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Sample records for cerebrospinal fluid csf

  1. Characterization of lipoproteins in human and canine cerebrospinal fluid (CSF)

    SciTech Connect

    Pitas, R.E.; Weisgraber, K.H.; Boyles, J.K.; Lee, S.; Mahley, R.W.

    1986-03-01

    Previously the authors demonstrated that rat brain astrocytes in vitro synthesize and secrete apo-E and possess apo-B,E(LDL) receptors. The apo-E secreted by astrocytes and apo-E in rat brain extracts differed from serum apo-E in two respects. Brain apo-E had a higher apparent molecular weight and a higher percentage of more acidic isoforms. To characterize further the apo-E within the central nervous system, apo-E in human and canine CSF was investigated. Compared to plasma apo-E, CSF apo-E had a higher apparent M/sub r/ and a higher percentage of acidic isoforms which were sialylated, as shown by neuraminidase digestion. The apo-E in human CSF was approx.5-10% of the plasma level. In CSF 60-80% of the apo-E was in lipoproteins with d = 1.09-1.15. The remainder of the apo-E was in the d > 1.21 fraction. Human CSF lipoproteins were primarily spherical (110-190 A) while canine CSF lipoproteins were a mixture of discs (205 x 65 A) while canine CSF lipoproteins were a mixture of discs (205 x 65 A) and spheres (100-150 A). The CSF also contained apo-AI in the d = 1.09-1.15 g/ml fraction. Human CSF lipoproteins containing both apo-E and apo-AI were isolated on an anti-apo-E affinity column, suggesting that apo-E and AI occurred in the same particles. The CSF apo-E-containing lipoproteins competed for binding of /sup 125/I-LDL to the apo-B,E(LDL) receptor. There was no detectable apo-B in CSF. These data suggest that CSF lipoproteins might transport lipid and regulate lipid homeostasis within the brain.

  2. Pharmacologic manipulation of the flushing action of cerebrospinal fluid. Effect on CSF diatrizoate levels.

    PubMed

    Harnish, P P; Samuel, K

    1988-12-01

    The continual production and absorption of cerebrospinal fluid (CSF) provides for the dilution and removal of potentially toxic substances from the central nervous system (CNS). This study quantified changes in the CSF concentration of diatrizoate following pretreatment with various drugs that alter CSF production. Adult rats, pretreated with one of ten drugs or normal saline (control) and anesthetized, received sodium diatrizoate (2 mL/kg, IV). Blood and CSF were sampled 2 hours later, and the diatrizoate concentrations were measured. Serum diatrizoate levels in the control group averaged 144.3 micrograms/mL. There were no significant differences in serum levels between control and pretreated groups. The CSF diatrizoate concentration in the control group averaged 10.8 micrograms/mL. Pretreatment with acetazolamide, ritodrine, or probenecid resulted in a significant increase in the CSF concentration, to 24.7 micrograms/mL or 228% of control in the case of acetazolamide. Pretreatment with salicylate, carbachol, or aminophylline resulted in significantly lower CSF diatrizoate levels than control; 3.2 micrograms/mL (30% of control) for carbachol. Digoxin, furosemide, dibutyryl cAMP, or dexamethasone pretreatments had no significant effect on CSF diatrizoate concentrations. Thus, a wide range of drugs may significantly alter the concentration of diatrizoate in the CNS. Drug-induced changes in the rate of CSF production may be responsible for this action. PMID:2849595

  3. Cerebrospinal Fluid Biomarkers of Simian Immunodeficiency Virus Encephalitis : CSF Biomarkers of SIV Encephalitis.

    PubMed

    Bissel, Stephanie J; Kofler, Julia; Nyaundi, Julia; Murphey-Corb, Michael; Wisniewski, Stephen R; Wiley, Clayton A

    2016-06-01

    Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease. PMID:27059917

  4. Cerebrospinal fluid.

    PubMed

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

    2001-08-01

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

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

    PubMed

    Simon, Matthew J; Iliff, Jeffrey J

    2016-03-01

    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. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. PMID:26499397

  6. 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.

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

    PubMed Central

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

    2008-01-01

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

  8. Cerebrospinal Fluid (CSF) Neuronal Biomarkers across the Spectrum of HIV Infection: Hierarchy of Injury and Detection

    PubMed Central

    Peterson, Julia; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Shacklett, Barbara L.; Hagberg, Lars; Yiannoutsos, Constantin T.; Spudich, Serena S.; Price, Richard W.

    2014-01-01

    The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary infection; four groups of chronic HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200–349, 50–199, and <50 cells/µL; HAD; treatment-induced viral suppression; and ‘elite’ controllers. Samples from 20 HIV-uninfected controls were also examined. The neuronal biomarkers included neurofilament light chain protein (NFL), total and phosphorylated tau (t-tau, p-tau), soluble amyloid precursor proteins alpha and beta (sAPPα, sAPPβ) and amyloid beta (Aβ) fragments 1–42, 1–40 and 1–38. Comparison of the biomarker changes showed a hierarchy of sensitivity in detection and suggested evolving mechanisms with progressive injury. NFL was the most sensitive neuronal biomarker. Its CSF concentration exceeded age-adjusted norms in all HAD patients, 75% of NA CD4<50, 40% of NA CD4 50–199, and 42% of primary infection, indicating common neuronal injury with untreated systemic HIV disease progression as well as transiently during early infection. By contrast, only 75% of HAD subjects had abnormal CSF t-tau levels, and there were no significant differences in t-tau levels among the remaining groups. sAPPα and β were also abnormal (decreased) in HAD, showed less marked change than NFL with CD4 decline in the absence of HAD, and were not decreased in PHI. The CSF Aβ peptides and p-tau concentrations did not differ among the groups, distinguishing the HIV CNS injury profile from Alzheimer's disease. These CSF biomarkers can serve as useful tools in selected research and clinical settings for patient classification, pathogenetic

  9. microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF).

    PubMed

    Alexandrov, Peter N; Dua, Prerna; Hill, James M; Bhattacharjee, Surjyadipta; Zhao, Yuhai; Lukiw, Walter J

    2012-01-01

    Human cerebrospinal fluid (CSF), produced by the choroid plexus and secreted into the brain ventricles and subarachnoid space, plays critical roles in intra-cerebral transport and the biophysical and immune protection of the brain. CSF composition provides valuable insight into soluble pathogenic bio-markers that may be diagnostic for brain disease. In these experiments we analyzed amyloid beta (Aβ) peptide and micro RNA (miRNA) abundance in CSF and in short post-mortem interval (PMI <2.1 hr) brain tissue-derived extracellular fluid (ECF) from Alzheimer's disease (AD) and age-matched control neocortex. There was a trend for decreased abundance of Aβ42 in the CSF and ECF in AD but it did not reach statistical significance (mean age ~72 yr; N=12; p~0.06, ANOVA). The most abundant nucleic acids in AD CSF and ECF were miRNAs, and their speciation and inducibility were studied further. Fluorescent miRNA-array-based analysis indicated significant increases in miRNA-9, miRNA-125b, miRNA-146a, miRNA-155 in AD CSF and ECF (N=12; p<0.01, ANOVA). Primary human neuronal-glial (HNG) cell co-cultures stressed with AD-derived ECF also displayed an up-regulation of these miRNAs, an effect that was quenched using the anti-NF-кB agents caffeic acid phenethyl ester (CAPE) or 1-fluoro-2-[2-(4-methoxy-phenyl)-ethenyl]-benzene (CAY10512). Increases in miRNAs were confirmed independently using a highly sensitive LED-Northern dot-blot assay. Several of these NF-кB-sensitive miRNAs are known to be up-regulated in AD brain, and associate with the progressive spreading of inflammatory neurodegeneration. The results indicate that miRNA-9, miRNA-125b, miRNA-146a and miRNA-155 are CSF- and ECF-abundant, NF-кB-sensitive pro-inflammatory miRNAs, and their enrichment in circulating CSF and ECF suggest that they may be involved in the modulation or proliferation of miRNA-triggered pathogenic signaling throughout the brain and central nervous system (CNS). PMID:23301201

  10. Laparoscopic repositioning of a ventriculo-peritoneal catheter tip for a sterile abdominal cerebrospinal fluid (CSF) pseudocyst.

    PubMed

    Oh, A; Wildbrett, P; Golub, R; Yu, L M; Goodrich, J; Lee, T

    2001-05-01

    Abdominal cerebrospinal fluid (CSF) pseudocyst is an uncommon but well-described complication that is reported to occur in <1% of ventriculo-peritoneal (VP) shunts. Management options for pseudocysts include various types of shunt revisions, which recently have been conducted laparoscopically. We report the case of an 11-year-old girl in whom a sterile abdominal CSF pseudocyst was successfully fenestrated and the VP catheter repositioned using laparoscopy. This technique in the setting of a noninfected pseudocyst has proven to be safe, with results comparable to the conventional open technique. However, the long-term success rate is still unknown. PMID:11353974

  11. [Understanding of cerebrospinal fluid hydrodynamics in idiopathic hydrocephalus (A) Visualization of CSF bulk flow with MRI time-spatial labeling pulse method (time-SLIP)].

