection and Gram discrimination, with a 1-1.5 order of magnitude increase in the bacterial concentration limit of detection.

  10. Multiple sclerosis: Brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood

    PubMed Central

    Skulina, Christian; Schmidt, Stephan; Dornmair, Klaus; Babbe, Holger; Roers, Axel; Rajewsky, Klaus; Wekerle, Hartmut; Hohlfeld, Reinhard; Goebels, Norbert

    2004-01-01

    We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to clarify their unusual clinical presentation but were subsequently confirmed to have typical multiple sclerosis. One of the brain biopsy specimens had been previously investigated by microdissection and single-cell PCR to determine the clonal composition of brain-infiltrating T cells at the single-cell level. Using complementarity-determining region 3 spectratyping, we identified several identical, expanded CD8+ (but not CD4+) T cell clones in all three compartments. Some of the expanded CD8+ T cells also occurred in sorted CD38+ blood cells, suggesting that they were activated. Strikingly, some of the brain-infiltrating CD8+ T cell clones persisted for >5 years in the cerebrospinal fluid and/or blood and may thus contribute to the progression of the disease. PMID:14983026

  11. Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt-Jakob Disease in Slovak Patients: over 10-Year Period Review.

    PubMed

    Koscova, Silvia; Zakova Slivarichova, Dana; Tomeckova, Ivana; Melicherova, Katarina; Stelzer, Martin; Janakova, Alzbeta; Kosorinova, Dana; Belay, Girma; Mitrova, Eva

    2016-09-24

    Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Aβ 1-42 levels neither between both CJD forms nor between CJD patients and control group.

  12. The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    De Vos, Ann; Struyfs, Hanne; Jacobs, Dirk; Fransen, Erik; Klewansky, Tom; De Roeck, Ellen; Robberecht, Caroline; Van Broeckhoven, Christine; Duyckaerts, Charles; Engelborghs, Sebastiaan; Vanmechelen, Eugeen

    2016-01-01

    Background: In diagnosing Alzheimer’s disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Aβ1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers. Objective: We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Aβ1-42, Aβ1-40, and Aβ1-38. All six analytes were considered as single parameters as well as ratios. Methods: Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychologically (MMSE) examinations for at least one year. Results: The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio. Conclusion: This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline. PMID:27392859

  13. Genomic Comparison of Escherichia coli K1 Strains Isolated from the Cerebrospinal Fluid of Patients with Meningitis †

    PubMed Central

    Yao, Yufeng; Xie, Yi; Kim, Kwang Sik

    2006-01-01

    Escherichia coli is a major cause of enteric/diarrheal diseases, urinary tract infections, and sepsis. E. coli K1 is the leading gram-negative organism causing neonatal meningitis, but the microbial basis of E. coli K1 meningitis is incompletely understood. Here we employed comparative genomic hybridization to investigate 11 strains of E. coli K1 isolated from the cerebrospinal fluid (CSF) of patients with meningitis. These 11 strains cover the majority of common O serotypes in E. coli K1 isolates from CSF. Our data demonstrated that these 11 strains of E. coli K1 can be categorized into two groups based on their profile for putative virulence factors, lipoproteins, proteases, and outer membrane proteins. Of interest, we showed that some open reading frames (ORFs) encoding the type III secretion system apparatus were found in group 2 strains but not in group 1 strains, while ORFs encoding the general secretory pathway are predominant in group 1 strains. These findings suggest that E. coli K1 strains isolated from CSF can be divided into two groups and these two groups of E. coli K1 may utilize different mechanisms to induce meningitis. PMID:16552050

  14. Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease

    PubMed Central

    Öhrfelt, Annika; Johansson, Per; Wallin, Anders; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj; Svensson, Johan

    2016-01-01

    Background Dysfunctions of the ubiquitin proteasome system (UPS), including the highly abundant neuronal enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and autophagy-related changes (lysosomal degradation) are implicated in several neurodegenerative disorders including Alzheimer's disease (AD). Method This study evaluated cerebrospinal fluid (CSF) levels of UCH-L1, protein deglycase (DJ-1), neuron-specific enolase (NSE), and tau phosphorylated at threonine 231 (P-tau231) in two independent patient and control cohorts. Cohort 1 included CSF samples from subjects having an AD biomarker profile (n = 10) or a control biomarker profile (n = 31), while cohort 2 was a monocenter clinical study including patients with AD (n = 32), mild cognitive impairment (n = 13), other dementias (n = 15), as well as cognitively healthy controls (n = 20). Results UCH-L1 and P-tau231 were elevated in AD patients compared to controls in both cohorts. CSF levels of DJ-1 and NSE were unchanged in the AD group, whereas they were decreased in the group of other dementia compared to controls in the clinical study. Conclusion Our main findings support that the UPS pathway may be impaired in AD, and UCH-L1 may serve as an additional CSF biomarker for AD. PMID:27504117

  15. Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS.

    PubMed

    Blanco, M E; Encinas, E; González, O; Rico, E; Vozmediano, V; Suárez, E; Alonso, R M

    2015-09-01

    In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h).

  16. High signal in cerebrospinal fluid mimicking subarachnoid haemorrhage on FLAIR following acute stroke and intravenous contrast medium.

    PubMed

    Dechambre, S D; Duprez, T; Grandin, C B; Lecouvet, F E; Peeters, A; Cosnard, G

    2000-08-01

    We describe five cases of high signal in the cerebrospinal fluid (CSF) on fast-FLAIR images 24-48 h after onset of stroke. All the patients had undergone perfusion-weighted MRI within 6 h of the onset of the symptoms. The CSF was far brighter than the cortical gyri. The high signal was diffusely around both cerebral hemispheres in two cases and around one hemisphere in two others; it was focal, around the acute ischaemic lesion, in one. CT was normal in all cases. The CSF high signal was transient, decreasing in extent and intensity with time and resolving completely within 3-6 days. It was not associated with worsening of the clinical state or poor outcome. Our explanation of this phenomena is hypothetical: we speculate that it could be due to disruption of the blood-brain barrier resulting in leakage of protein, gadolinium chelates, or both in to the subarachnoid space. It should not be confused with subarachnoid haemorrhage.

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

    NASA Astrophysics Data System (ADS)

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

    1987-12-01

    The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

  18. Opsoclonus-myoclonus-dysequilibrium syndrome: cytological and immunological dynamics in the serial cerebrospinal fluid in two patients.

    PubMed

    Bartos, Ales; Pitha, Jirí

    2003-12-01

    A peculiar clinical presentation characterized by the triad of opsoclonus,myoclonus and ataxia, mainly in a form of dysequilibrium, is usually associated with infectious or paraneoplastic processes. Serial cerebrospinal fluid (CSF) analysis in two patients with opsoclonus-myoclonus-dysequilibrium syndrome suggestive of viral encephalitis were performed from disease onset for up to 8 months. A cell count, cytology, total protein and glucose concentrations in CSF, the blood-CSF barrier function, intrathecal synthesis of immunoglobulins (Ig) in class M, G and A expressed as IgM, IgG and IgA indices and oligoclonal IgG bands were monitored. Cellular and humoral alterations in both patients were slight at the onset becoming more pronounced a month later. The kinetics of the CSF changes mirrored the subacute clinical deterioration and subsequent recovery. The delayed response in the CSF measures and the gradual clinical deterioration suggest the development of subacute brain inflammation. A mononuclear pleocytosis, including macrophages and plasma cells, increased within the first month and then normalized during the following weeks. Intrathecally synthesized IgM occurred only transiently after one month of illness, whereas intrathecal IgG production increased during the first month and persisted for at least eight months. An increasing number of oligoclonal IgG bands during the course, indicative of expanding local intrathecal synthesis, was noted. The dynamics of these CSF changes supports the hypothesis that opsoclonus-myoclonus syndrome is a post-infectious immune- mediated condition.

  19. Pneumocephalus leading to the diagnosis of cerebrospinal fluid leak and esophageal perforation after cervical spine surgery.

    PubMed

    Goodwin, C Rory; Boone, Christine E; Pendleton, James; Elder, Benjamin D; Wei, Zhikui; Hsu, Wesley; Sciubba, Daniel M; Witham, Timothy F

    2016-04-01

    Pneumocephalus is a collection of air within in the intracranial cavity, most commonly seen following traumatic injury or cranial surgeries. Esophageal injury and cerebrospinal fluid (CSF) leak are rare complications that may occur following anterior cervical discectomy and fusion (ACDF). We present a novel case of pneumocephalus arising from unrestricted leakage of CSF via coincident esophageal injury and durotomy in a patient who underwent an ACDF after trauma. A 21-year-old man presented to an outside hospital with C5/C6 subluxation, complete spinal cord injury, and quadriplegia from a motor vehicle accident. He underwent an ACDF, during which a CSF leak was observed. He was then transferred to our institution for rehabilitation and tracheostomy placement 1 week after the ACDF surgery. Following the tracheostomy, the patient developed intractable fevers and nonspecific symptoms. A CT scan demonstrated frontal pneumocephalus without mass effect. Air was found in the retropharyngeal space. There were no accumulations of CSF in the neck. Extravasation of contrast around instrumentation at C5/C6 on a cine esophagogram demonstrated an esophageal perforation at that level. Pneumocephalus may form when large volumes of CSF escape from the intracranial space and air is drawn into the space by the negative pressure. In this unusual case, the esophageal perforation promoted the formation of the pneumocephalus. Treatment included closure of both defects, disrupting the suspected communication between the intracranial space and the esophagus.

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

    PubMed Central

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

    2015-01-01

    The aim of the present report was to present the patient with an anterior cranial base fracture who developed post-traumatic cerebrospinal fluid rhinorrhea, which recovered after onset of meningitis complication. A 26-year-old male patient who had a traffic accident one week ago was sent to our clinic because of his rhinorrhea persisting for 4 days. On cranial computed tomography, fracture of the left frontal skull base and sinus walls, a fracture line on temporal bone, parenchymal bleeding in the vicinity of the frontal sinus, subarachnoidal bleeding and left temporal extradural hematoma were detected. Then he underwent sinus wall repair and extradural hematoma was drained through bifrontal craniotomy. However, rhinorrhea persisted which resulted a deterioration in consciousness and he entered into a deep somnolent state. When his symptoms of meningitis became apparent, rhinorrhea of the patient disappeared. The patient transferred in intensive care unit and re-connected to a lumbar drainage system. On cerebral magnetic resonance imaging, regression of contrast-enhanced lesions localized in the left anterotemporal and frontal and in the regions lateral to the right trigon and medial to the right thalamus and in the right posteroparietal regions was observed. Despite repair of the anterior cranial fracture and lumbar drainage, rhinorrhea may persist. Herein, development of meningitis caused disappearing of rhinorrhea symptoms without any need for surgical intervention. PMID:26309437

  1. Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis.

    PubMed

    van Dongen, Robin M; Zielman, Ronald; Noga, Marek; Dekkers, Olaf M; Hankemeier, Thomas; van den Maagdenberg, Arn Mjm; Terwindt, Gisela M; Ferrari, Michel D

    2017-01-01

    Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

  2. The circulation of the cerebrospinal fluid (CSF) in the spinal canal

    NASA Astrophysics Data System (ADS)

    Sanchez, Antonio L.; Martinez-Bazan, Carlos; Lasheras, Juan C.

    2016-11-01

    Cerebrospinal Fluid (CSF) is secreted in the choroid plexus in the lateral sinuses of the brain and fills the subarachnoid space bathing the external surfaces of the brain and the spinal canal. Absence of CSF circulation has been shown to impede its physiological function that includes, among others, supplying nutrients to neuronal and glial cells and removing the waste products of cellular metabolism. Radionuclide scanning images published by Di Chiro in 1964 showed upward migration of particle tracers from the lumbar region of the spinal canal, thereby suggesting the presence of an active bulk circulation responsible for bringing fresh CSF into the spinal canal and returning a portion of it to the cranial vault. However, the existence of this slow moving bulk circulation in the spinal canal has been a subject of dispute for the last 50 years. To date, there has been no physical explanation for the mechanism responsible for the establishment of such a bulk motion. We present a perturbation analysis of the flow in an idealized model of the spinal canal and show how steady streaming could be responsible for the establishment of such a circulation. The results of this analysis are compared to flow measurements conducted on in-vitro models of the spinal canal of adult humans.

  3. Cilia induced cerebrospinal fluid flow in the third ventricle of brain

    NASA Astrophysics Data System (ADS)

    Wang, Yong; Westendorf, Christian; Faubel, Regina; Eichele, Gregor; Bodenschatz, Eberhard

    2016-11-01

    Cerebrospinal fluid (CSF) conveys many physiologically important signaling factors through the ventricles of the mammalian brain. The walls of the ventricles are covered with motile cilia that were thought to generate a laminar flow purely following the curvature of walls. However, we recently discovered that cilia of the ventral third ventricle (v3V) generate a complex flow network along the wall, leading to subdivision of the v3V. The contribution of such cilia induced flow to the overall three dimensional volume flow remains to be investigated by using numerical simulation, arguably the best approach for such investigations. The lattice Boltzmann method is used to study the CFS flow in a reconstructed geometry of the v3V. Simulation of CSF flow neglecting cilia in this geometry confirmed that the previous idea about pure confined flow does not reflect the reality observed in experiment. The experimentally recorded ciliary flow network along the wall was refined with the smoothed particle hydrodynamics and then adapted as boundary condition in simulation. We study the contribution of the ciliary network to overall CSF flow and identify site-specific delivery of CSF constituents with respect to the temporal changes.

  4. Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease.

    PubMed

    Babić, Mirjana; Svob Štrac, Dubravka; Mück-Šeler, Dorotea; Pivac, Nela; Stanić, Gabrijela; Hof, Patrick R; Simić, Goran

    2014-08-28

    Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid β1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed.

  5. Simultaneous Detection of Five Pathogens from Cerebrospinal Fluid Specimens Using Luminex Technology

    PubMed Central

    Zhou, Linfu; Wu, Rui; Shi, Xiaodan; Feng, Dongyun; Feng, Guodong; Yang, Yining; Dai, Wen; Bian, Ting; Liu, Tingting; He, Ying; Shi, Ming; Zhao, Gang

    2016-01-01

    Early diagnosis and treatment are crucial for the outcome of central nervous system (CNS) infections. In this study, we developed a multiplex PCR-Luminex assay for the simultaneous detection of five major pathogens, including Mycobacterium tuberculosis, Cryptococcus neoformans, Streptococcus pneumoniae, and herpes simplex virus types 1 and 2, which frequently cause CNS infections. Through the hybridization reaction between multiplex PCR-amplified targets and oligonucleotide “anti-TAG” sequences, we found that the PCR-Luminex assay could detect as low as 101–102 copies of synthetic pathogen DNAs. Furthermore, 163 cerebrospinal fluid (CSF) specimens from patients with suspected CNS infections were used to evaluate the efficiency of this multiplex PCR-Luminex method. Compared with Ziehl-Neelsen stain, this assay showed a high diagnostic accuracy for tuberculosis meningitis (sensitivity, 90.7% and specificity, 99.1%). For cryptococcal meningitis, the sensitivity and specificity were 92% and 97.1%, respectively, compared with the May Grunwald Giemsa (MGG) stain. For herpes simplex virus types 1 and 2 encephalitis, the sensitivities were 80.8% and 100%, and the specificities were 94.2% and 99%, respectively, compared with Enzyme Linked Immunosorbent Assay (ELISA) assays. Taken together, this multiplex PCR-Luminex assay showed potential efficiency for the simultaneous detection of five pathogens and may be a promising supplement to conventional methods for diagnosing CNS infections. PMID:26861363

  6. MR measurement of cerebrospinal fluid velocity wave speed in the spinal canal.

    PubMed

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

    2009-06-01

    Noninvasive measurement of the speed with which the cerebrospinal fluid (CSF) velocity wave travels through the spinal canal is of interest as a potential indicator of CSF system pressure and compliance, both of which may play a role in the development of craniospinal diseases. However, measurement of CSF velocity wave speed (VWS) has eluded researchers primarily due to either a lack of access to CSF velocity measurements or poor temporal resolution. Here, we present a CSF VWS measurement methodology using a novel MR sequence that acquires unsteady velocity measurements during the cardiac cycle with a time interval < 10 ms. Axial CSF velocity measurements were obtained in the sagittal plane of the cervical spinal region on three subjects referred for an MRI scan without craniospinal disorders. CSF VWS was estimated by using the time shift identified by the maximum velocity and maximum temporal velocity gradient during the cardiac cycle. Based on the maximum velocity gradient, the mean VWS in the three cases was calculated to be 4.6 m/s (standard deviation 1.7 m/s, p < 0.005) during systolic acceleration. VWS computed using maximum velocity alone was not statistically significant for any of the three cases. The measurements of VWS are close in magnitude to previously published values. The methodology represents a new technique that can be used to measure VWS in the spinal canal noninvasively. Further research is required to both validate the measurements and determine clinical significance.

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

    PubMed

    Christensen, M; Sparre-Ulrich, A H; Hartmann, B; Grevstad, U; Rosenkilde, M M; Holst, J J; Vilsbøll, T; Knop, F K

    2015-11-01

    Treatment with liraglutide leads to weight loss. We investigated whether blood-to-cerebrospinal fluid (CSF) transfer of liraglutide occurs, and if so, whether it associates with clinical weight loss following liraglutide treatment in humans. We performed lumbar puncture and blood sampling in eight patients with type 2 diabetes (mean (range)): age 63 (54-79) years; actual body weight: 90 (75-118) kg treated with 1.8 mg liraglutide for 14 (5-22) months and with a treatment-induced weight loss of 8.4 (7-11) kg. We measured liraglutide in plasma and CSF with a radioimmunoassay specific for the N-terminus of the GLP-1 moiety of liraglutide. Mean plasma liraglutide was 31 (range: 21-63) nmol l(-1). The mean CSF-liraglutide concentration was 6.5 (range: 0.9-13.9) pmol l(-1). Ratio of CSF: plasma-liraglutide concentrations was 0.02 (range: 0.07-0.002)% and plasma liraglutide did not correlate with CSF-liraglutide levels (P=0.67). Body weight loss tended to correlate with plasma-liraglutide levels (P=0.06), but not with CSF-liraglutide levels (P=0.69). In conclusion, we measured very low concentrations of liraglutide in CSF, and the levels of CSF liraglutide did not correlate with the actual clinical weight loss in these patients. The amount of liraglutide in plasma tended to correlate with the clinical weight loss.

  8. In Vivo Imaging of Lymphatic Drainage of Cerebrospinal Fluid in Mouse

    PubMed Central

    2013-01-01

    Background Mouse models are commonly used to study central nervous system disorders, in which cerebrospinal fluid (CSF) drainage may be disturbed. However, mouse CSF drainage into lymphatics has not been thoroughly characterized. We aimed to image this using an in vivo approach that combined quantum dot fluorescent nanoparticles with hyperspectral imaging. Findings Quantum dot 655 was injected into the CSF of the cisterna magna in seven mice and visualized by in vivo hyperspectral imaging at time points 20 and 40 min, 1, 2, and 6 h after injection. In controls (n = 4), quantum dots were applied directly onto intact dura mater covering the cisterna magna. After imaging, lymph nodes in the neck were harvested and processed post-mortem for histological analysis. After injection into the CSF, quantum dot signal was detected in vivo in submandibular lymph nodes of all mice studied as early as 20 min, but not in controls. Post-mortem gross and histological examination of lymph nodes confirmed in vivo observations. Conclusions Non-invasive in vivo hyperspectral imaging is a useful tool to study CSF lymphatic drainage and is relevant to understanding this pathway in CNS disease models. PMID:24360130

  9. Human Neurocysticercosis: Comparison of Different Diagnostic Tests Using Cerebrospinal Fluid

    PubMed Central

    Michelet, Lorraine; Fleury, Agnès; Sciutto, Edda; Kendjo, Eric; Fragoso, Gladis; Paris, Luc; Bouteille, Bernard

    2011-01-01

    Neurocysticercosis (NC), caused by the larval stage of Taenia solium, is one of the most common parasitic diseases of the central nervous system. The diagnosis of NC is mostly based on costly brain neuroimaging (computed tomography and/or nuclear magnetic resonance), which is rarely accessible in most affected areas. The most sensitive and specific tools for NC diagnosis are imagery techniques. The identification of specific antibodies and antigens is currently used only to support NC diagnosis due to their limited specificity and sensitivity. This study was performed to compare immunodiagnostic assays (antibody detection by enzyme-linked immunosorbent assay [ELISA] and enzyme-linked immunoelectrotransfer blotting [EITB] and HP10 antigen detection by ELISA) with the detection of parasite DNA by PCR amplification of a repetitive element of the parasite genome in the cerebrospinal fluid (CSF) of 121 radiologically and clinically characterized NC patients. Patients were divided into six groups according to the stage of the parasites and their localization. The CSF cellularity of each patient was also recorded. When all patients were considered, PCR exhibited the highest sensitivity (95.9%) and variable specificity (80% or 100%) depending on the controls used. The sensitivities of antibody detection by ELISA and EITB were not significantly different, and ELISA identified HP10 antigen mostly when vesicular cysticerci were located in the subarachnoideal basal cisterns. These results can help in the selection of different individual assays or combinations of assays to be used in NC diagnosis according to different requirements. PMID:21068283

  10. Sandwich Wound Closure Reduces the Risk of Cerebrospinal Fluid Leaks in Posterior Fossa Surgery

    PubMed Central

    Heymanns, Verena; Oseni, Abidemi W.; Alyeldien, Ameer; Maslehaty, Homajoun; Parvin, Richard; Scholz, Martin

    2016-01-01

    Posterior fossa surgery is demanding and hides a significant number of obstacles starting from the approach to the wound closure. The risk of cerebrospinal fluid (CSF) leakage in posterior fossa surgery given in the literature is around 8%. The present study aims to introduce a sandwich closure of the dura in posterior fossa surgery, which reduces significantly the number of CSF leaks (3.8%) in the patients treated in our department. Three hundred and ten patients treated in our hospital in the years 2009-2013 for posterior fossa pathologies were retrospectively evaluated. The dura closure method was as following: lyophilized dura put under the dura and sealed with fibrin glue and sutures, dura adapting stitches, TachoSil® (Takeda Pharma A/S, Roskilde, Denmark), Gelfoam® (Pfizer Inc., New York, NY, USA) and polymethylmethacrylate (osteoclastic craniotomy). The incidence of postsurgical complications associated with the dural closure like CSF leakage, infections, bleeding is evaluated. Only 3.8% of patients developed CSF leakage and only 0.5% needed a second surgery for CSF leakage closure. Two percent had a cerebellar bleeding with no need for re-operation and 3% had a wound infection treated with antibiotics. The sandwich wound closure we are applying for posterior fossa surgery in our patients correlates with a significant reduction of CSF leaks compared to the literature. PMID:27478578

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

    PubMed Central

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

    2016-01-01

    Natural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg·L−1 for male rats and 40 mg·L−1 for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L−1 NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L−1 NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function. PMID:27247806

  12. Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

    PubMed Central

    Babić, Mirjana; Švob Štrac, Dubravka; Mück-Šeler, Dorotea; Pivac, Nela; Stanić, Gabrijela; Hof, Patrick R.; Šimić, Goran

    2014-01-01

    Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid β1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed. PMID:25165049

  13. Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

    PubMed Central

    Granberg, Tobias; Martola, Juha; Li, Xiaozhen; Shams, Mana; Fereshtehnejad, Seyed-Mohammad; Cavallin, Lena; Aspelin, Peter; Kristoffersen-Wiberg, Maria; Wahlund, Lars-Olof

    2015-01-01

    Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease (p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs. PMID:26661151

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

    PubMed

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

    2013-05-17

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

  15. Associations between a locus downstream DRD1 gene and cerebrospinal fluid dopamine metabolite concentrations in psychosis.