    PubMed

    Yamada, Shinya; Goto, Tadateru

    2010-11-01

    Cerebrospinal fluids (CSF) hydrodynamics in normal and hydrocephalic brain was observed noninvasively using a time-spatial labeling inversion pulse (SLIP) technique. A time-SLIP technique applied label to CSF in the region of interest so that CSF became internal CSF tracer. CSF hydrodynamics even in normal brain appeared to be much different from it was imagine from conventional CSF physiology text books. Various amplitudes of pulsatile CSF flow were observed in the different regions of the brain. CSF hydrodynamics altered when hydrocephalus was developed. A time-SLIP CSF flow imaging is helpful to understand CSF hydrodynamics in the normal physiological and hydrocephalic brain. It may be useful to distinguish the hydrocephalus brain from the senile atrophic brain. PMID:21921529

  12. Cerebrospinal Fluid (CSF) CD8+ T-Cells That Express Interferon-Gamma Contribute to HIV Associated Neurocognitive Disorders (HAND)

    PubMed Central

    Schrier, Rachel D.; Hong, Suzi; Crescini, Melanie; Ellis, Ronald; Pérez-Santiago, Josué; Spina, Celsa; Letendre, Scott

    2015-01-01

    Background HIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis. Methods To investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART. Results Data were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFNγ expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFNγ and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/μl and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFNγ expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF. Conclusions Presence of IFNγ expressing CD8+ T

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  15. Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count.

    PubMed

    Yushchenko, M; Weber, F; Mäder, M; Schöll, U; Maliszewska, M; Tumani, H; Felgenhauer, K; Beuche, W

    2000-10-01

    Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in 111 paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood-brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per microl. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count (r=0.755; P<0.0001), but not with CSF/serum albumin ratio (Q(Alb)) (r=0.212; P=0.057), a measure for BBB impairment. Moreover, the CSF/serum MMP-9 ratio (Q(MMP-9)) did not correlate with Q(Alb)(r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells (r(2)=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed. PMID:11024556

  16. Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis

    PubMed Central

    2013-01-01

    Objective Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia. Methods This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed. Results The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n = 7, 71%–100%), other Klebsiella species (n = 7, 28%–80%), and Staphylococcus (n = 36, 25%–40%). Conclusions The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high

  17. Development of a permeability-limited model of the human brain and cerebrospinal fluid (CSF) to integrate known physiological and biological knowledge: Estimating time varying CSF drug concentrations and their variability using in vitro data.

    PubMed

    Gaohua, Lu; Neuhoff, Sibylle; Johnson, Trevor N; Rostami-Hodjegan, Amin; Jamei, Masoud

    2016-06-01

    A 4-compartment permeability-limited brain (4Brain) model consisting of brain blood, brain mass, cranial and spinal cerebrospinal fluid (CSF) compartments has been developed and incorporated into a whole body physiologically-based pharmacokinetic (PBPK) model within the Simcyp Simulator. The model assumptions, structure, governing equations and system parameters are described. The model in particular considers the anatomy and physiology of the brain and CSF, including CSF secretion, circulation and absorption, as well as the function of various efflux and uptake transporters existing on the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB), together with the known parameter variability. The model performance was verified using in vitro data and clinical observations for paracetamol and phenytoin. The simulated paracetamol spinal CSF concentration is comparable with clinical lumbar CSF data for both intravenous and oral doses. Phenytoin CSF concentration-time profiles in epileptic patients were simulated after accounting for disease-induced over-expression of efflux transporters within the BBB. Various 'what-if' scenarios, involving variation of specific drug and system parameters of the model, demonstrated that the 4Brain model is able to simulate the possible impact of transporter-mediated drug-drug interactions, the lumbar puncture process and the age-dependent change in the CSF turnover rate on the local PK within the brain. PMID:27236639

  18. [Cerebrospinal fluid syndrome in neuroschistosomiasis].

    PubMed

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

    1985-12-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Cerebrospinal fluid flow in adults.

    PubMed

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

    2016-01-01

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

  1. Cerebrospinal fluid stasis and its clinical significance.

    PubMed

    Whedon, James M; Glassey, Donald

    2009-01-01

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

  2. 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.

  3. 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

  4. [Alterations of cerebrospinal fluid pressure in experimental communicating hydrocephalus. Response of CSF-pressure to increased CO2-tension (author's transl)].

    PubMed

    Strecker, E P; Schmidt-Hieber, M; Kauffmann, G; Berg, G; Mathias, K

    1977-07-15

    The response of cerebrospinal fluid pressure to increased arterial carbon dioxide tension was examined in 5 control dogs and 7 dogs with experimental communicating hydrocephalus. The cerebrospinal fluid pressure in control animals only rose to 35 mm Hg after elevation of the arterial CO2 tension. In dogs with experimental communicating hydrocephalus, however, a significant rise of intracranial pressure to 60 mm Hg can be demonstrated. This is accompained by a marked simultaneous decrease of cerebral perfusion pressure in hydrocephalic animals. Progression of communicating hydrocephalus can be explained as damage to the cerebral tissue by increased intracranial pressure waves and by ischemia due to low cerebral perfusion pressure. PMID:20069

  5. Cerebrospinal fluid monoamine metabolites and suicide.

    PubMed

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

    2009-01-01

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

  6. Endonasal Endoscopic Closure of Cerebrospinal Fluid Rhinorrhea

    PubMed Central

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

    2001-01-01

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

  7. 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)

  8. Cerebrospinal fluid analysis after unprovoked first seizure

    PubMed Central

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

    2016-01-01

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

  9. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    PubMed

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

    2015-06-01

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

  10. Proteome analysis of chick embryonic cerebrospinal fluid.

    PubMed

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

    2006-01-01

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

  11. Evaluation of the Production and Absorption of Cerebrospinal Fluid

    PubMed Central

    MIYAJIMA, Masakazu; ARAI, Hajime

    2015-01-01

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

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

    PubMed

    Miyajima, Masakazu; Arai, Hajime

    2015-01-01

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

  13. [Cerebrospinal fluid diagnostics for neuroinfectious diseases].

    PubMed

    Spreer, A; Nau, R

    2015-02-01

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

  14. Malignancy markers in the cerebrospinal fluid.

    PubMed

    Koskiniemi, M

    1988-10-01

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

  15. Cerebrospinal Fluid Flow Studies and Recent Advancements.

    PubMed

    Kelly, Erin J; Yamada, Shinya

    2016-04-01

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

  16. 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

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

    PubMed

    Perlman, S; Carr, S A

    1984-07-01

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

  18. Development and validation of a sample stabilization strategy and a UPLC-MS/MS method for the simultaneous quantitation of acetylcholine (ACh), histamine (HA), and its metabolites in rat cerebrospinal fluid (CSF).

    PubMed

    Zhang, Yanhua; Tingley, F David; Tseng, Elaine; Tella, Max; Yang, Xin; Groeber, Elizabeth; Liu, Jianhua; Li, Wenlin; Schmidt, Christopher J; Steenwyk, Rick

    2011-07-15

    A UPLC-MS/MS assay was developed and validated for simultaneous quantification of acetylcholine (ACh), histamine (HA), tele-methylhistamine (t-mHA), and tele-methylimidazolacetic acid (t-MIAA) in rat cerebrospinal fluid (CSF). The biological stability of ACh in rat CSF was investigated. Following fit-for-purpose validation, the method was applied to monitor the drug-induced changes in ACh, HA, t-mHA, and t-MIAA in rat CSF following administration of donepezil or prucalopride. The quantitative method utilizes hydrophilic interaction chromatography (HILIC) Core-Shell HPLC column technology and a UPLC system to achieve separation with detection by positive ESI LC-MS/MS. This UPLC-MS/MS method does not require extraction or derivatization, utilizes a stable isotopically labeled internal standard (IS) for each analyte, and allows for rapid throughput with a 4 min run time. Without an acetylcholinesterase (AChE) inhibitor present, ACh was found to have 1.9±0.4 min in vitro half life in rat CSF. Stability studies and processing modification, including the use of AChE inhibitor eserine, extended this half life to more than 60 min. The UPLC-MS/MS method, including stabilization procedure, was validated over a linear concentration range of 0.025-5 ng/mL for ACh and 0.05-10 ng/mL for HA, t-mHA, and t-MIAA. The intra-run precision and accuracy for all analytes were 1.9-12.3% CV and -10.2 to 9.4% RE, respectively, while inter-run precision and accuracy were 4.0-16.0% CV and -5.3 to 13.4% RE, respectively. By using this developed and validated method, donepezil caused increases in ACh levels at 0.5, 1, 2, and 4h post dose as compared to the corresponding vehicle group, while prucalopride produced approximately 1.6- and 3.1-fold increases in the concentrations of ACh and t-mHA at 1h post dose, respectively, compared to the vehicle control. Overall, this methodology enables investigations into the use of CSF ACh and HA as biomarkers in the study of these neurotransmitter systems

  19. 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.

  20. 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.

  1. Cerebrospinal fluid culture

    MedlinePlus

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

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

    PubMed

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

    1995-01-01

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

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

    PubMed

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

    1998-03-01

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

  4. 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

  5. Imhotep and the discovery of cerebrospinal fluid.

    PubMed

    Blomstedt, Patric

    2014-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    1992-01-01

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

  8. Cerebrospinal fluid otorhinorrhea due to cochlear dysplasias.

    PubMed

    Syal, Rajan; Tyagi, Isha; Goyal, Amit

    2005-07-01

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

  9. Endoscopic management of cerebrospinal fluid rhinorrhea.

    PubMed

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

    2016-01-01

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

  10. 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

  11. Tegmental defects and cerebrospinal fluid otorrhea.

    PubMed

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

    2001-01-01

    Congenital tegmental defects that present as unsuspected cerebrospinal fluid (CSF) otorrhea are diagnostic and therapeutic challenges. We reviewed 5 such patients to determine an optimal strategy for evaluation. Five patients presented with watery otorrhea, 4 of them after ventilation tube placement, and only 1 with rhinorrhea. The preoperative analysis of middle ear effusion for beta(2)-transferrin was positive in 2/4, equivocal in 1/4 and false negative in 1/4. Computerized tomography (CT) revealed nonspecific tegmental defects in all 5 patients. Magnetic resonance imaging (MRI) demonstrated meningoencephalocele in 3/5 and dural irregularity in 1/5. Tegmental defects were confirmed at surgery in all cases, demonstrating meningocele or arachnoid granulations in 2/5 and encephalocele in 2/5 patients. We recommend a combination of beta(2)-transferrin analysis to verify CSF, high resolution CT (axial and coronal planes) to diagnose tegmental defects, and MRI (multiplanar) to evaluate the type of herniation. A combination mastoid and middle fossa approach for definitive repair is suggested. PMID:11174062

  12. 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

  13. Massive Cerebrospinal Fluid Leak of the Temporal Bone.

    PubMed

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

    2016-01-01

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

  14. 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

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

    PubMed

    Illing, Elisa A; Woodworth, Bradford A

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-08-28

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

  18. 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

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

    PubMed Central

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

    2015-01-01

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

  20. 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...