    PubMed

    Andreou, Dimitrios; Söderman, Erik; Axelsson, Tomas; Sedvall, Göran C; Terenius, Lars; Agartz, Ingrid; Jönsson, Erik G

    2016-04-21

    Dopamine activity, mediated by the catecholaminergic neurotransmitter dopamine, is prominent in the human brain and has been implicated in schizophrenia. Dopamine targets five different receptors and is then degraded to its major metabolite homovanillic acid (HVA). We hypothesized that genes encoding dopamine receptors may be associated with cerebrospinal fluid (CSF) HVA concentrations in patients with psychotic disorder. We searched for association between 67 single nucleotide polymorphisms (SNPs) in the five dopamine receptor genes i.e., DRD1, DRD2, DRD3, DRD4 and DRD5, and the CSF HVA concentrations in 74 patients with psychotic disorder. Nominally associated SNPs were also tested in 111 healthy controls. We identified a locus, located downstream DRD1 gene, where four SNPs, rs11747728, rs11742274, rs265974 and rs11747886, showed association with CSF HVA concentrations in psychotic patients. The associations between rs11747728, which is a regulatory region variant, and rs11742274 with HVA remained significant after correction for multiple testing. These associations were restricted to psychotic patients and were absent in healthy controls. The results suggest that the DRD1 gene is implicated in the pathophysiology of psychosis and support the dopamine hypothesis of schizophrenia.

  16. HIV Migration Between Blood and Cerebrospinal Fluid or Semen Over Time

    PubMed Central

    Chaillon, Antoine; Gianella, Sara; Wertheim, Joel O.; Richman, Douglas D.; Mehta, Sanjay R.; Smith, David M.

    2014-01-01

    Previous studies reported associations between neuropathogenesis and human immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF) and between sexual transmission and human immunodeficiency virus type 1 (HIV) compartmentalization in semen. It remains unclear, however, how compartmentalization dynamics change over time. To address this, we used statistical methods and Bayesian phylogenetic approaches to reconstruct temporal dynamics of HIV migration between blood and CSF and between blood and the male genital tract. We investigated 11 HIV-infected individuals with paired semen and blood samples and 4 individuals with paired CSF and blood samples. Aligned partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral compartmentalization, using tree-based and distance-based methods; and (3) analysis of migration events, using a discrete Bayesian asymmetric phylogeographic approach of diffusion with Markov jump counts estimation. Finally, we evaluated potential correlates of viral gene flow across anatomical compartments. We observed bidirectional replenishment of viral compartments and asynchronous peaks of viral migration from and to blood over time, suggesting that disruption of viral compartment is transient and directionally selected. These findings imply that viral subpopulations in anatomical sites are an active part of the whole viral population and that compartmental reservoirs could have implications in future eradication studies. PMID:24302756

  17. Low-voltage DEP microsystem for submicron particle manipulation in artificial cerebrospinal fluid.

    PubMed

    Miled, Mohamed Amine; Sawan, Mohamad

    2013-01-01

    In this paper, we present a new low voltage biochip for micro and nanoparticle separation. The proposed system is designed to detect the concentration of particles after being separated through reconfigurable DEP-based electrode architecture. The described system in this work is focusing on the particle frequency dependent separation. Experimental results in artificial cerebrospinal fluid (ACSF) show that each particle has its own crossover frequency. Thus based on the crossover frequency, particles are attracted to the electrode's surface, while others are pushed away. Five different particles are tested with different diameters in the range of 500 nm to 4 µm. All separation process is controlled by a CMOS chip fabricated using 0.18 µm technology from TSMC and powered with 3.3 V. Efficient particle separation is observed with low voltage, below 3.3V unlike other techniques in the range of kV. The proposed platform includes an advanced PDMS based assembly technique for fast testing and prototyping in addition to reconfigurable electrode architecture.

  18. Flowing cerebrospinal fluid in normal and hydrocephalic states: Appearance on MR images

    SciTech Connect

    Bradley, W.G.; Kortman, K.E.; Burgoyne, B.; Eng, D.

    1986-06-01

    The signal intensity of the cerebrospinal fluid (CSF) in the cerebral aqueduct and lateral ventricles on magnetic resonance (MR) images was evaluated in 16 healthy individuals and in 32 patients with various forms of hydrocephalus (20 with chronic normal pressure hydrocephalus (NPH), seven with acute communicating hydrocephalus, and five with hydrocephalus ex vacuo (atrophy)). The low signal intensity frequently observed in the cerebral aqueduct is believed to reflect the pulsatile motion of CSF, which is related to the cardiac cycle. While this aqueductal flow void phenomenon can be observed in healthy individuals, it is most pronounced in patients with chronic, communicating NPH; is less evident in patients with acute, communicating hydrocephalus and is least evident in patients with atrophy. Ventricular compliance is known to be essentially normal in atrophy, mildly decreased in acute, communicating hydrocephalus; and severely decreased in NPH. The degree of aqueductal signal loss is believed to reflect the velocity of the pulsatile CSF motion, which in turn depends on the relative ventricular compliance and surface area.

  19. Quantitative Analysis of Cerebrospinal Fluid Pressure Gradients in Healthy Volunteers and Patients with Normal Pressure Hydrocephalus

    PubMed Central

    HAYASHI, Naokazu; MATSUMAE, Mitsunori; YATSUSHIRO, Satoshi; HIRAYAMA, Akihiro; ABDULLAH, Afnizanfaizal; KURODA, Kagayaki

    2015-01-01

    Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image. PMID:26226976

  20. The UKNEQAS scheme for cerebrospinal fluid haem pigments: a paradigm for service improvement.

    PubMed

    Beetham, Robert; Egner, William; Patel, Dina

    2011-11-01

    We describe the programme of an established External Quality Assurance (EQA) provider and a Specialist Advisory Group (SAG) to develop a successful EQA scheme for cerebrospinal fluid (CSF) haem pigments as an example of a professionally led, unfunded initiative with the real potential to benefit patients. Within three years, we had assured sample stability, stoichiometry, and published best practice guidelines, enabling both analytical results and interpretation to be assessed and reported with an educative summary of the desired responses. Misclassification scoring of analysis and interpretation was introduced. Following audit, guidelines were modified and republished. The outcomes were as follows: Participant numbers increased from 63 at inception to 150 10 years later; The percentage of participants using visual inspection, a poor practice indicator, decreased from 27% to less than 1%; In all, 94-100% of participants consistently detected minor increases in bilirubin over the last four years of the scheme; More than 93% of participants were able to interpret analytical results linked to straightforward clinical scenarios; Misclassification scoring demonstrated that more complex scenarios repeatedly posed problems and is the next challenge to address. Scheme success is attributed to the experience of the operator and the formation of a voluntary expert advisory group, with both concerned to advance science and patient safety and thus contribute unpaid time and effort in order to succeed. In times of fiscal constraint, such resource may not be so readily available, yet is a vital part of continuous quality improvement for the benefit of patients.

  1. Assessment of cerebrospinal fluid outflow conductance using an adaptive observer--experimental and clinical evaluation.

    PubMed

    Andersson, K; Manchester, I R; Andersson, N; Shiriaev, A; Malm, J; Eklund, A

    2007-11-01

    Idiopathic normal pressure hydrocephalus (INPH) patients have a disturbance in the dynamics of the cerebrospinal fluid (CSF) system. The outflow conductance, C, of the CSF system has been suggested to be prognostic for positive outcome after treatment with a CSF shunt. All current methods for estimation of C have drawbacks; these include lack of information on the accuracy and relatively long investigation times. Thus, there is a need for improved methods. To accomplish this, the theoretical framework for a new adaptive observer (OBS) was developed which provides real-time estimation of C. The aim of this study was to evaluate the OBS method and to compare it with the constant pressure infusion (CPI) method. The OBS method was applied to data from infusion investigations performed with the CPI method. These consisted of repeated measurements on an experimental set-up and 30 patients with suspected INPH. There was no significant difference in C between the CPI and the OBS method for the experimental set-up. For the patients there was a significant difference, -0.84+/-1.25 microl (s kPa)(-1), mean +/- SD (paired sample t-test, p<0.05). However, such a difference is within clinically acceptable limits. This encourages further development of this new real-time approach for estimation of the outflow conductance.

  2. Intracranial pressure and conductance to outflow of cerebrospinal fluid in normal-pressure hydrocephalus.

    PubMed

    Børgesen, S E; Gjerris, F; Sørensen, S C

    1979-04-01

    Forty patients with clinical evidence of normal-pressure hydrocephalus were studied by monitoring intraventricular pressure during a 24-hour period, and by a lumboventricular perfusion test for measurement of the conductance to outflow of cerebrospinal fluid (CSF). The purpose of the study was to investigate whether there is a relationship between intraventricular pressure and conductance to outflow of CSF, and whether it is possible to use the results from pressure monitoring in the selection of patients who may be expected to benefit from shunting therapy. The conductance to outflow was used as an evaluation factor in the selection of patients to be treated by a shunt. The conductance to CSF outflow differed by twelvefold between the lowest and highest values. The level of resting intraventricular pressure was within normal limits in all patients. Accordingly, there was no evidence of a relationship between conductance to outflow and intraventricular pressure. So-called B-waves were seen more frequently in patients with decreased conductance to outflow, but were also present in patients with high conductance to outflow. Therefore, the presence of B-waves does not imply a low conductance to outflow of CSF.