  1. A new look at cerebrospinal fluid movement

    PubMed Central

    2014-01-01

    Brinker et al. extensively reviewed recent findings about CSF circulation in a recent article: “A new look at cerebrospinal circulation”, but did not analyze some important available data in sufficient detail. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. These are based on: a) physiological oscillations of arterial and venous blood during cranio-spinal blood circulation; b) respiratory activity, and c) body activity and posture. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. It seems that efflux transport systems at capillary endothelium may be more important for brain homeostasis than the removal of metabolites by CSF flow. Thus, when discussing the CSF dynamics we suggest that a more appropriate term would be CSF movement rather than CSF circulation. PMID:25089184

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

    PubMed Central

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

    1984-01-01

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

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

    PubMed

    Hoppe, F; Hagen, R; Hofmann, E

    1997-01-01

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

  4. 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

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

    PubMed

    Mamoojee, Yaasir; Chadwick, David

    2011-12-01

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

  6. Cerebral spinal fluid (CSF) collection

    MedlinePlus

    ... tumor, abscess , stroke , or demyelinating disease (such as multiple sclerosis). Red blood cells in the CSF sample may ... levels may be due to diseases such as multiple sclerosis , neurosyphilis , or Guillain-Barré syndrome . Additional conditions under ...

  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. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

    PubMed Central

    2009-01-01

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

  9. 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.

  10. 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

  11. CSF oligoclonal banding - slideshow

    MedlinePlus

    ... presentations/100145.htm CSF oligoclonal banding - series—Normal anatomy ... Overview The cerebrospinal fluid (CSF) serves to supply nutrients to the central nervous system (CNS) and collect waste products, as well as ...

  12. Vitamin B6 in Plasma and Cerebrospinal Fluid of Children

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Wiltfang, Jens

    2015-04-01

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

  14. 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

  15. 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

  16. Amino acid composition of cerebrospinal fluid in actue neuroinfections in children.

    PubMed

    Buryakova, A V; Sytinsky, I A

    1975-01-01

    A survey of the cerebrospinal fluid (CSF) amino acids, glutamine, and glutamic and gamma-aminobutyric (GABA) acids was made in 168 children, aged 1 to 14 years, with various neurological infections. The glutamic acid and glutamine concentrations in the CSF of children with severe forms of acute serous and bacterial meningitis were about three to four times as great as in controls. The indices returned almost to normal during recovery. GABA is absent in normal CSF, but appeared in the CSF of patients with bacterial meningitis. Its determination may be used as an additional test to differentiate between serous and bacterial meningitis. PMID:234733

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    1983-09-01

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

  19. CSF myelin basic protein

    MedlinePlus

    CSF myelin basic protein is a test to measure the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF). The CSF ... less than 4 ng/mL of myelin basic protein in the CSF. Normal value ranges may vary ...

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. Surgical challenge: endoscopic repair of cerebrospinal fluid leak

    PubMed Central

    2012-01-01

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

  3. CSF analysis

    MedlinePlus

    Cerebrospinal fluid analysis ... Analysis of CSF can help detect certain conditions and diseases. All of the following can be, but ... An abnormal CSF analysis result may be due to many different causes, ... Encephalitis (such as West Nile and Eastern Equine) Hepatic ...

  4. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2015-10-01

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

  6. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

    Objective To describe our experience of cerebrospinal fluid (CSF) rhinorrhea management. Design Retrospective. Setting Charing Cross Hospital, London, a tertiary referral center. Participants Fifty-four patients with CSF rhinorrhea managed from 2003 to 2011. Main outcome measures Surgical technique; Recurrence. Results Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with spontaneous and two with traumatic leaks had previous failed repairs in other units. Success rates after first and second surgery were 93% and 100%, respectively. Mean follow-up was 21 months. Four patients, all of spontaneous etiology, had recurrences; three of these underwent successful second repair with three layered technique, and the fourth had complete cessation of the leak after gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic three-layered repair since then averted any further failure in the following 7 years. Mean body mass index was 34.0 kg/m2 in spontaneous and 27.8 kg/m2 in traumatic cases (p < 0.05). Fifty percent of spontaneous leaks were from the cribriform plate, 22% sphenoid, 14% ethmoid, and 14% frontal sinus. In the traumatic CSF leak group: 33.3% were from the cribriform plate, 33.3% sphenoid, 22.2% ethmoid, and 11.1% frontal. Conclusion Endoscopic CSF fistula closure is a safe and effective operation. All sites of leak can be accessed endoscopically. We recommend the use of an anatomic three-layered closure in difficult cases. PMID:24436890

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

    NASA Astrophysics Data System (ADS)

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

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

  10. Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-01-01

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

  12. A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

    PubMed

    Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

    2015-11-01

    In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. PMID:26247808

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1990-01-01

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

  15. Spontaneous sphenoid sinus cerebrospinal fluid leak and meningoencephalocele - are they due to patent Sternberg's canal?

    PubMed

    Tomaszewska, Magdalena; Brożek-Mądry, Eliza; Krzeski, Antoni

    2015-07-01

    Sternberg's canal is a congenital bony defect in the lateral wall of the sphenoid sinus. If it persists to adulthood, it may become a source of spontaneous cerebrospinal fluid leak (CSF) and meningoencephalocele. The aim of the study was to describe the authors' experience and review articles related to spontaneous sphenoid sinus CSF leaks and Sternberg's canal. We analysed patients managed surgicallly due to sphenoid sinus CSF leak and performed a PubMed database search. Two female patients with spontaneous CSF leak of sphenoid origin were found. Both patients underwent surgery with the endoscopic endonasal approach, and the defect was closed using the multi-layer technique. Twelve articles related to CSF leaks of sphenoid origin (due to Sternberg's canal) were found in the PubMed database. Lines of lesser resistance within sphenoid bone may underlie CSF leak pathology together with intracranial hypertension. The endoscopic transnasal approach to the sphenoid sinus is an excellent alternative to standard transcranial procedures. PMID:26240642

  16. 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.

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

    PubMed

    Reiber, Hansotto

    2016-06-01

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

  18. Spontaneous sphenoid sinus cerebrospinal fluid leak and meningoencephalocele – are they due to patent Sternberg's canal?

    PubMed Central

    Tomaszewska, Magdalena; Krzeski, Antoni

    2014-01-01

    Sternberg's canal is a congenital bony defect in the lateral wall of the sphenoid sinus. If it persists to adulthood, it may become a source of spontaneous cerebrospinal fluid leak (CSF) and meningoencephalocele. The aim of the study was to describe the authors’ experience and review articles related to spontaneous sphenoid sinus CSF leaks and Sternberg's canal. We analysed patients managed surgicallly due to sphenoid sinus CSF leak and performed a PubMed database search. Two female patients with spontaneous CSF leak of sphenoid origin were found. Both patients underwent surgery with the endoscopic endonasal approach, and the defect was closed using the multi-layer technique. Twelve articles related to CSF leaks of sphenoid origin (due to Sternberg's canal) were found in the PubMed database. Lines of lesser resistance within sphenoid bone may underlie CSF leak pathology together with intracranial hypertension. The endoscopic transnasal approach to the sphenoid sinus is an excellent alternative to standard transcranial procedures. PMID:26240642

  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. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

    PubMed Central

    Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

    2008-01-01

    This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory

  1. Testing for Herpes Simplex Virus in Low-Volume Cerebrospinal Fluid Samples: Comparison of Three Protocols To Optimize Detection

    PubMed Central

    Espy, Mark J.; Irish, Cole L.

    2015-01-01

    Detection of herpes simplex virus 1 and 2 (HSV-1 and HSV-2) in cerebrospinal fluid (CSF) is a medical emergency and requires rapid, sensitive testing. However, the volume of CSF received for microbiological studies may be limited, especially from young children. In this study, we compared three testing protocols to our routine real-time PCR method to determine the most sensitive approach for detecting HSV-1 and HSV-2 in low-volume (≤100 μl) CSF. PMID:26400783

  2. CSF oligoclonal banding

    MedlinePlus

    ... the cerebrospinal fluid (CSF). CFS is the clear fluid that flows in the space around the spinal cord and brain. Oligoclonal bands are proteins called immunoglobulins. The ... system. Oligoclonal bands may be a sign of multiple sclerosis.

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

    PubMed

    Oreshnikov, E V; Oreshnikov, S F

    2015-01-01

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

  4. 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.

  5. Endoscopic Endonasal Repair of Spontaneous and Traumatic Cerebrospinal Fluid Rhinorrhea: A Review and Local Experience.

    PubMed

    Gonen, Lior; Monteiro, Eric; Klironomos, George; Alghonaim, Yazeed; Vescan, Allan; Zadeh, Gelareh; Gentili, Fred

    2015-07-01

    This article presents an overview of endoscopic endonasal repair of cerebrospinal fluid (CSF) rhinorrhea. In recent years, endoscopic repair has become the standard of care for managing this condition, because it gradually replaces the traditional open transcranial approach. Discussion includes the etiologic classification of CSF rhinorrhea, management paradigm for each category, diagnosis algorithm, comprehensive description of the surgical technique, and an updated review of the literature regarding the safety and efficacy of this procedure. In addition, the authors present their experience, including 2 surgical videos demonstrating endoscopic repair of CSF rhinorrhea in 2 distinct clinical scenarios. PMID:26141354

  6. The effect of chronic osmotic disturbance on the concentrations of cations in cerebrospinal fluid.

    PubMed

    Bradbury, M W; Kleeman, C R

    1969-09-01

    1. Adult cats were rendered hypo- and hypernatraemic by peritoneal dialysis. These states were maintained for periods of 2-5 days.2. The concentrations in cerebrospinal fluid (c.s.f.) of the cations, potassium, calcium and magnesium all decreased in the hyponatraemic animals and increased in the hypernatraemic animals. These shifts in c.s.f. cation concentrations did not relate to plasma changes in the same cations, which were often in the opposite direction.3. The relations of the cation concentrations to c.s.f. sodium were not linear and, in the cases of calcium and magnesium, the relevant cation concentration related better to the square rather than the first power of the c.s.f. sodium concentration.4. Brain water changed much less in the hypo- and hypernatraemic animals than might be anticipated from the shifts in blood osmolarity, plasma sodium concentration and muscle water.5. Isotonicity of the fluids in brain with blood plasma and c.s.f. appeared to be largely maintained by loss or gain of sodium and chloride ions by this tissue.6. The c.s.f. results may be partly due to a constant influx of the cation in question being diluted with more formed c.s.f. in hyponatraemia and less c.s.f. in hypernatraemia, but the deviations from linearity in the plots of c.s.f. cation against c.s.f. sodium suggest the influence of other factors. PMID:5352043

  7. Pulsatile cerebrospinal fluid dynamics in the human brain.

    PubMed

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

    2005-04-01

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

  8. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. 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

  15. 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

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

    PubMed

    Bottan, Simone; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2012-06-01

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

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

    PubMed

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

    2016-01-01

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

  18. 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.

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

    PubMed

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

    2016-01-01

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

  20. Refractory Thoracolumbar Cerebrospinal Fluid Leak after Multiple Spinal Ependymoma Resections Treated with External Ventricular Drainage.

    PubMed

    Galgano, Michael A; Hazama, Ali; Deshaies, Eric M

    2016-02-01

    Study Design Case report. Objective Temporary external ventricular drainage for refractory thoracolumbar cerebrospinal fluid (CSF) leak is not reported in the literature. We describe a recent case that utilized this technique. Methods Retrospective review of the patient's case notes was performed and the literature on this subject reviewed. Results The patient underwent multiple complex spinal surgeries for resection of innumerable metastatic ependymoma lesions. A case of significant refractory CSF leak developed and as a last resort a right frontal external ventricular drain was placed. The CSF leak ceased, and the patient was eventually discharged home without further complication. Conclusion External ventricular drainage can be a viable option for temporary proximal CSF diversion to treat refractory thoracolumbar CSF leaks. PMID:26835210

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

    PubMed

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

    1990-11-01

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

  2. Efavirenz pharmacokinetics in cerebrospinal fluid and plasma over a 24-hour dosing interval.

    PubMed

    Yilmaz, Aylin; Watson, Victoria; Dickinson, Laura; Back, David

    2012-09-01

    We determined the pharmacokinetics of efavirenz in plasma and cerebrospinal fluid (CSF) over a 24-h dosing interval in a patient who had undergone a lumbar drain because of cryptococcal meningitis. Drug concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry in paired CSF (n = 24) and plasma (n = 25) samples. The median plasma efavirenz concentration was 3,718 ng/ml (range, 2,439 to 4,952), and the median CSF concentration was 16.3 ng/ml (range, 7.3 to 22.3). The CSF/plasma area-under-the-curve ratio was 0.0044 corresponding to a CSF penetration of 0.44% of plasma. PMID:22687515

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2016-03-01

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

  5. 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

  6. 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

  7. Development and functions of the choroid plexus–cerebrospinal fluid system

    PubMed Central

    Lun, Melody P.; Monuki, Edwin S.; Lehtinen, Maria K.

    2015-01-01

    The choroid plexus (ChP) is the principal source of cerebrospinal fluid (CSF), which has accepted roles as a fluid cushion and a sink for nervous system waste in vertebrates. Various animal models have provided insight into how the ChP–CSF system develops and matures. In addition, recent studies have uncovered new, active roles for this dynamic system in the regulation of neural stem cells, critical periods and the overall health of the nervous system. Together, these findings have brought about a paradigm shift in our understanding of brain development and health, and have stimulated new initiatives for the treatment of neurological disease. PMID:26174708

  8. Three-dimensional cerebrospinal fluid flow within the human ventricular system.

    PubMed

    Howden, L; Giddings, D; Power, H; Aroussi, A; Vloeberghs, M; Garnett, M; Walker, D

    2008-04-01

    Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a "nesting" approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant. PMID:18297492

  9. Meningeal haemorrhage secondary to cerebrospinal fluid drainage during thoracic endovascular aortic repair

    PubMed Central

    Mancio, Jennifer; Pires-Morais, Gustavo; Bettencourt, Nuno; Oliveira, Marco; Santos, Lino; Melica, Bruno; Rodrigues, Alberto; Braga, José Pedro; Ribeiro, Vasco Gama

    2014-01-01

    Thoracic endovascular aortic repair (TEVAR) has shown lower mortality compared with open surgical repair (OSR). However, the risk of spinal cord ischaemia (SCI) remains similar than OSR. As a prophylactic measure to reduce the risk of SCI, cerebrospinal fluid (CSF) drainage has been widely used in OSR. In TEVAR, the utility of this adjunct is still controversial. We report a case of a 56-year-old man referred for TEVAR for a descending thoracic aneurysm that previously underwent an abdominal aneurysmectomy with aortobifemoral bypass graft. On the day before, a lumbar cerebrospinal drain was placed prophylactically. Forty-eight hours after the procedure, meningeal symptoms without neurological deficits developed. Clinical investigation revealed meningeal haemorrhage. Therapy with nimodipine was initiated with symptomatic relief. Evidence from randomized controlled trials supporting the role of CSF drainage in TEVAR is still lacking. We discuss the current recommendations, potential benefits and risks and cautions associated with CSF drainage in TEVAR. PMID:25988028

  10. 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

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed

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

    2005-05-01

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

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

    PubMed

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

    1994-07-01

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

  14. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines

    PubMed Central

    Warrington, Junie P

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Warrington, Junie P

    2015-11-01

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

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

    PubMed

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

    2016-07-15

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

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

    PubMed 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

  19. Studies on homocarnosine in cerebrospinal fluid in infancy and childhood. Part II. Homocarnosine levels in cerebrospinal fluid from children with epilepsy, febrile convulsion or meningitis.

    PubMed

    Takahashi, H

    1981-01-01

    To clarify the pathophysiological role of homocarnosine in the cerebrospinal fluid (CSF) in children, homocarnosine levels in CSF were determined in patients with epilepsy (32 cases), febrile convulsion (5 cases) and meningitis (42 cases) with a high speed amino acid autoanalyzer (Hitachi Co.). Mean homocarnosine levels in CSF of controlled epileptic children, uncontrolled epileptic children and febrile convulsion cases were 0.61 +/- 0.25 mumol/dl, 1.03 +/- 0.37 mumol/dl and 1.09 +/- 0.04 mumol/dl, respectively. High homocarnosine levels in CSF of children with uncontrolled epilepsy or febrile convulsion may indicate the reduced turnover rate from homocarnosine to GABA. In patients with meningitis, the unconscious states were accompanied by significantly lower homocarnosine levels in CSF (0.39 +/- 0.20 mumol/dl) than those in the patients with clear conscious states (0.9 +/- 0.31 mumol/dl, however, in patients with clear conscious states homocarnosine in CSF were almost the same as those of normal children (0.89 +/- 0.23 mumol/dl). These data suggest that homocarnosine in CSF might be related to the convulsive tendency and consciousness. PMID:7283086

  20. Cerebrospinal fluid pressure and the eye.

    PubMed

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

    2016-01-01

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

  1. Extracranial repair of cerebrospinal fluid otorhinorrhea

    SciTech Connect

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

    1991-02-01

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

  2. Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics

    SciTech Connect

    Miller, K.T.; Wilkinson, D.S.

    1989-01-01

    Pharmacokinetic parameters of the distribution and elimination of intracerebroventricularly administered methotrexate (MTX) were evaluated in three patients with meningeal carcinomatosis. Abnormal cerebrospinal fluid (CSF) flow dynamics, which were not otherwise clinically evident, were diagnosed by 111In-diethylenetriaminepentaacetate radionuclide imaging. Alterations in CSF flow resulted in large changes in MTX distribution. Reduced cortical convexity (type III), spinal subarachnoid (type II), or ventricular (type I) CSF flow resulted in a prolongation of the single-pass mean residence time of MTX in the peripheral compartment by as much as eightfold and a reduction in intercompartmental clearance by 94-99%. Leptomeningeal carcinomatosis can affect both CSF MTX distribution and elimination, each to a different extent, within the same patient. Total MTX clearance from the CSF was reduced by 79-93% in the patients studied. A two-compartment pharmacokinetic model, with elimination occurring from the peripheral compartment, gave values for the distribution rate constant from the central to the peripheral compartment (k12), which decreased with the extent of CSF flow abnormality. However, the elimination rate constant from the peripheral compartment (k20) was reduced to an extent apparently independent of CSF flow abnormality (percentage reduction in k12 and k20, respectively: type III, 18 and 66; type II, 67 and 86; type I, 78 and 48). Inadequate distribution and locally high concentrations of MTX within the CSF may contribute to therapeutic failure and neurotoxicity. Monitoring of MTX levels in the CSF may be deceiving when samples are drawn from the site of injection, since the distribution kinetics are altered by abnormal CSF flow dynamics.