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

    SciTech Connect

    Millar, W.T.; Barrett, A. )

    1990-02-01

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

  4. An alternative method of chronic cerebrospinal fluid collection via the cisterna magna in conscious rhesus monkeys.

    PubMed

    Gilberto, David B; Zeoli, Angela H; Szczerba, Peter J; Gehret, John R; Holahan, Marie A; Sitko, Gary R; Johnson, Colena A; Cook, Jacquelynn J; Motzel, Sherri L

    2003-07-01

    Models of chronic cerebrospinal fluid (CSF) collection previously have been established for nonhuman primates and canines; many of these methods implement stainless-steel cannulas into the lateral or 4th ventricles or catheters into the cerebral or spinal subarachnoid space. These models have proved successful and reliable but unfortunately require invasive techniques to pass through the skull or require a laminectomy to enter the spinal subarachnoid space, involve the use of expensive and highly specialized stereotaxic equipment for the precise placement of the implants, and may require exteriorized hardware which is cumbersome to maintain and unaesthetic. The model we developed for the rhesus monkey allows for direct access to CSF outflow from the cisterna magna by using a 3.5-French fenestrated silicone catheter which was placed 1.0 cm into the cisterna. The catheter was attached to a titanium port placed subcutaneously between the scapulae to permit easy access for sampling CSF in a conscious, chaired rhesus monkey. We currently have instrumented animals from which we have consistently collected CSF for over 18 months. This novel, economical, less-invasive method permits chronic, reliable collection of CSF in conscious rhesus monkeys and has the additional advantages that the model is easier to maintain and more aesthetic.

  5. The neurochemical markers in cerebrospinal fluid to differentiate between aseptic and tuberculous meningitis.

    PubMed

    Qureshi, G A; Baig, S M; Bednar, I; Halawa, A; Parvez, S H

    1998-02-01

    In this study, the use of neurochemical markers in patients with aseptic and tuberculous meningitis has been investigated. The cerebrospinal fluid levels of amino acids, nitrite (a metabolite of nitric oxide), vitamin B12 and homocysteine were quantitated in both groups of patients. Among the amino acids, aspartic acid and glutamic acid both excitatory amino acid, GABA, glycine and tryptophan were all significantly increased in both patient groups whereas decreased level of taurine and increased level of phenylalanine were only found in patients with tuberculous meningitis. The levels of nitrite and its precursor arginine were significantly higher in patients with tuberculous meningitis whereas unchanged levels were found in patients with aseptic meningitis. A significantly increased homocysteine level and a decreased level of vitamin B12 were found only in patients with tuberculous meningitis whereas unchanged levels were found in patients with aseptic meningitis. This indicates that patients with tuberculous meningitis are particularly prone to vitamin B12 deficiency resulting into increased level of HC, and involvement of free radical showing the importance of these biological markers for promoting the possibility for the design of therapeutic approach.

  6. PBPK model of methotrexate in cerebrospinal fluid ventricles using a combined microdialysis and MRI acquisition.

    PubMed

    Brandhonneur, Nolwenn; Noury, Fanny; Bruyère, Arnaud; Saint-Jalmes, Hervé; Le Corre, Pascal

    2016-07-01

    The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model. MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data. The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results. The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases.

  7. Bioanalysis of acetylcarnitine in cerebrospinal fluid by HILIC-mass spectrometry.

    PubMed

    Holder, Brian R; McNaney, Colleen A; Luchetti, David; Schaeffer, Eric; Drexler, Dieter M

    2015-09-01

    Acetyl-L-carnitine (ALCAR) is a potential biomarker for the modulation of brain neurotransmitter activity, but is also present in cerebrospinal fluid (CSF). Recent studies have utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) based assays to detect and quantify ALCAR within biofluids such as urine, plasma and serum, using various sample pretreatment procedures. In order to address the need to quantify ALCAR in CSF on a high-throughput scale, a new and simple HILIC-MS/MS assay has been successfully developed and validated. For rapid analysis, CSF sample pretreatment was performed via 'dilute and shoot' directly onto an advanced HILIC column prior to MS/MS detection. This newly developed HILIC-MS/MS assay shows good recoveries of ALCAR without the need for chemical derivatization and multistep sample extraction procedures. The employment of this assay is suitable for the high-throughput bioanalysis and quantification of ALCAR within the CSF of various animal models and human clinical studies.

  8. Contemporary Approach to the Diagnosis and Management of Cerebrospinal Fluid Rhinorrhea

    PubMed Central

    Mathias, Tiffany; Levy, Joshua; Fatakia, Adil; McCoul, Edward D.

    2016-01-01

    Background: Cerebrospinal fluid (CSF) rhinorrhea, when left untreated, can lead to meningitis and other serious complications. Treatment traditionally has entailed an open craniotomy, although the paradigm has now evolved to encompass endoscopic procedures. Trauma, both accidental and iatrogenic, causes the majority of leaks, and trauma involving skull base and facial fractures is most likely to cause CSF rhinorrhea. Diagnosis is aided by biochemical assay and imaging studies. Methods: We reviewed the literature and summarized current practice regarding the diagnosis and management of CSF rhinorrhea. Results: Management of CSF leaks is dictated by the nature of the fistula, its location, and flow volume. Control of elevated intracranial pressure may require medical therapy or shunt procedures. Surgical reconstruction utilizes a graduated approach involving vascularized, nonvascularized, and adjunctive techniques to achieve closure of the CSF leak. Endoscopic techniques have an important role in select cases. Conclusion: An active surgical approach to closing CSF leaks may provide better long-term outcomes in some patients compared to more conservative management. PMID:27303222

  9. Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

    PubMed Central

    Perez-Alcazar, Marta; Culley, Georgia; Lyckenvik, Tim; Mobarrez, Kristoffer; Bjorefeldt, Andreas; Wasling, Pontus; Seth, Henrik; Asztely, Frederik; Harrer, Andrea; Iglseder, Bernhard; Aigner, Ludwig; Hanse, Eric; Illes, Sebastian

    2016-01-01

    For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling. PMID:26973467

  10. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

    PubMed

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

    2016-10-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  11. Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for Leptomeningeal Metastasis

    PubMed Central

    Zhang, Zhen; Shi, Qiang; Hao, Jing; Zhao, Na; Liu, Zhijie

    2017-01-01

    Cerebrospinal fluid (CSF) cytology has low sensitivity for leptomeningeal metastasis (LM); thus, new markers are needed to improve the diagnostic accuracy of LM. We measured carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) in paired samples of CSF and serum from patients with LM and patients with nonmalignant neurological diseases (NMNDs) as controls. Receiver operating curve analysis was performed to assess their diagnostic accuracy for LM. In patients with NMNDs, CEA and CYFRA 21-1 levels in the CSF were significantly lower than the serum levels. In patients with LM, there was no significant difference between the CSF and serum CEA levels, whereas the CYFRA 21-1 levels were significantly higher in the CSF than the serum. CSF/serum quotients of CYFRA 21-1 were higher than those of CEA in patients with LM and patients with NMNDs. CSF CYFRA 21-1 and CSF/serum quotient of CYFRA 21-1 had high accuracy for differentiating LM from NMNDs that was similar to CSF CEA and CSF/serum quotient of CYFRA 21-1, whereas serum CYFRA 21-1 is of poor diagnostic value. Measurement of CSF CYFRA 21-1 should not be overlooked in patients with suspected LM, even if the serum CYFRA 21-1 level is within normal limits. PMID:28298807

  12. The cerebrospinal fluid HIV risk score for assessing central nervous system activity in persons with HIV.

    PubMed

    Hammond, Edward R; Crum, Rosa M; Treisman, Glenn J; Mehta, Shruti H; Marra, Christina M; Clifford, David B; Morgello, Susan; Simpson, David M; Gelman, Benjamin B; Ellis, Ronald J; Grant, Igor; Letendre, Scott L; McArthur, Justin C

    2014-08-01

    Detectable human immunodeficiency virus (HIV) RNA in the cerebrospinal fluid (CSF) is associated with central nervous system (CNS) complications. We developed the CSF HIV risk score through prediction modeling to estimate the risk of detectable CSF HIV RNA (threshold >50 copies/mL) to help identify persons who might benefit most from CSF monitoring. We used baseline data from 1,053 participants receiving combination antiretroviral therapy who were enrolled in the 6-center, US-based CNS HIV Antiretroviral Therapy Effects Research (CHARTER) prospective cohort in 2004-2007. Plasma HIV RNA, CNS penetration effectiveness, duration of combination antiretroviral therapy, medication adherence, race, and depression status were retained correlates of CSF HIV RNA, displaying good discrimination (C statistic = 0.90, 95% confidence interval (CI): 0.87, 0.93) and calibration (Hosmer-Lemeshow P = 0.85). The CSF HIV risk score ranges from 0 to 42 points, with a mean of 15.4 (standard deviation, 7.3) points. At risk scores greater than 25, the probability of detecting CSF HIV RNA was at least 42.9% (95% CI: 36.6, 49.6). For each 1-point increase, the odds of detecting CSF HIV RNA increased by 26% (odds ratio = 1.26, 95% CI: 1.21, 1.31; P < 0.01). The risk score correlates with detection of CSF HIV RNA. It represents an advance in HIV management and monitoring of CNS effects, providing a potentially useful tool for clinicians.

  13. The Cerebrospinal Fluid HIV Risk Score for Assessing Central Nervous System Activity in Persons With HIV

    PubMed Central

    Hammond, Edward R.; Crum, Rosa M.; Treisman, Glenn J.; Mehta, Shruti H.; Marra, Christina M.; Clifford, David B.; Morgello, Susan; Simpson, David M.; Gelman, Benjamin B.; Ellis, Ronald J.; Grant, Igor; Letendre, Scott L.; McArthur, Justin C.

    2014-01-01

    Detectable human immunodeficiency virus (HIV) RNA in the cerebrospinal fluid (CSF) is associated with central nervous system (CNS) complications. We developed the CSF HIV risk score through prediction modeling to estimate the risk of detectable CSF HIV RNA (threshold >50 copies/mL) to help identify persons who might benefit most from CSF monitoring. We used baseline data from 1,053 participants receiving combination antiretroviral therapy who were enrolled in the 6-center, US-based CNS HIV Antiretroviral Therapy Effects Research (CHARTER) prospective cohort in 2004–2007. Plasma HIV RNA, CNS penetration effectiveness, duration of combination antiretroviral therapy, medication adherence, race, and depression status were retained correlates of CSF HIV RNA, displaying good discrimination (C statistic = 0.90, 95% confidence interval (CI): 0.87, 0.93) and calibration (Hosmer-Lemeshow P = 0.85). The CSF HIV risk score ranges from 0 to 42 points, with a mean of 15.4 (standard deviation, 7.3) points. At risk scores greater than 25, the probability of detecting CSF HIV RNA was at least 42.9% (95% CI: 36.6, 49.6). For each 1-point increase, the odds of detecting CSF HIV RNA increased by 26% (odds ratio = 1.26, 95% CI: 1.21, 1.31; P < 0.01). The risk score correlates with detection of CSF HIV RNA. It represents an advance in HIV management and monitoring of CNS effects, providing a potentially useful tool for clinicians. PMID:24966216

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

    PubMed

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

    2015-10-01

    Type 1 narcolepsy is caused by a loss of hypocretin (orexin) signaling in the brain. Genetic data suggests the disorder is caused by an autoimmune attack on hypocretin producing neurons in hypothalamus. This hypothesis has however not yet been confirmed by consistent findings of autoreactive antibodies or T-cells in patient samples. One explanation for these negative results may be that the autoimmune process is no longer active when patients present to the clinic. With increasing awareness in recent years, more and more patients have been diagnosed closer and closer to disease onset. In this study, we tested whether an active immune process in the brain could be detected in these patients, as reflected by increased cytokine levels in the cerebrospinal fluid (CSF). Using multiplex analysis, we measured the levels of 51 cytokines and chemokines in the CSF of 40 type 1 narcolepsy patients having varying disease duration. For comparison, we used samples from 9 healthy controls and 9 patients with other central hypersomnia. Cytokine levels did not differ significantly between controls and patients, even in 5 patients with disease onset less than a month prior to CSF sampling.