  3. Molecular Detection of Leptospira in Two Returned Travelers: Higher Bacterial Load in Cerebrospinal Fluid versus Serum or Plasma

    PubMed Central

    Waggoner, Jesse J.; Soda, Elizabeth A.; Seibert, Ryan; Grant, Philip; Pinsky, Benjamin A.

    2015-01-01

    Leptospirosis is a potentially severe illness in returned travelers. Patients often present with fever, headache, and neck pain, which may lead to a workup for meningitis including the acquisition of cerebrospinal fluid (CSF). Although Leptospira DNA has been detected in CSF by polymerase chain reaction (PCR), little data exist regarding the utility of testing CSF in addition to serum or plasma obtained on presentation. In this report, we present two cases of leptospirosis in returned travelers presenting with fever and headache. Our first patient had neutrophilic meningitis, and Leptospira was detectable only in CSF obtained on admission. The second patient had a normal CSF profile, but Leptospira was detected in CSF at a bacterial load 5- to 10-fold higher than that in plasma. CSF is an important specimen for the diagnosis of Leptospira by molecular methods and may yield an actionable diagnosis in the absence of leptospiremia. PMID:26033024

  4. Molecular Detection of Leptospira in Two Returned Travelers: Higher Bacterial Load in Cerebrospinal Fluid Versus Serum or Plasma.

    PubMed

    Waggoner, Jesse J; Soda, Elizabeth A; Seibert, Ryan; Grant, Philip; Pinsky, Benjamin A

    2015-08-01

    Leptospirosis is a potentially severe illness in returned travelers. Patients often present with fever, headache, and neck pain, which may lead to a workup for meningitis including the acquisition of cerebrospinal fluid (CSF). Although Leptospira DNA has been detected in CSF by polymerase chain reaction (PCR), little data exist regarding the utility of testing CSF in addition to serum or plasma obtained on presentation. In this report, we present two cases of leptospirosis in returned travelers presenting with fever and headache. Our first patient had neutrophilic meningitis, and Leptospira was detectable only in CSF obtained on admission. The second patient had a normal CSF profile, but Leptospira was detected in CSF at a bacterial load 5- to 10-fold higher than that in plasma. CSF is an important specimen for the diagnosis of Leptospira by molecular methods and may yield an actionable diagnosis in the absence of leptospiremia. PMID:26033024

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

    PubMed

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

    1985-05-01

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

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

    PubMed

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

    1985-04-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. CSF total protein

    MedlinePlus

    CSF total protein is a test to determine the amount of protein in your spinal fluid, also called cerebrospinal fluid (CSF). ... The normal protein range varies from lab to lab, but is typically about 15 to 60 mg/dL. Note: mg/dL = ...

  10. Primary Spontaneous Cerebrospinal Fluid Leaks and Idiopathic Intracranial Hypertension

    PubMed Central

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

    2014-01-01

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

  11. Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment.

    PubMed

    Sharma, R P; Faull, K; Javaid, J I; Davis, J M

    1995-05-01

    Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA. PMID:7639084

  12. 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

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

    PubMed Central

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

    2013-01-01

    Postoperative cerebrospinal fluid (CSF) rhinorrhea after septoplasty is a known entity resulting from errors in surgical technique and improper handling of the perpendicular plate of the ethmoid bone. When these occur, urgent management is necessary to prevent deleterious sequelae such as meningitis, intracranial abscess, and pneumocephalus. Encephaloceles are rare occurrences characterized by herniation of intracranial contents through a skull base defect that can predispose patients to CSF rhinorrhea. In this report, we present a case of CSF rhinorrhea occurring 2 weeks after septoplasty likely from manipulation of an occult anterior skull base encephalocele. To our knowledge, no previous similar case has been reported in the literature. Otolaryngologists should be aware of the possibility of occult encephaloceles while performing septoplasties because minimal manipulation of these entities may potentially result in postoperative CSF leakage. PMID:23772326

  14. [Revival of old diagnostic markers in the cerebrospinal fluid for the detection of infectious meningitis].

    PubMed

    Sakushima, Ken; Yabe, Ichiro; Sasaki, Hidenao

    2012-01-01

    Bacterial meningitis and tubercular meningitis are still neurological emergencies characterized by severe mortality and morbidity. Recent studies of meta-analysis have shown the usefulness of cerebrospinal fluid (CSF) lactate and CSF adenosine deaminase (ADA) as markers for the detection of bacterial meningitis and tubercular meningitis, respectively. CSF lactate has a high sensitivity and specificity for the diagnosis of bacterial meningitis, but the sensitivity can be reduced by antibiotic pretreatment. CSF-ADA has a moderate sensitivity but a high specificity and is reliable for the diagnosis of tubercular meningitis. These old diagnostic markers can be evaluated in resource-poor settings including small general hospitals and non-specialized hospitals for infectious diseases, and they can contribute to the quick and accurate diagnosis of infectious meningitis. PMID:22260972

  15. Dimethylarginine levels in cerebrospinal fluid of hyperacute ischemic stroke patients are associated with stroke severity.

    PubMed

    Brouns, Raf; Marescau, Bart; Possemiers, Ilse; Sheorajpanday, Rishi; De Deyn, Peter P

    2009-09-01

    We hypothesise that asymmetric and symmetric dimethylarginine (ADMA, SDMA) are released in cerebrospinal fluid (CSF) due to ischemia-induced proteolysis and that CSF dimethylarginines are related to stroke severity. ADMA and SDMA were measured in CSF of 88 patients with ischemic stroke or TIA within 24 h after stroke onset (mean 8.6 h) and in 24 controls. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission. Outcome was evaluated by institutionalization due to stroke and the modified Rankin scale. Dimethylarginine levels were higher in patients with stroke than in TIA patients, who had higher levels than controls and correlated with the NIHSS. Logistic regression analysis confirmed that dimethylarginines were independently associated with stroke severity. The SDMA/ADMA ratio did not differ significantly between controls and stroke patients. CSF dimethylarginine levels are increased in hyperacute ischemic stroke and are associated with stroke severity. PMID:19296217

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

    PubMed

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

    1979-03-01

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

  17. Chemical profiling of cerebrospinal fluid by multiple reaction monitoring mass spectrometry.

    PubMed

    Ferreira, Christina R; Yannell, Karen E; Mollenhauer, Brit; Espy, Ryan D; Cordeiro, Fernanda B; Ouyang, Z; Cooks, R G

    2016-09-21

    We report an accelerated biomarker discovery workflow and results of sample screening by mass spectrometry based on multiple reaction monitoring (MRM). This methodology shows promising initial results for the currently unsolved challenge of Parkinson's disease (PD) laboratory diagnosis by biomarker screening. Small molecules present in cerebrospinal fluid (CSF) at low parts per million levels are monitored using specific transitions connecting ion pairs. A set of such transitions constitutes a multidimensional chemical profile used to distinguish and characterize different CSF samples using multivariate statistical methods. PMID:27517482

  18. 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

  19. 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

  20. Immunohistochemical analysis of the cerebrospinal fluid for carcinomatous and lymphomatous leptomeningitis.

    PubMed Central

    Hovestadt, A.; Henzen-Logmans, S. C.; Vecht, C. J.

    1990-01-01

    To evaluate the sensitivity and specificity of immunohistochemical analysis in relation to the standard cytological examination of the cerebrospinal fluid (CSF) in patients with either a solid tumour or a haematological malignancy and possible leptomeningeal disease, 68 CSF-samples derived from 68 patients were examined. The sensitivity of immunohistochemical analysis was 0.54 and its specificity 0.98. Only one patient had a positive immunohistochemistry and a negative cytology. The gain of adding immunohistochemistry to cytology is nearly 8%. It is concluded that immunohistochemistry should not be used as a screening test for leptomeningeal disease in patients with cancer. PMID:2223585

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

    PubMed

    Baba, Murad; Tarar, Omer; Syed, Amer

    2016-01-01

    Introduction. Spontaneous nontraumatic pneumocephalus (PNC) and cerebrospinal fluid (CSF) leaks are both very uncommon conditions. We report a rare case of spontaneous pneumocephalus associated with CSF leak secondary to right sphenoid sinus bony defect without history of trauma. Case Description. 51-year-old Hispanic female with past medical history of hypertension and idiopathic intracranial hypertension (Pseudotumor Cerebri) presented to the emergency room complaining of headache and clear discharge from the right nostril. Physical examination was significant for right frontal sinus tenderness and clear discharge from right nostril. Computed Tomography (CT) scan of the brain showed moderate amount of extra-axial air within the right cerebral hemisphere indicative of pneumocephalus. CT scan of facial bones showed bony defect along the right sphenoid sinus with abnormal CSF collection. The patient was started on intravenous antibiotics for meningitis prophylaxis and subsequently underwent transsphenoidal repair of cerebrospinal fluid leak with abdominal fat graft. CSF rhinorrhea stopped completely after the surgery with near complete resolution of pneumocephalus before discharge. Conclusions. Early identification of pneumocephalus and surgical intervention can help decrease the morbidity and avoid possible complications. Idiopathic intracranial hypertension, although rare, can lead to CSF leak and pneumocepahlus. PMID:27217961

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

    PubMed Central

    Tarar, Omer; Syed, Amer

    2016-01-01

    Introduction. Spontaneous nontraumatic pneumocephalus (PNC) and cerebrospinal fluid (CSF) leaks are both very uncommon conditions. We report a rare case of spontaneous pneumocephalus associated with CSF leak secondary to right sphenoid sinus bony defect without history of trauma. Case Description. 51-year-old Hispanic female with past medical history of hypertension and idiopathic intracranial hypertension (Pseudotumor Cerebri) presented to the emergency room complaining of headache and clear discharge from the right nostril. Physical examination was significant for right frontal sinus tenderness and clear discharge from right nostril. Computed Tomography (CT) scan of the brain showed moderate amount of extra-axial air within the right cerebral hemisphere indicative of pneumocephalus. CT scan of facial bones showed bony defect along the right sphenoid sinus with abnormal CSF collection. The patient was started on intravenous antibiotics for meningitis prophylaxis and subsequently underwent transsphenoidal repair of cerebrospinal fluid leak with abdominal fat graft. CSF rhinorrhea stopped completely after the surgery with near complete resolution of pneumocephalus before discharge. Conclusions. Early identification of pneumocephalus and surgical intervention can help decrease the morbidity and avoid possible complications. Idiopathic intracranial hypertension, although rare, can lead to CSF leak and pneumocepahlus. PMID:27217961

  3. 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. PMID:26463525

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

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. Detection of free immunoglobulin light chains in cerebrospinal fluids of patients with central nervous system lymphomas.

    PubMed

    Schroers, Roland; Baraniskin, Alexander; Heute, Christoph; Kuhnhenn, Jan; Alekseyev, Andriy; Schmiegel, Wolff; Schlegel, Uwe; Pels, Hendrik-Johannes

    2010-09-01

    Diagnosis of central nervous system (CNS) lymphoma depends on histopathology of brain biopsies, because no reliable disease marker in the cerebrospinal fluid (CSF) has been identified yet. B-cell lymphomas such as CNS lymphomas are clonally restricted and express either kappa or lambda immunoglobulin light chains. The aim of this study was to find out a potential diagnostic value of free immunoglobulin light chains released into the CSF of CNS lymphoma patients. Kappa (kappa) and lambda (lambda) free immunoglobulin light chains (FLC) were measured in CSF and serum samples collected from 21 patients with primary and secondary CNS lymphomas and 14 control patients with different neurologic disorders. FLC concentrations and ratios were compared between patient groups and were further analyzed in correlation with clinical, cytopathological, and radiological findings. FLC concentrations for all patients were lower in CSF when compared to serum. In patients with CNS lymphoma, the FLC ratios in CSF were higher (range 392-0.3) compared to control patients (range 3.0-0.3). Irrespective of cytopathological proven lymphomatous meningitis, in 11/21 lymphoma CSF samples the FLC ratios were markedly above 3.0 indicating a clonally restricted B-cell population. Increased FLC ratios in CSF were found in those patients showing subependymal lymphoma contact as detected in magnetic resonance imaging. In summary, this is the first report demonstrating that a significant proportion of patients with CNS lymphomas display a markedly increased FLC ratio in the CSF. PMID:20528903

  8. 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

  9. 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. PMID:27142258

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

    PubMed Central

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

    2010-01-01

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

  11. Spontaneous cerebrospinal fluid leakage through fistulas at the clivus repaired with endoscopic endonasal approach

    PubMed Central

    Hayashi, Yasuhiko; Iwato, Masayuki; Kita, Daisuke; Fukui, Issei

    2015-01-01

    Background: Causes of cerebrospinal fluid (CSF) leakage are primarily traumatic or iatrogenic in origin. In contrast, spontaneous CSF leakage is somewhat rare, and detection of the fistula can be challenging. Meningitis associated with CSF leakage can be life threatening. It is therefore critical to surgically repair the fistula once the underlying cause has been accurately identified. Spontaneous CSF leakage located at the clivus is an extremely rare condition. Case Description: We present the case of a 38-year-old male with sudden-onset headache and subsequent disturbances of consciousness. The patient was diagnosed with severe meningitis caused by CSF leakage through fistulas at the clivus, which were clearly identified on dynamic imaging using high-resolution computed tomography (CT) with intrathecal injection of contrast medium. After the meningitis was resolved, successful endoscopic repair of the CSF fistula with autologous materials was performed. There has been no recurrence of meningitis for 5 years. Conclusion: Spontaneous CSF leakage at the clivus is an extremely rare condition. High-resolution CT cisternogram could accurately detect CSF leakage through the clivus. A transnasal endoscopic approach was a useful and reliable method of repairing the fistula at the clivus. PMID:26110086

  12. Effects of positive and negative human contacts and intranasal oxytocin on cerebrospinal fluid oxytocin.

    PubMed

    Rault, Jean-Loup

    2016-07-01

    Despite the popularity of oxytocin (OT) research for its role in social behavior, the relationship between the social environment and endogenous central OT remains poorly understood. This study investigated the effects of positive and negative human contacts and intranasal OT administration on OT concentration in the cerebrospinal fluid (CSF). The pig was used as a model, with repeated CSF sampling through a spinal catheter using a within-subject design. Positive human contact led to sustained CSF OT elevation in pigs over 120min which outlasted the 15min interaction. Furthermore, the frequency of positive interactions was correlated with CSF OT increase. This provides a neurophysiological basis to positive human-animal relationships, with OT preserving bonds within but also between species through interactions. Conversely, CSF OT concentration did not vary during or after negative contact with an unfamiliar person, supporting CSF OT as a biomarker of positive valence in the human-animal relationship context. Intranasal OT administration resulted in peak CSF OT within 10min, with approximately 0.001% of the administered dose reaching the CSF. The sensitivity of the oxytocinergic system to variations in the social environment is a worthy area of investigation for its scientific and clinical implications. In particular, positive interactions result in outlasting central OT release. PMID:27032064

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Proteomic Analysis of Cerebrospinal Fluid in Canine Cervical Spondylomyelopathy

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2012-01-01

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

  18. Bernoulli's Principle Applied to Brain Fluids: Intracranial Pressure Does Not Drive Cerebral Perfusion or CSF Flow.

    PubMed

    Schmidt, Eric; Ros, Maxime; Moyse, Emmanuel; Lorthois, Sylvie; Swider, Pascal

    2016-01-01

    In line with the first law of thermodynamics, Bernoulli's principle states that the total energy in a fluid is the same at all points. We applied Bernoulli's principle to understand the relationship between intracranial pressure (ICP) and intracranial fluids. We analyzed simple fluid physics along a tube to describe the interplay between pressure and velocity. Bernoulli's equation demonstrates that a fluid does not flow along a gradient of pressure or velocity; a fluid flows along a gradient of energy from a high-energy region to a low-energy region. A fluid can even flow against a pressure gradient or a velocity gradient. Pressure and velocity represent part of the total energy. Cerebral blood perfusion is not driven by pressure but by energy: the blood flows from high-energy to lower-energy regions. Hydrocephalus is related to increased cerebrospinal fluid (CSF) resistance (i.e., energy transfer) at various points. Identification of the energy transfer within the CSF circuit is important in understanding and treating CSF-related disorders. Bernoulli's principle is not an abstract concept far from clinical practice. We should be aware that pressure is easy to measure, but it does not induce resumption of fluid flow. Even at the bedside, energy is the key to understanding ICP and fluid dynamics. PMID:27165887

  19. Cerebrospinal fluid macrophage response to experimental cryptococcal meningitis: relationship between in vivo and in vitro measurements of cytotoxicity.

    PubMed Central

    Perfect, J R; Hobbs, M M; Granger, D L; Durack, D T

    1988-01-01

    The functional abilities of macrophages from cerebrospinal fluid (CSF) have so far been little studied. We examined the acquisition of activation characteristics by CSF macrophages during the course of experimental cryptococcal meningitis. CSF macrophages developed the ability for increased reactive oxidative intermediate (H2O2) production and tumor and fungal cytotoxicity. Despite having been activated, CSF macrophages could not inhibit the growth of Cryptococcus neoformans in vitro. Immunosuppression with cyclosporine, which eliminates the natural resistance of rabbits to cryptococcal meningitis, did not prevent or diminish H2O2 production by CSF macrophages but did reduce their tumoricidal activity. Activation of CSF macrophages appears to be an integral part of the central nervous system immune response to C. neoformans in this model, but alone is insufficient to eliminate C. neoformans from the central nervous system. PMID:3346075

  20. Intracranial pressure, its components and cerebrospinal fluid pressure-volume compensation.

    PubMed

    Kasprowicz, M; Lalou, D A; Czosnyka, M; Garnett, M; Czosnyka, Z

    2016-09-01

    Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant-rate infusion study. Due to the dynamic nature of ICP, a 'snapshot' manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure-volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction. PMID:26666840

  1. miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients

    PubMed Central

    Akers, Johnny C.; Ramakrishnan, Valya; Kim, Ryan; Phillips, Shirley; Kaimal, Vivek; Mao, Ying; Hua, Wei; Yang, Isaac; Fu, Chia-Chun; Nolan, John; Nakano, Ichiro; Yang, Yuanfan; Beaulieu, Martin; Carter, Bob S.; Chen, Clark C.

    2015-01-01

    Introduction Analysis of extracellular vesicles (EVs) derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of EVs in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in EVs derived from the serum and cerebrospinal fluid of glioblastoma patients. Methods EVs were isolated from glioblastoma cell lines as well as the plasma and CSF of glioblastoma patients. The microvesicle subpopulation was isolated by pelleting at 10,000×g for 30 min after cellular debris was cleared by a 2,000×g (20 min) spin. The exosome subpopulation was isolated by pelleting the microvesicle supernatant at 120,000×g (120 min). qRT-PCR was performed to examine the distribution of miR-21, miR-103, miR-24, and miR-125. Global miRNA profiling was performed in select glioblastoma CSF samples. Results In plasma and cell line derived EVs, the relative abundance of miRNAs in exosome and microvesicles were highly variable. In some specimens, the majority of the miRNA species were found in exosomes while in other, they were found in microvesicles. In contrast, CSF exosomes were enriched for miRNAs relative to CSF microvesicles. In CSF, there is an average of one molecule of miRNA per 150-25,000 EVs. Conclusion Most EVs derived from clinical biofluids are devoid of miRNA content. The relative distribution of miRNA species in plasma exosomes or microvesicles is unpredictable. In contrast, CSF exosomes are the major EV compartment that harbor miRNAs. PMID:25903655

  2. 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

  3. Cellular Immune Activation in Cerebrospinal Fluid From Ugandans With Cryptococcal Meningitis and Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Meya, David B.; Okurut, Samuel; Zziwa, Godfrey; Rolfes, Melissa A.; Kelsey, Melander; Cose, Steve; Joloba, Moses; Naluyima, Prossy; Palmer, Brent E.; Kambugu, Andrew; Mayanja-Kizza, Harriet; Bohjanen, Paul R.; Eller, Michael A.; Wahl, Sharon M.; Boulware, David R.; Manabe, Yuka C.; Janoff, Edward N.