  15. Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease

    PubMed Central

    Sweeney, Melanie D; Sagare, Abhay P; Zlokovic, Berislav V

    2015-01-01

    Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth muscle cells), glial cells (astrocytes and microglia), and neurons. Thus, identifying and integrating biomarkers of the NVU cell-specific responses and injury with established AD biomarkers, amyloid-β (Aβ) and tau, has a potential to contribute to better understanding of the disease process in dementias including AD. Here, we discuss the existing literature on cerebrospinal fluid biomarkers of the NVU cell-specific responses during early stages of dementia and AD. We suggest that the clinical usefulness of established AD biomarkers, Aβ and tau, could be further improved by developing an algorithm that will incorporate biomarkers of the NVU cell-specific responses and injury. Such biomarker algorithm could aid in early detection and intervention as well as identify novel treatment targets to delay disease onset, slow progression, and/or prevent AD. PMID:25899298

  16. Measurement of cerebrospinal fluid formation and absorption by ventriculo-cisternal perfusion: what is really measured?

    PubMed Central

    Orešković, Darko; Klarica, Marijan

    2014-01-01

    The generally accepted hypothesis on cerebrospinal fluid (CSF) hydrodynamics suggests that CSF is actively formed mainly by choroid plexuses, circulates unidirectionally along the brain ventricles and subarachnoid space, and is passively absorbed mainly into the dural venous sinuses. CSF formation rate (Vf) has been extensively studied using the ventriculo-cisternal perfusion technique and the results have been used as the key evidence confirming the mentioned hypothesis. This method and the equation for Vf calculation are based on the assumption that the dilution of the indicator substance is a consequence of the newly formed CSF, ie, that a higher CSF formation rate will result in a higher degree of dilution. However, it has been experimentally shown that the indicator substance dilution inside the CSF system does not occur because of a “newly formed” CSF, but as consequence of a number of other factors (departure of substances into the surrounding tissue, flowing around the collecting cannula into the cortical and spinal subarachnoid space, departure into the contralateral ventricle, etc). This technique allows “calculation” of the CSF formation even in dead animals, in an in vitro model, and in any other part of the CSF system outside the ventricles that is being perfused. Therefore, this method is indirect and any dilution of the indicator substance in the perfusate caused by other reasons would result in questionable and often contradictory conclusions regarding CSF formation rates. PMID:25165046

  17. The predictive value of cerebrospinal fluid tap-test in normal pressure hydrocephalus.

    PubMed

    Damasceno, B P; Carelli, E F; Honorato, D C; Facure, J J

    1997-06-01

    Eighteen patients (mean age of 66.5 years) with normal pressure hydrocephalus (NPH) underwent a ventriculo-peritoneal shunt surgery. Prior to operation a cerebrospinal fluid tap-test (CSF-TT) was performed with measurements of gait pattern and psychometric functions (memory, visuo-motor speed and visuo-constructive skills) before and after the removal of 50 ml CSF by lumbar puncture (LP). Fifteen patients improved and 3 were unchanged after surgery. Short duration of disease, gait disturbance preceding mental deterioration, wide temporal horns and small sulci on CT-scan were associated with good outcome after shunting. There was a good correlation between the results of CSF-TT and shunt surgery (chi 2 = 4.11, phi = 0.48, p < 0.05), with gait test showing highest correlation (r = 0.99, p = 0.01). In conclusion, this version of CSF-TT proved to be an effective test to predict improvement after shunting in patients with NPH.

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

    PubMed Central

    2012-01-01

    There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of β-endorphin (β-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of β-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose β-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of β-END, independence of peripheral versus central levels, central β-END migration over considerable distances, behavioral effects of β-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain. PMID:22883598

  19. Role of Cerebrospinal Fluid Biomarkers in Clinical Trials for Alzheimer's Disease Modifying Therapies

    PubMed Central

    Ryoo, Na-Young; Shin, Dong Wun; Trojanowski, John Q

    2014-01-01

    Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) Aβ1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the PMID:25598657

  20. Leptin Levels Are Negatively Correlated with 2-Arachidonoylglycerol in the Cerebrospinal Fluid of Patients with Osteoarthritis

    PubMed Central

    Nicholson, James; Azim, Syed; Rebecchi, Mario J.; Galbavy, William; Feng, Tian; Reinsel, Ruth; Rizwan, Sabeen; Fowler, Christopher J.; Benveniste, Helene; Kaczocha, Martin

    2015-01-01

    Background There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. Methodology/Principal Findings Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography – mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman’s ρ -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. Conclusions/Significance In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior. PMID:25835291

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

    PubMed

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

    2013-04-01

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

  2. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

    SciTech Connect

    Miller, B.E.; Lipman, J.J.; Byrne, W.L.

    1987-12-07

    Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

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

    PubMed Central

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

    2015-01-01

    Type 1 Narcolepsy is caused by a loss of hypocretin (orexin) signaling in the brain. Genetic data suggests the disorder is caused by an autoimmune attack on hypocretin producing neurons in hypothalamus. This hypothesis has however not yet been confirmed by consistent findings of autoreactive antibodies or T-cells in patient samples. One explanation for these negative results may be that the autoimmune process is no longer active when patients present to the clinic. With increasing awareness in recent years, more and more patients have been diagnosed closer and closer to disease onset. In this study, we tested whether an active immune process in the brain could be detected in these patients, as reflected by increased cytokine levels in the cerebrospinal fluid (CSF). Using multiplex analysis, we measured the levels of 51 cytokines and chemokines in the CSF of 40 Type 1 Narcolepsy patients having varying disease duration. For comparison, we used samples from 9 healthy controls and 9 patients with other central hypersomnia. Cytokine levels did not differ significantly between controls and patients, even in 5 patients with disease onset less than a month prior to CSF sampling. PMID:25771509

  4. Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy.

    PubMed

    Nishino, S; Ripley, B; Overeem, S; Nevsimalova, S; Lammers, G J; Vankova, J; Okun, M; Rogers, W; Brooks, S; Mignot, E

    2001-09-01

    Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.

  5. Effect of inhaled nitric oxide on cerebrospinal fluid and blood nitrite concentrations in newborn lambs

    PubMed Central

    Conahey, George R.; Power, Gordon G.; Hopper, Andrew O.; Terry, Michael H.; Kirby, Laura S.; Blood, Arlin B.

    2009-01-01

    Inhaled nitric oxide (iNO) has many extrapulmonary effects. As the half-life of NO in blood is orders of magnitude less than the circulation time from lungs to the brain, the mediator of systemic effects of iNO is unknown. We hypothesized that concentrations of nitrite, a circulating byproduct of NO with demonstrated NO bioactivity, would increase in blood and cerebrospinal fluid (CSF) during iNO therapy. iNO (80ppm) was given to six newborn lambs and results compared to six control lambs. Blood and CSF nitrite concentrations increased two-fold in response to iNO. cGMP increased in blood but not CSF suggesting brain guanylate cyclase activity was not increased. When sodium nitrite was infused intravenously blood and CSF nitrite levels increased within 10 min and reached similar levels of 14.6±1.5 µM after 40 min. The reactivity of nitrite in hemoglobin-free brain homogenates was investigated, with the findings that nitrite did not disappear nor did measurable amounts of s-nitroso, n-nitroso, or iron-nitrosyl-species appear. We conclude that although nitrite diffuses freely between blood and CSF, due to its lack of reactivity in the brain, nitrite’s putative role as the mediator of the systemic effects of iNO is limited to intravascular reactions. PMID:18535482

  6. Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

    PubMed

    Shams, Sara; Granberg, Tobias; Martola, Juha; Li, Xiaozhen; Shams, Mana; Fereshtehnejad, Seyed-Mohammad; Cavallin, Lena; Aspelin, Peter; Kristoffersen-Wiberg, Maria; Wahlund, Lars-Olof

    2016-03-01

    Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer's disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood-brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer's patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer's disease (p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

  7. Massive Cerebrospinal Fluid Replacement Reduces Delayed Cerebral Vasospasm After Embolization of Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Geng, Liming; Ma, Fei; Liu, Yun; Mu, Yanchun; Zou, Zhongmin

    2016-07-10

    BACKGROUND Delayed cerebral vasospasm (DCVS) following aneurismal subarachnoid hemorrhage (SAH) is a leading cause of poor prognosis and death in SAH patients. Effective management to reduce DCVS is needed. A prospective controlled trial was conducted to determine if massive cerebrospinal fluid (CSF) replacement (CR) could reduce DCVS occurrence and improve the clinical outcome after aneurysmal SAH treated with endovascular coiling. MATERIAL AND METHODS Patients treated with endovascular coiling after aneurysmal SAH were randomly divided into a control group receiving regular therapy alone (C group, n=42) and a CSF replacement group receiving an additional massive CSF replacement with saline (CR group, n=45). CSF examination, head CT, DCVS occurrence, cerebral infarction incidence, Glasgow Outcome Scale prognostic score, and 1-month mortality were recorded. RESULTS The occurrence of DCVS was 30.9% in the C group and 4.4% in the CR group (P<0.005). The cerebral infarction incidences in the C and CR groups were 19.0% and 2.2% (P<0.05), respectively, 1 month after the treatments. Mortality was not significantly different between the 2 groups during the follow-up period. CONCLUSIONS Massive CR after embolization surgery for aneurysmal SAH can significantly reduce DCVS occurrence and effectively improve the outcomes.

  8. Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor.

    PubMed

    Schmidt, André P; Böhmer, Ana E; Hansel, Gisele; Soares, Félix A; Oses, Jean P; Giordani, Alex T; Posso, Irimar P; Auler, José Otávio C; Mendes, Florentino F; Félix, Elaine A; Portela, Luís V; Souza, Diogo O

    2015-11-01

    Labor pain has been reported as a severe pain and can be considered as a model of acute visceral pain. It is well known that extracellular purines have an important role in pain signaling in the central nervous system. This study analyzes the relationship between extracellular purines and pain perception during active labor. A prospective observational study was performed. Cerebrospinal fluid (CSF) levels of the purines and their metabolites were compared between women at term pregnancy with labor pain (n = 49) and without labor pain (Caesarian section; n = 47). Control groups (healthy men and women without chronic or acute pain-n = 40 and 32, respectively) were also investigated. The CSF levels of adenosine were significantly lower in the labor pain group (P = 0.026) and negatively correlated with pain intensity measured by a visual analogue scale (r = -0.48, P = 0.0005). Interestingly, CSF levels of uric acid were significantly higher in healthy men as compared to women. Additionally, pregnant women showed increased CSF levels of ADP, GDP, adenosine and guanosine and reduced CSF levels of AMP, GTP, and uric acid as compared to non-pregnant women (P < 0.05). These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain.

  9. Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases.