    2015-01-01

    Background. Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood. Methods. We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10). Results. At diagnosis, highly activated CD8+ T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4+ T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood. Conclusions. After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4+ T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS. PMID:25492918

  4. MiRNA profiles in cerebrospinal fluid from patients with central hypersomnias.

    PubMed

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine; Modvig, Signe; Kornum, Birgitte Rahbek; Gammeltoft, Steen; Jennum, Poul J

    2014-12-15

    MicroRNAs (miRNAs) are involved in the pathogenesis of many human diseases, including some neurological disorders. Recently, we have reported dysregulated miRNAs in plasma from patients with central hypersomnias including type 1 and type 2 narcolepsy, and idiopathic hypersomnia. This study addressed whether miRNA levels are altered in the cerebrospinal fluid (CSF) of patients with central hypersomnias. We conducted high-throughput analyses of miRNAs in CSF from patients using quantitative real-time polymerase chain reaction panels. We identified 13, 9, and 11 miRNAs with a more than two-fold change in concentration in CSF from patients with type 1 and type 2 narcolepsy and idiopathic hypersomnia, respectively, compared with matched healthy controls. Most miRNAs differed in more than one of the sleep disorders. However, all miRNAs were detected at low levels in CSF and varied between individuals. None of them showed significant differences in concentrations between groups after correcting for multiple testing, and none could be validated in an independent cohort. Nevertheless, approximately 60% of the most abundant miRNAs in the profile reported here have previously been identified in the CSF of healthy individuals, showing consistency with previous miRNA profiles found in CSF. In conclusion, we were not able to demonstrate distinct levels or patterns of miRNAs in CSF from central hypersomnia patients. PMID:25451005

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

    PubMed

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

    1994-12-01

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

  6. Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations.

    PubMed

    Ponto, James A; Graham, Michael M

    2014-01-01

    OBJECTIVE To confirm the anticipated image quality and absence of adverse reactions in patients undergoing clinical practice cerebrospinal fluid (CSF) leak imaging procedures using technetium Tc-99m pyrophosphate (PYP). METHODS Following the recent discontinuation of preservative-free calcium trisodium diethylene triamine pentaacetic acid kits, PYP was selected as a suitable alternative for CSF leak imaging procedures. Procedures were established for its preparation and dispensing, paying special attention to safety considerations, and its use in clinical practice was implemented. Medical records, including images, were reviewed for the first 15 patients undergoing clinical practice CSF imaging procedures using Tc-99m PYP to confirm anticipated image quality and absence of adverse effects. RESULTS Review of CSF leak imaging procedures using Tc-99m PYP in 15 patients showed images to be of uniformly high quality. The vast majority of injected radiopharmaceutical remained in the CSF throughout the duration of the imaging procedure, allowing visualization of CSF leaks. Only a small amount of Tc-99m PYP diffused into the blood with resultant uptake on the skeleton and excretion into the urine, which did not interfere with image interpretation. No adverse reactions were noted in any of the patients. CONCLUSION With proper attention to safety considerations, Tc-99m PYP is a safe and effective alternative for performing CSF leak imaging procedures. PMID:24257695

  7. 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

  8. Anti-rabies virus IgM in serum and cerebrospinal fluid from rabid dogs.

    PubMed

    Tingpalapong, M; Hoke, C H; Ward, G S; Burke, D S; Elwell, M R; Lohytyothin, S; Saisombat, S

    1986-12-01

    An anti-rabies IgM antibody capture radio immunoassay was used to test serum and cerebrospinal fluid from 37 dogs held in quarantine for suspicion of rabies. Rabies was confirmed in dogs that died by mouse inoculation and subsequent examination of mouse brains by fluorescent antibody technique to detect rabies antigen. The mean counts per minute (CPM) of iodinated anti-rabies gamma globulin coupled IgM rabies antibody in CSF and serum from rabid dogs were significantly higher than in CSF and serum from non-rabid dogs. Mean CPM from rabid dogs was greater in CSF than in sera, in contrast with non-rabid dogs, from which mean cpm was higher in sera than CSF, suggesting that antibody may have been synthesized in the CSF. To evaluate this test further, a dog was infected by rabies virus, and serial serum and CSF specimens were collected until the time of death. IgM anti-rabies antibody developed in the CSF and serum 29 days following infection, and rose just before the dog died of rabies on day 34. The rabies MAC RIA is potentially useful as a diagnostic method in quarantined dogs with rabies-like illness. Perhaps more importantly, it may be applied to better understand the immunopathogenicity of rabies. PMID:3576284

  9. Cerebrospinal Fluid Leakage after Thoracic Decompression

    PubMed Central

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

    2016-01-01

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

  10. The choroid plexus-cerebrospinal fluid interface in Alzheimer's disease: more than just a barrier

    PubMed Central

    Balusu, Sriram; Brkic, Marjana; Libert, Claude; Vandenbroucke, Roosmarijn E.

    2016-01-01

    The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial (CPE) cells surrounding fenestrated capillaries. These CPE cells not only form an anatomical barrier, called the blood-cerebrospinal fluid barrier (BCSFB), but also present an active interface between blood and cerebrospinal fluid (CSF). CPE cells perform indispensable functions for the development, maintenance and functioning of the brain. Indeed, the primary role of the choroid plexus in the brain is to maintain homeostasis by secreting CSF which contains different molecules, such as nutrients, neurotrophins, and growth factors, as well as by clearing toxic and undesirable molecules from CSF. The choroid plexus also acts as a selective entry gate for leukocytes into the brain. Recent findings have revealed distinct changes in CPE cells that are associated with aging and Alzheimer's disease. In this review, we review some recent findings that highlight the importance of the CPE-CSF system in Alzheimer's disease and we summarize the recent advances in the regeneration of brain tissue through use of CPE cells as a new therapeutic strategy. PMID:27212900

  11. 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

  12. 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. PMID:16180222

  13. Adrenocorticotropic hormone in serial cerebrospinal fluid in man - Subject to acute regulation by the hypothalamic-pituitary-adrenocortical system?

    PubMed

    Kellner, Michael; Wortmann, Viola; Salzwedel, Cornelie; Kober, Daniel; Petzoldt, Martin; Urbanowicz, Tatiana; Pulic, Mersija; Boelmans, Kai; Yassouridis, Alexander; Wiedemann, Klaus

    2016-05-30

    Acute regulation of adrenocorticotropic hormone (ACTH) in cerebrospinal fluid (CSF) by the hypothalamic-pituitary-adrenocortical system has not been investigated in man. In a pilot study in healthy male volunteers we measured ACTH every twenty minutes in serial CSF for three hours after an intravenous placebo, hydrocortisone (100mg) or insulin (2mg/kg) injection. No acute inhibitory or stimulatory effects of these interventions were discovered. Our results corroborate previous findings in rhesus monkeys. The regulation of CSF ACTH and its potential relevance for behavioral alterations in health and disease (e.g. major depression or anorexia nervosa) in humans need further study. PMID:27031591

  14. T cell acute lymphoblastic leukaemia presenting with sudden onset right oculomotor nerve palsy with normal neuroradiography and cerebrospinal fluid studies

    PubMed Central

    Bhatt, Vijaya Raj; Naqi, Muniba; Bartaula, Rajiv; Murukutla, Srujitha; Misra, Sulagna; Popalzai, Muhammad; Paramanathan, Kavitha; Dai, Qun

    2012-01-01

    Leptomeningeal disease presenting with neurological dysfunction is not uncommon in leukaemia. However, it is often accompanied by abnormalities in cerebrospinal fluid (CSF) studies and/or neuroradiography. Here, the authors describe a case of a young patient presenting with sudden onset right oculomotor nerve palsy with normal neuroradiography and CSF studies, who was subsequently diagnosed to have T cell acute lymphoblastic leukaemia (T-ALL). This case highlights that neurological manifestations can be the initial presenting feature of T-ALL and can occur suddenly despite normal neuroradiography and initial CSF studies. PMID:22605802

  15. Herpes Zoster Meningitis Presenting With a Cerebrospinal Fluid Leukemoid Reaction in an Adolescent With preB-ALL in Remission.

    PubMed

    Adachi, Kristina; Song, Sophie X; Kao, Roy L; Van Dyne, Elizabeth; Kempert, Pamela; Deville, Jaime G

    2016-08-01

    A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia. PMID:27322719

  16. EBNA1 antigen-specific CD8+ T cells in cerebrospinal fluid of patients with multiple sclerosis.

    PubMed

    Erdur, Hebun; Scholz, Veronika; Streitz, Mathias; Hammer, Markus; Meisel, Christian; Schönemann, Constanze; Wandinger, Klaus-Peter; Rosche, Berit

    2016-05-15

    Epidemiological data suggests that Epstein-Barr virus may be involved in the pathogenesis of Multiple Sclerosis (MS). We aimed to determine the frequency of CD8+ T cells specific for one EBNA1-derived epitope (HPVGEADYFEY) in cerebrospinal fluid (CSF) and blood of patients with MS and other inflammatory neurological diseases (OIND). The frequency of specific CD8+ T cells was assessed by HLA-class-I-binding pentamers restricted to HLA-B35. The frequency of HPVGEADYFEY-specific CD8+ T cells did neither differ significantly in blood nor CSF in MS compared to OIND, but was consistently higher in CSF compared to blood regardless of diagnosis. PMID:27138093

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

    PubMed Central

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

    2013-01-01

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

  18. Exercise-induced changes of cerebrospinal fluid vascular endothelial growth factor in adult chronic hydrocephalus patients.