    PubMed

    Ichinose, Kunihiro; Arima, Kazuhiko; Ushigusa, Takeshi; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Horai, Yoshiro; Nakajima, Hideki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Motomura, Masakatsu; Kawakami, Atsushi

    2015-04-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication in SLE. Although the mechanism of NPSLE remains unclear, cytokines and chemokines are considered to be involved in their pathogenesis. Here we used Bio-Plex Pro assays to examine 27 types of cytokines and chemokines in the cerebrospinal fluid (CSF) of 32 NPSLE patients. We used the CSF of 20 patients with multiple sclerosis (MS) and 22 patients with neuromyelitis optica (NMO) as a disease control group. Fourteen of 27 cytokines/chemokines were significantly higher in the NPSLE patients compared to the MS/NMO patients. We could identify six "minimum predictive markers" by using a weighted-voting algorithm that could distinguish NPSLE from MS and NMO: interleukin (IL)-17, IL-2, interferon (IFN)-γ, IL-5, basic fibroblast growth factor (FGF)-basic and IL-15. The determination of various types of CSF cytokine profiles may contribute to the diagnosis of NPSLE and may help elucidate the mechanisms underlying this disease.

  10. Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease.

    PubMed

    Johansson, Per; Almqvist, Erik G; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Svensson, Johan

    2015-11-16

    The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0.05 and P<0.01, respectively). Patients with other dementia or SMCI had lower CSF orexin A level than AD patients (both P<0.05) and marginally lower level than healthy controls (both P=0.05). CSF neurotensin level was similar in all groups. In the total study population (n=80), CSF substance P level correlated positively with CSF levels of T-tau and P-tau, and in AD patients (n=32), CSF substance P level correlated positively with CSF Aβ1-42 level. In conclusion, CSF substance P level was elevated in AD patients and correlated with CSF Aβ1-42 level, a well established marker of senile plaque pathology. The role of low CSF orexin A level in other dementias or SMCI needs to be explored in further studies.

  11. Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts.

    PubMed

    Butterworth, J; Gregory, C R; Aronson, L R

    1997-12-01

    Numerous studies suggest that modifications in concentrations of both excitatory and inhibitory amino acids are implicated in the pathophysiology of portal-systemic encephalopathy (PSE), a neuropsychiatric disorder associated with chronic liver disease in humans. In this study, amino acid levels were measured by High Performance Liquid Chromatography (HPLC) in Cerebrospinal Fluid (CSF) of 10 dogs (age range: 3 mo.- 3 yr 4 mo.) exhibiting a congenital portal-systemic shunt, either intra or extra-hepatic, and 8 age-matched control dogs who showed no signs of hepatic or neurologic disorders. Dogs with congenital shunts manifested signs of encephalopathy such as disorientation, head pressing, vocalization, depression, seizures and coma. CSF from dogs with congenital shunts contained significantly increased amounts of glutamate (2 to 3-fold increase, p<0.01), glutamine (6-fold increase, p<0.05) and aromatic amino acids (phenylalanine, tyrosine and tryptophan) compared to CSF of control dogs. Concentrations of GABA and branched chain amino acids (valine, leucine, isoleucine) were within normal limits. Modifications of brain glutamate (an excitatory amino acid) as well as tryptophan (the precursor of serotonin) could contribute to the neurological syndrome characteristic of congenital PSE in dogs.

  12. Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis

    PubMed Central

    Rodríguez-Martín, E; Picón, C; Costa-Frossard, L; Alenda, R; Sainz de la Maza, S; Roldán, E; Espiño, M; Villar, L M; Álvarez-Cermeño, J C

    2015-01-01

    Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56bright/CD56dim) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56bright and NK T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease. PMID:25565222

  13. Effect of endoscopic third ventriculostomy on cerebrospinal fluid pressure in the cerebral ventricles.

    PubMed

    Farnoush, Azadeh; Tan, Kristy; Juge, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2016-01-01

    We aimed to show how endoscopic third ventriculostomy (ETV) treatment may affect cerebrospinal fluid (CSF) flow dynamics in hydrocephalus, with and without aqueductal stenosis. Hydrocephalus is a neurological disorder which is characterized by enlarged brain ventricles. The periodic motion of CSF flow as a function of the cardiac cycle was prescribed as the inlet boundary condition at the foramen of Monro, and ETV was modeled as a 5mm diameter hole in the anterior wall of the third ventricle. The results show that ETV reduces the pressure in the ventricles by nine-fold in the model with aqueductal stenosis, and three-fold in the model without aqueductal stenosis. More importantly, ETV changes the temporal characteristics of the CSF pressure waveform in the model without aqueductal stenosis, such that there is higher pressure in the ventricle during diastole. This study suggests that changes in the temporal characteristics of the CSF pressure waveform in the ventricles may be the reason why ETV treatment is not effective for hydrocephalus without aqueductal stenosis.

  14. Cerebrospinal fluid lactate dehydrogenase isoenzymes in children with bacterial and aseptic meningitis.

    PubMed

    Nussinovitch, Moshe; Finkelstein, Yaron; Elishkevitz, Keren Politi; Volovitz, Benjamin; Harel, Daniella; Klinger, Gil; Razon, Yaron; Nussinovitch, Udi; Nussinovitch, Naomi

    2009-10-01

    Differentiation of bacterial from aseptic meningitis may be difficult. Our aim was to determine the pattern of distribution of lactate dehydrogenase (LDH) isoenzymes in the cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis. One hundred and fifty-seven patients with suspected meningitis were enrolled in the study. They were divided into 3 groups according to the culture- or bacterial antigen assay-proven diagnosis and CSF findings: bacterial meningitis (n = 31), aseptic meningitis (n = 65), and non-meningitis (n = 61). Total LDH level and percentages of LDH isoenzymes in the CSF were measured in each patient. Each group showed a distinct LDH isoenzyme distribution pattern, with a statistically significant difference among the groups in the percentages of the various isoenzymes. Compared with the non-meningitis group, total LDH activity in the CSF was high in the aseptic meningitis group (49.82+/-35.59 U/L, P < 0.001) and exaggerated in the bacterial meningitis group (944.53+/-112.3 U/L, P < 0.001). Low LDH-2 levels were unique to bacterial meningitis (P < 0.01), whereas high LDH-3 levels were characteristic of aseptic meningitis (P < 0.05). Both groups had low levels of LDH-1 and high levels of LDH-4 and LDH-5. In conclusion, the LDH isoenzyme pattern may be of clinical diagnostic value in meningitis, particularly when culture results are pending.

  15. Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite.

    PubMed

    Xing, Dan; Wu, Yuehong; Li, Guangling; Song, Siyuan; Liu, Yuepeng; Liu, He; Wang, Xing; Fei, Yan; Zhang, Chao; Li, Ying; Zhang, Licai

    2015-08-01

    The brainstem plays an important role in controlling sodium and water homeostasis. It is a major regulatory site for autonomic and motor functions. Moreover, it integrates cerebrospinal fluid (CSF) signals with neuronal and hormonal signals. Evidence suggests that the CSF-contacting nucleus (CSF-CN) transmits and integrates CSF signals, but, the definitive role of CSF-CN in sodium homeostasis is poorly understood. In this study, we used c-Fos as a marker of neuronal activity and causing colocalization of Nax channel and 5-HT. This proved that CSF-CN played a role in sensing the increase of CSF sodium level. Then, we determined the role of the CSF-contacting nucleus in increasing the sodium appetite of rats. So, we performed targeted lesion of the CSF-contacting nucleus in the brainstem using the cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. The lesion of the CSF-CN showed decreased and degenerative neurons, while sodium appetite have increased and Fos immunocytochemistry detected neuronal activity in the lateral parabrachial nucleus (LPBN), but not in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT). These results indicate that the CSF-CN plays an important role in sensing CSF sodium level and satiating sodium appetite by influencing the LPBN but not SFO and OVLT. The Nax channel and 5-HT might be the molecular mechanisms through which contribute to sodium homeostasis.

  16. Intraventricular migration of an isolated fourth ventricular cysticercus following cerebrospinal fluid shunting

    PubMed Central

    Khalid, Saifullah; Obaid, Amber; Sharma, Raman M.; Mahmood, Asad; Narayanasamy, Sabarish

    2016-01-01

    Background: Isolated intraventricular neurocysticercosis (NCC) is less frequently seen and can be missed on plain magnetic resonance imaging (MRI). Three-dimensional constructive interference in steady state (CISS) sequence is an extremely helpful sequence in identifying the lesion but is rarely used routinely. Case Description: Here, we report a case of young male adult who presented with diminution of vision and headache. MRI of the brain revealed hydrocephalus, and on using CISS sequence only, the lesion could be identified in the fourth ventricle. He was treated with medical management, and ventriculoperitoneal shunting of cerebrospinal fluid was done to relieve the hydrocephalus. It resulted in immediate relief with aggravation of headache few days later. Repeat MRI revealed intraventricular migration into the left foramen of monro leading to left lateral ventricle dilatation necessitating endoscopic removal of the lesion. Conclusion: CISS sequence is definitely the sequence of choice in identifying intraventricular NCC. Ventriculoperitoneal shunting can result in the intraventricular migration of the cyst due to sudden decompression necessitating repeat surgery. Endoscopic removal of NCC has a high success rate with limited complications. PMID:28031989

  17. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

    SciTech Connect

    Price, Richard W.; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E.; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena S.; Smith, Richard D.; Jacobs, Jon M.; Brown, Joseph N.; Gisslen, Magnus

    2013-12-13

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previouslydefined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  18. The comparison of three methods of drawing cerebrospinal fluid in rabbit.

    PubMed

    Li, Yan; Zhang, Bo; Wen, Wei; Liu, Shuang; Hao, Di; Liu, Ming; Kuang, Hai-Xue; Huang, Shu-Ming

    2012-08-15

    Component analysis of cerebrospinal fluid (CSF) is frequently required to probe the cause of disease, pathologic mechanisms and effective drugs in the experimental study of central nervous system. An ideal way of drawing CFS is very important for the successful analysis. However, pros and cons of types of CSF drawing have never been analyzed and compared. The purpose of this study was to choose an ideal method of obtaining CSF in rabbits by comparing the three usual ones: skull drilling, lumbar puncture and atlanto-occipital membrane puncture. In the study, the rabbits were randomly divided into three groups: skull drilling group, lumbar puncture group and atlanto-occipital membrane puncture group, and our modified puncture needles were used. The rates of success, operating time and repeatability, etc. of the three methods were compared. The results suggest that the atlanto-occipital membrane puncture method is the best. The method was the simplest, fastest, and most repeatable of the three, furthermore, with this method, the most CSF was drawn and achieved the highest success rate.

  19. Dural Defect Repair in Translabyrinthine Acoustic Neuroma Surgery and Its Implications in Cerebrospinal Fluid Leak Occurrence

    PubMed Central

    Netto, Aloysio Augusto Tahan de Campos; Colafêmina, José Fernando; Centeno, Ricardo Silva

    2012-01-01

    Cerebrospinal fluid (CSF) leak is a complication that may occur after translabyrinthine (translab) acoustic neuroma (AN) removal. The aim of this study is to verify the incidence of CSF leak using two techniques for dural defect closure in translab AN surgery and present a new technique for dural repair. A retrospective study was held, reviewing charts of 34 patients in a tertiary neurotologic referral center. Out of these 34 patients that underwent translab AN excision in a 1-year period, 18 had their dural defect repaired using only abdominal fat graft and 16 using synthetic dura substitute (SDS) plus abdominal fat tissue. One patient (5.5%) in the first group had CSF leak and 1 (6.2%) in the second group had CSF leak postoperatively. Our data suggest that there are no significant differences in CSF leak rates using both techniques, although studies in a larger series must be undertaken to conclude it. We believe that the development of some points in the new technique for dural repair can achieve better results and reduce the CSF leak incidence in the translabyrinthine acoustic neuroma surgery in the near future. PMID:24083124

  20. Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis.

    PubMed

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

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients.

  1. Simultaneous Determination of All Forms of Biopterin and Neopterin in Cerebrospinal Fluid

    PubMed Central

    2014-01-01

    In humans, genetic defects of the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor in hydroxylation reactions, are associated with severe neurological disorders. The diagnosis of these conditions relies on the determination of BH4, dihydrobiopterin (BH2), and dihydroneopterin (NH2) in cerebrospinal fluid (CSF). As MS/MS is less sensitive than fluorescence detection (FD) for this purpose, the most widely used method since 1980 involves two HPLC runs including two differential off-line chemical oxidation procedures aiming to transform the reduced pterins into their fully oxidized fluorescent counterparts, biopterin (B) and neopterin (N). However, this tedious and time-consuming two-step indirect method underestimates BH4, BH2, and NH2 concentrations. Direct quantification of BH4 is essential for studying its metabolism and for monitoring the efficacy of BH4 supplementation in patients with genetic defects. Here we describe a single step method to simultaneously measure BH4, BH2, B, NH2, and N in CSF by HPLC coupled to FD after postcolumn coulometric oxidation. All target pterins were quantified in CSF with a small volume (100 μL), and a single filtration step for sample preparation and analysis. As compared to the most widely used method in more than 100 CSF samples, this new assay is the easiest route for accurately determining in a single run BH4, BH2, and NH2 in CSF in deficit situations as well as for monitoring the efficacy of the treatment. PMID:24650440

  2. Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier

    SciTech Connect

    Zlokovic, B.V.; Segal, M.B.; Davson, H.; Jankov, R.M.

    1988-05-01

    Unidirectional flux of /sup 125/I-labeled DSIP at the blood-tissue interface of the blood-cerebrospinal fluid (CSF) barrier was studied in the perfused in situ choroid plexuses of the lateral ventricles of the sheep. Arterio-venous loss of /sup 125/I-radioactivity suggested a low-to-moderate permeability of the choroid epithelium to the intact peptide from the blood side. A saturable mechanism with Michaelis-Menten type kinetics with high affinity and very low capacity (approximate values: Kt = 5.0 +/- 0.4 nM; Vmax = 272 +/- 10 fmol.min-1) was demonstrated at the blood-tissue interface of the choroid plexus. The clearance of DSIP from the ventricles during ventriculo-cisternal perfusion in the rabbit indicated no significant flux of the intact peptide out of the CSF. The results suggest that DSIP crosses the blood-CSF barrier, while the system lacks the specific mechanisms for removal from the CSF found with most, if not all, amino acids and several peptides.

  3. A comparative study on neurochemistry of cerebrospinal fluid in advanced Parkinson's disease.

    PubMed

    Liu, H; Iacono, R P; Schoonenberg, T; Kuniyoshi, S; Buchholz, J

    1999-02-01

    This study addresses two issues: (1) the comparative neurochemistry of classic tremor type of Parkinson's disease or PD-A and akinetic type of Parkinson's disease or PD-B; and (2) the neurochemistry of levodopa failure syndrome (LDFS). Cerebrospinal fluid from the lateral ventricle was collected from 50 patients with idiopathic Parkinson's disease of PD-A and PD-B. Levels of monoamine neurotransmitters and metabolites were determined using high performance liquid chromatography. We have found that (1) 5-hydroxylindoleacetic acid (5-HIAA) level is significantly lower in PD-B than in PD-A; (2) 5-HIAA level is inversely associated with score of part one of United Parkinson's Disease Rating Score (UPDRS); (3) 5-HIAA level is inversely associated with score of part four of UPDRS; (4) 3-O-methyldopa (3-OMD) level is positively associated with levodopa failure syndrome (LDFS) assessed by part four of UPDRS and inversely associates with 5-HIAA. From these data, it can be inferred that serotonergic activity is decreased in PD-B to a greater extent than in PD-A and that decreased serotonergic activity plays a role in LDFS.

  4. Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis.

    PubMed

    Rodríguez-Martín, E; Picón, C; Costa-Frossard, L; Alenda, R; Sainz de la Maza, S; Roldán, E; Espiño, M; Villar, L M; Álvarez-Cermeño, J C

    2015-05-01

    Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56(bright) /CD56(dim) ) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56(bright) and NK T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease.

  5. Sellar Reconstruction and Rates of Delayed Cerebrospinal Fluid Leak after Endoscopic Pituitary Surgery

    PubMed Central

    Sanders-Taylor, Chris; Anaizi, Amjad; Kosty, Jennifer; Zimmer, Lee A.; Theodosopoulos, Phillip V.

    2015-01-01

    Objectives Delayed cerebrospinal fluid (CSF) leaks are a complication in transsphenoidal surgery, potentially causing morbidity and longer hospital stays. Sella reconstruction can limit this complication, but is it necessary in all patients? Design Retrospective review. Setting Single-surgeon team (2005–2012) addresses this trend toward graded reconstruction. Participants A total of 264 consecutive patients with pituitary adenomas underwent endoscopic transsphenoidal resections. Sellar defects sizable to accommodate a fat graft were reconstructed. Main outcomes Delayed CSF leak and autograft harvesting. Results Overall, 235 (89%) had reconstruction with autograft (abdominal fat, septal bone/cartilage) and biological glue. Delayed CSF leak was 1.9%: 1.7%, and 3.4% for reconstructed and nonreconstructed sellar defects, respectively (p = 0.44). Complications included one reoperation for leak, two developed meningitis, and autograft harvesting resulted in abdominal hematoma in 0.9% and wound infection in 0.4%. Conclusion In our patients, delayed CSF leaks likely resulted from missed intraoperative CSF leaks or postoperative changes. Universal sellar reconstruction can preemptively treat missed leaks and provide a barrier for postoperative changes. When delayed CSF leaks occurred, sellar reconstruction often allowed for conservative treatment (i.e., lumbar drain) without repeat surgery. We found universal reconstruction provides a low risk of delayed CSF leak with minimal complications. PMID:26225317

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

    PubMed Central

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

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients. PMID:25892962

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

    PubMed Central

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

    2015-01-01

    A flow sensor has been fabricated and tested that is capable of measuring the slow flow characteristic of the cerebrospinal fluid in the range from less than 4 mL/h to above 100 mL/h. This sensor is suitable for long-term implantation because it uses a wireless external spectrometer to measure passive subcutaneous components. The sensors are pressure-sensitive capacitors, in the range of 5 pF with an air gap at atmospheric pressure. Each capacitor is in series with an inductor to provide a resonant frequency that varies with flow rate. At constant flow, the system is steady with drift <0.3 mL/h over a month. At variable flow rate, V̇, the resonant frequency, f0, which is in the 200–400 MHz range, follows a second order polynomial with respect to V̇. For this sensor system the uncertainty in measuring f0 is 30 kHz which corresponds to a sensitivity in measuring flow of ΔV̇= 0.6 mL/hr. Pressures up to 20 cm H2O relative to ambient pressure were also measured. An implantable twin capacitor system is proposed that can measure flow, which is fully compensated for all hydrostatic pressures. For twin capacitors, other sources of systematic variation within clinical range, such as temperature and ambient pressure, are smaller than our sensitivity and we delineate a calibration method that should maintain clinically useful accuracy over long times. PMID:26543321

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

    PubMed

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

    2016-05-01

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

  9. Microtubule proteins and their post-translational forms in the cerebrospinal fluid of patients with paraparesis associated with HTLV-I infection and in SH-SY5Y cells: an in vitro model of HTLV-I-induced disease.

    PubMed

    Maldonado, Horacio; Ortiz-Riaño, Emilio; Krause, Bernardo; Barriga, Andrés; Medina, Fernando; Pando, M Elsa; Alberti, Carolina; Kettlun, Ana M; Collados, Lucía; García, Lorena; Cartier, Luis; Valenzuela, M Antonieta

    2008-01-01

    HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by axonal degeneration of the corticospinal tracts. The specific requirements for transport of proteins and organelles to the distal part of the long axon are crucial in the corticospinal tracts. Microtubule dysfunction could be involved in this disease, configuring an axonal transport disease. We measured tubulin and its post-translational modified forms (acetylated and tyrosinated) in CSF of patients and controls, as well as tau and its phosphorylated forms. There were no significant differences in the contents of tubulin and acetyl-tubulin between patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau levels were significantly reduced, while the ratio of pT181/total tau was higher in patients than in controls, this being completely different from what is reported in other neurodegenerative diseases. Phosphorylation at T181 was also confirmed by Mass Spectrometry analysis. Western Blotting with monospecific polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and pS422 did not show differences in phosphorylation in these residues between patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I infected cell line that secretes the viral Tax protein) we observed neurite retraction and an increase in tau phosphorylation at T181. A disruption of normal phosphorylation of tau protein in T181 could result in its dysfunction, contributing to axonal damage.

  10. Cross-sectional imaging of thoracic and abdominal complications of cerebrospinal fluid shunt catheters.

    PubMed

    Bolster, Ferdia; Fardanesh, Reza; Morgan, Tara; Katz, Douglas S; Daly, Barry

    2016-04-01

    This study aims to review the imaging findings of distal (thoracic and abdominal) complications related to ventriculo-peritoneal (VP), ventriculo-pleural (VPL), and ventriculo-atrial (VA) cerebrospinal fluid (CSF) shunt catheter placement. Institution review board-approved single-center study of patients with thoracic and abdominal CSF catheter-related complications on cross-sectional imaging examinations over a 14-year period was performed. Clinical presentation, patient demographics, prior medical history, and subsequent surgical treatment were recorded. The presence or absence of CSF catheter-related infection and/or acute hydrocephalus on cross-sectional imaging was also recorded. There were 81 distal CSF catheter-related complications identified on 47 thoracic or abdominal imaging examinations in 30 patients (age 5-80 years, mean 39.3 years), most often on CT (CT = 42, MRI = 1, US = 4). Complications included 38 intraperitoneal and 11 extraperitoneal fluid collections. Extraperitoneal collections included nine abdominal wall subcutaneous (SC) pseudocysts associated with shunt migration and obesity, an intrapleural pseudocyst, and a breast pseudocyst. There were also two large VPL-related pleural effusions, a fractured catheter in the SC tissues, and a large VA shunt thrombus within the right atrium. Ten patients (33.3 %) had culture-positive infection from CSF or shunt catheter samples. Ten patients (33.3 %) had features of temporally related acute or worsening hydrocephalus on neuroimaging. In four of these patients, the detection of thoracic and abdominal complications on CT preceded and predicted the findings of acute hydrocephalus on cranial imaging. Thoracic and abdominal complications of CSF shunts, as can be identified on CT, include shunt infection and/or obstruction, may be both multiple and recurrent, and may be predictive of concurrent acute intracranial problems.

  11. Factors in cerebrospinal fluid from goats that affect sleep and activity in rats*

    PubMed Central

    Fencl, V.; Koski, G.; Pappenheimer, J. R.

    1971-01-01

    1. Intraventricular infusion in the rat of 0·1 ml. cerebrospinal fluid (c.s.f.) from sleep-deprived goats increases the duration of sleep (measured by e.e.g.) and decreases locomotor activity (measured photo-electrically) for at least 6 hr subsequent to the infusion. Subarachnoid infusions are ineffective. 2. C.s.f. from control and sleep-deprived goats was fractionated by ultrafiltration through molecular sieves. The sleep-promoting Factor S is found in the low molecular weight fraction (mol. wt. < 500) of c.s.f. from sleep-deprived but not from control goats. 3. The concentration of Factor S in c.s.f. increases progressively during the first 48 hr of sleep deprivation. 4. The sleep promoting effects of Factor S cannot be duplicated by serotonin, 4-OH-butyrate, butyrolactone, GABA (γ-amino butyric acid), glutamic acid or 3′,5′-cyclic AMP when these substances are added to control fluids in concentrations up to 10 times greater than those found in normal c.s.f. 5. Intraventricular or subarchnoid infusion in the rat of 0·1 ml. proteinfree c.s.f. containing molecules in the mol. wt. range of 500-10,000 at 10-30 × normal concentration causes hyperactivity which persists for several days and nights following the infusion. The excitatory material, probably a peptide, is present in c.s.f. from both control and sleep-deprived goats. 6. The properties of Factor S suggest that it may play a role in the normal regulation of sleep and wakefulness. PMID:4327693

  12. Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport.

    PubMed

    Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

    2017-03-18

    The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins.

  13. Extracellular Biotransformation of β-Endorphin in Rat Striatum and Cerebrospinal Fluid

    PubMed Central

    Reed, Brian; Bidlack, Jean M.; Chait, Brian T.; Kreek, Mary Jeanne

    2009-01-01

    Numerous studies have investigated the behavioural effects of β-endorphin, both endogenous and exogenously applied. However, the potential for biotransformation of β-endorphin in the extracellular space of the brain has not been previously directly addressed in vivo. Utilising microinfusion/microdialysis and MALDI mass spectrometry, we investigated β-endorphin biotransformation in the striatum rats. We infused 1.0 nmol β-endorphin into the striatum of adult male Fischer rats and observed rapid cleavage resulting in β-endorphin 1-18, as well as several fragments resulting from further N-terminal degradation. In vitro studies with incubation of full-length β-endorphin, with and without protease inhibitors, in the incubation fluid of isolated striatal slices indicate β-endorphin is initially cleaved predominantly at the Phe18-Lys19, position, as well as at the Leu17-Phe18 position. Investigations of cerebrospinal fluid revealed similar enzymatic cleavage of β-endorphin. The observed pattern of cleavage sites (Phe18-Lys19 and Leu17-Phe18) is consistent with published in vitro studies of purified insulin-degrading enzyme cleavage of β-endorphin. The binding affinities of full-length β-endorphin, as well as previously identified β-endorphin fragments α-endorphin (β-endorphin 1-16) and γ-endorphin (β-endorphin 1-17), and the fragment identified in the current studies, β-endorphin 1-18, at heterologously expressed MOP, DOP, and KOP receptors (μ, δ, and κ-opioid receptors, respectively) were determined; the affinity of the truncation fragments is reduced at each of the receptors compared to the affinity of full length β-endorphin. PMID:18363801

  14. Chemokine biomarkers in central nervous system tissue and cerebrospinal fluid in the Theiler's virus model mirror those in multiple sclerosis.

    PubMed

    Pachner, Andrew R; Li, Libin; Gilli, Francesca

    2015-12-01

    Chemokines have increasingly been implicated in inflammatory and infectious disease of the central nervous system, both as biomarkers and as molecules important in pathogenesis. Multiple sclerosis is a disabling disease of unknown etiology, and recently chemokines have been identified as being upregulated molecules in the disease. We were interested in how the chemokine expression patterns in the central nervous system of a viral model of multiple sclerosis, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), compared to that in humans with multiple sclerosis. Cerebrospinal fluid and spinal cord tissue were analyzed for expression of a range of cytokines and chemokines. Three chemokines, CXCL10, CXCL9, and CCL5 were strongly and specifically upregulated in both the cerebrospinal fluid and spinal cord in chronic disease, a pattern identical to that in multiple sclerosis. These data, the first study of cytokines in central nervous system tissue and cerebrospinal fluid in TMEV-IDD, support the hypothesis that multiple sclerosis is caused by chronic infection with an as-yet unidentified pathogen, possibly a picornavirus.

  15. Effects of mild hypothermia therapy on the levels of glutathione in rabbit blood and cerebrospinal fluid after cardiopulmonary resuscitation

    PubMed Central

    Zhao, Hui; Chen, Yueliang

    2015-01-01

    Objective(s): The aim of this study was to investigate the effects of mild hypothermia therapy on oxidative stress injury of rabbit brain tissue after cardiopulmonary resuscitation (CPR). Materials and Methods: Rabbit models of cardiac arrest were established. After the restoration of spontaneous circulation, 50 rabbits were randomly divided into normothermia and hypothermia groups. The following five time points were selected: before CPR, immediately after CPR, 2 hr after CPR (hypothermia group reached the target temperature), 14 hr after CPR (hypothermia group before rewarming), and 24 hr after CPR (hypothermia group recovered to normal temperature). Glutathione (GSH) concentrations in both the blood and cerebrospinal fluid of the normothermia and hypothermia groups were measured. Results: At 2, 14, and 24 hr after CPR, the GSH concentrations in both the blood and cerebrospinal fluid were significantly higher in the hypothermia group than in the nomorthermia group. Conclusion: Mild hypothermia therapy may increase GSH concentrations in rabbit blood and cerebrospinal fluid after CPR as well as promote the recovery of cerebral function. PMID:25810895

  16. The body mass index (BMI) is significantly correlated with levels of cytokines and chemokines in cerebrospinal fluid.

    PubMed

    Larsson, Anders; Carlsson, Lena; Lind, Anne-Li; Gordh, Torsten; Bodolea, Constantin; Kamali-Moghaddam, Masood; Thulin, Måns

    2015-12-01

    Cytokines and chemokines regulate many functions in the body including the brain. The interactions between adipose tissue and the central nervous system (CNS) are important for the regulation of energy balance. CNS function is also influenced by age. The aim of the present study was to investigate the effects of body mass index (BMI) and age on cytokine and chemokine levels in cerebrospinal fluid. Cerebrospinal fluid samples (n=89) were collected from patients undergoing routine surgical procedures. The samples were analyzed using the multiplex proximity extension assay (PEA) in which 92 different cytokines are measured simultaneously using minute sample volume. We found no significant correlations between age and cytokine levels for any of the studied markers. In contrast, at a false discovery rate of 10%, 19 markers were significantly associated with BMI (in decreasing significance: FGF-5, ADA, Beta-NGF, CD40, IL-10RB, CCL19, TGF-alpha, SIRT2, TWEAK, SCF, CSF-1, 4E-BP1, DNER, LIF-R, STAMPB, CXCL10, CXCL6, VEGF-A and CX3CL1). This study reveals a clear effect of BMI on cytokine and chemokine levels in cerebrospinal fluid.

  17. Postoperative Low-Flow Cerebrospinal Fluid Leak of Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma--Wait and See, or Lumbar Drain?

    PubMed

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

    2015-06-01

    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.

  18. Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review)

    PubMed Central

    Agnati, Luigi F.; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

    2017-01-01

    In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico-physical parameters, oscillatory rhythms within their proper set-ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio-pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis. PMID:28204813

  19. Concentration of Donepezil in the Cerebrospinal Fluid of AD Patients: Evaluation of Dosage Sufficiency in Standard Treatment Strategy.

    PubMed

    Valis, Martin; Masopust, Jiri; Vysata, Oldrich; Hort, Jakub; Dolezal, Rafael; Tomek, Jiri; Misik, Jan; Kuca, Kamil; Karasova, Jana Zdarova

    2017-01-01

    Although some studies have described the pharmacokinetics and pharmacodynamics of donepezil in the peripheral compartment, studies focused on drug transport across the blood-brain barrier are still very rare. To our knowledge, the fluctuation in the cerebrospinal fluid concentration of donepezil after administration of the drug has not been described in the literature so far. We recruited 16 patients regularly taking a standard therapeutic dose of donepezil (10 mg per day). All patients (Caucasian race) were treated for at least three months with a stable dose of 10 mg per day prior to sample collection. Patients were divided into two groups depending on the time of plasma and cerebrospinal fluid sampling: 12 h (n = 9; 4 M/5F aged 78.68 ± 7.35 years) and 24 h (n = 7; 3 M/4F aged 77.14 ± 5.87 years) after donepezil administration. The cerebrospinal fluid sample was collected by standard lumbar puncture technique using a single-use traumatic needle. The samples were analysed on an Agilent 1260 Series liquid chromatograph comprising a degasser, a quaternary pump, a light-tight autosampler unit set, a thermostated column compartment, and a UV/VIS detector. Agilent ChemStation software, the statistical software Prism4, version 5.0 (GraphPad Software, USA), and IBM(®) SPSS(®) Statistics were used for the analysis of the results. The difference in plasma concentration of donepezil after 12 h (mean ± SEM; 39.99 ± 5.90 ng/ml) and after 24 h (29.38 ± 1.71 ng/ml) was nonsignificant. In contrast, the donepezil concentration in the cerebrospinal fluid was significantly higher in the 24-h interval (7.54 ± 0.55 ng/ml) compared with the 12-h interval (5.19 ± 0.83 ng/ml, which is ~70 % based on mean cerebrospinal fluid values). Based on these data, it is plausible to predict that donepezil might produce a stronger AChE inhibition in the brain at 24 h compared with 12 h following the administration. This information may help physicians

  20. Temporal Profile of Cerebrospinal Fluid, Plasma, and Brain Interleukin-6 After Normothermic Fluid-Percussion Brain Injury: Effect of Secondary Hypoxia

    PubMed Central

    Chatzipanteli, Katina; Vitarbo, Elizabeth; Alonso, Ofelia F.; Bramlett, Helen M.

    2012-01-01

    Interleukin-6 (IL-6) is a proinflammatory cytokine that may play multiple roles in the pathogenesis of traumatic brain injury (TBI). The present study determined time-dependent changes in IL-6 concentrations in vulnerable brain regions, cerebrospinal fluid (CSF) samples, and plasma after normothermic TBI. Because secondary insults are common in head injured patients, we also assessed the consequences of a post-traumatic secondary hypoxic insult on this pleiotropic cytokine. Male Sprague-Dawley rats were intubated, anesthetized, and underwent a moderate parasagittal fluid-percussion brain injury (1.8–2.1 atm, 37°C) followed by either 30 minutes of normoxic or hypoxic (pO2=30–40 mmHg) gas levels. Rats were sacrificed 3, 6, or 24 hours after TBI or sham-operated procedures. Brain samples, including the ipsilateral cerebral cortex and hippocampus were dissected and analyzed. Plasma and CSF samples were collected at similar times and stored at −80°C until analysis. IL-6 levels were significantly increased (p<0.05) at 3, 6, and 24 hours in the cerebral cortex and at 6 hours in the hippocampus after TBI. IL-6 levels in the TBI normoxic group for both structures returned to control levels by 24 hours. Plasma levels of IL-6 were elevated at all time points, while CSF levels were high at 3 and 6 hours, but normalized by 24 hours. Post-traumatic hypoxia led to significantly elevated (p<0.05) IL-6 protein levels in the cerebral cortex at 24 hours compared to sham-operated controls. These findings demonstrate that moderate TBI leads to an early increase in IL-6 brain, plasma, and CSF protein levels. Secondary post-traumatic hypoxia, a common secondary injury mechanism, led to prolonged elevations in plasma IL-6 levels that may participate in the pathophysiology of this complicated TBI model. PMID:23667780