    PubMed

    Yang, Jun; Shanahan, Kaitlyn J; Shriver, Leah P; Luciano, Mark G

    2016-02-01

    Vascular endothelial growth factor (VEGF) is a growth factor demonstrated to be a key factor in cerebral angiogenesis and neurogenesis. It has been considered a critical component in hippocampus neurogenesis and memory formation and has been observed to increase in the rat hippocampus after exercise. We previously found increased VEGF levels in experimental chronic hydrocephalus in several brain areas and cerebrospinal fluid (CSF), suggesting a role in the adaption to chronic hypoxia. Here we investigate the ability of moderate exercise to increase CSF-VEGF levels in adult chronic hydrocephalus patients. Lumbar CSF samples were collected from 17 normal pressure hydrocephalus patients. During CSF collection, 11 patients (exercise group) underwent a standard in-room occupational therapy session; six patients (no-exercise group) did not undergo a physical therapy session. CSF-VEGF levels were evaluated for increase related to exercise and the clinical response to CSF drainage. CSF-VEGF levels in the exercise group demonstrated significant increases 1-3 hours post-exercise compared with the levels 1-2 hours pre-exercise (p=0.04), and also showed significantly higher levels than the no-exercise groups (p=0.03). The post-exercise CSF-VEGF level in the group that did not clinically improve was significantly higher than both their own pre-exercise level (p=0.02) and that seen in the clinically improving group (p=0.05) after exercise. We conclude that CSF-VEGF levels can increase after moderate exercise even in elderly hydrocephalus patients. This suggests that a potential benefit of exercise, especially in CSF drainage non-improved patients, may exist via a central VEGF mechanism. PMID:26498093

  19. CSF glucose test

    MedlinePlus

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 of the blood sugar level). Note: Normal value ranges may vary slightly ...

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

    PubMed

    Oberson, R

    1976-01-01

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

  1. Detecting polysaccharide antigen of Neisseria meningitidis group C in cerebrospinal fluid by dot-ELISA assay.

    PubMed

    Correia Barbosa, S F; Alkmin, M G; Landgraf, I M

    2000-06-01

    Cerebrospinal fluid (CSF) samples from 210 patients (200 with clinical evidence of bacterial meningitis, 10 with other clinical neurologic disease) were tested by a Dot-ELISA assay for detection of polysaccharide antigen of N. meningitidis group C. CSF samples were treated with EDTA 0.1 M, at pH 7.5 and heated to 90>C for 10 min. Polyclonal antiserum was purified by use of ethanol fractionation. The results were compared to those using bacterial culture (BC), latex agglutination (LA), counterimmunoelectrophoresis (CIE), and direct microscopy (DM) methods. Test results showed a correlation of 93.3%, 94.3%, 91.0% and 69.5% respectively, and sensitivity of 0.947 and specificity of 0.930. This study suggests that the dot-ELISA assay of CSF is a useful alternative technique for the diagnosis of group C meningitis. PMID:10934498

  2. Immunological studies of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination.

    PubMed

    Takahashi, Yukitoshi; Matsudaira, Takashi; Nakano, Hitoshi; Nasu, Hirosato; Ikeda, Hitoshi; Nakaoka, Kentaro; Takayama, Rumiko; Oota, Masayasu

    2016-09-15

    In 32 patients with prolonged central nervous system symptoms after human papillomavirus (HPV) vaccination, we measured conventional and immunological markers in cerebrospinal fluid (CSF) and compared with the levels in disease controls. Our studies revealed significantly decreased chloride and neuron-specific enolase (NSE) levels in CSF of patients with CNS symptoms after HPV vaccination compared to disease controls. IL-4, IL-13, and CD4(+) T cells increased significantly in patients, and IL-17 increased significantly from 12 to 24months after symptom onset. Chemokines (IL-8 and MCP-1) were also elevated, but CD8(+) T cells, PDGF-bb and IL-12 were reduced. Antibodies to GluN2B-NT2, GluN2B-CT and GluN1-NT increased significantly. These results suggest biological, mainly immunological, changes in the CSF of patients after HPV vaccination. PMID:27609278

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

    PubMed

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

    2015-01-01

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

  4. Cerebrospinal fluid profile and seroprevalence of antiganglioside reactivity in patients with neuralgic amyotrophy.

    PubMed

    Stich, Oliver; Glos, Daniela; Brendle, Marie; Dersch, Rick; Rauer, Sebastian

    2016-03-01

    Neuralgic amyotrophy (NA), also known as acute brachial plexitis, is postulated as an autoimmune pathogenesis. In a well-defined cohort of patients with NA, we analyzed the cerebrospinal fluid (CSF) profile and the prevalence of antiganglioside antibodies. Patients with Varicella zoster-associated radiculitis and healthy blood donors served as controls. An abnormal routine laboratory CSF profile was found in 29% of those with NA, mostly showing a disruption of the blood-brain barrier. Antibodies predominantly from the immunoglobulin M (IgM) isotype against at least one human ganglioside were detected in 36% of sera from patients with NA but in only 2% of controls. An NA-specific reactivity pattern was not detected, and there was no significant association with clinical or CSF parameters. This suggests that the seroprevalence of antiganglioside autoantibodies in patients with NA is nonspecific. PMID:26757215

  5. Enlarged cerebrospinal fluid spaces in opiate-dependent male patients: a stereological CT study.

    PubMed

    Danos, P; Van Roos, D; Kasper, S; Brömel, T; Broich, K; Krappel, C; Solymosi, L; Möller, H J

    1998-01-01

    Computed tomography was performed in 9 male patients with a diagnosis of opiate dependence and in 9 age-matched psychiatric controls (neurotic depression). Patients with a history or diagnosis of another substance dependence (alcohol, cocaine, cannabis) were excluded from the study. The volumes of internal and external components of cerebrospinal fluid (CSF) were measured with a point-counting stereological method. Analysis of variance with age as a covariate revealed a significant enlargement of external and external CSF spaces in male patients with opiate dependence. There was no significant correlation between the length of opiate dependence and the volumes of internal and external CSF spaces. The present results suggest that opiate dependence is associated with structural brain alterations. However, the relationship between opiate dependence and structural brain changes is complex and still not well understood. PMID:9732207

  6. 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. PMID:27284198

  7. 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.

  8. Determination of kynurenic acid in rat cerebrospinal fluid by HPLC with fluorescence detection.

    PubMed

    Bao, Ye; Luchetti, David; Schaeffer, Eric; Cutrone, Jingfang

    2016-01-01

    A sensitive HPLC method using fluorescence detection was developed to determine kynurenic acid (KYNA) level in rat cerebrospinal fluid (CSF). The method development was accomplished by screening different columns, optimizing zinc acetate concentration and determining the optimal HPLC flow rate. This method allowed direct injection of the CSF samples onto an Xselect C18 column and KYNA levels were measured fluorometrically by forming a fluorescent complex with zinc acetate that was delivered post-column. The limit of quantitation was 0.2 n m with 30 μL injection, corresponding to 6 fmol (signal-to-noise ratio = 10). The improved sensitivity enabled the measurement of KYNA in naive and drug-treated rat CSF. PMID:25963282

  9. 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.

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

    PubMed Central

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

    2015-01-01

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

  11. Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.

    PubMed

    Caruso, Donatella; Melis, Marta; Fenu, Giuseppe; Giatti, Silvia; Romano, Simone; Grimoldi, Maria; Crippa, Donatella; Marrosu, Maria Giovanna; Cavaletti, Guido; Melcangi, Roberto Cosimo

    2014-08-01

    Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis. PMID:24766130

  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. 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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    2016-05-01

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

  16. Low Cerebrospinal Fluid Amyloid-Beta Concentration Is Associated with Poorer Delayed Memory Recall in Women

    PubMed Central

    Haapalinna, Fanni; Paajanen, Teemu; Penttinen, Janne; Kokki, Hannu; Kokki, Merja; Koivisto, Anne M.; Hartikainen, Päivi; Solje, Eino; Hänninen, Tuomo; Remes, Anne Marja; Herukka, Sanna-Kaisa

    2016-01-01

    Background Data on the association of memory performance with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are inconsistent. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NB) is a commonly used validated cognitive tool; however, only few studies have examined its relationship with CSF biomarkers for AD. We studied the correlation of pathological changes in CSF biomarkers with various CERAD-NB subtests and total scores. Methods Out of 79 subjects (36 men, mean age 70.5 years), 63 had undergone an assessment of cognitive status with CERAD-NB and a CSF biomarker analysis due to a suspected memory disorder, and 16 were controls with no memory complaint. Results In women we found a significant correlation between CSF amyloid-beta (Aβ1-42) and several subtests measuring delayed recall. Word List Recall correlated with all markers: Aβ1-42 (r = 0.323, p = 0.035), tau (r = −0.304, p = 0.050) and hyperphosphorylated tau (r = −0.331, p = 0.046). No such correlations were found in men. Conclusions CSF biomarkers correlate with delayed memory scores in CERAD-NB in women, and women may have more actual AD pathology at the time of the investigations than men. PMID:27504119

  17. Unilateral Endoscopic Approach for Repair of Frontal Sinus Cerebrospinal Fluid Leak

    PubMed Central

    Roehm, Corrie E.; Brown, Seth M.

    2011-01-01

    Cerebrospinal fluid (CSF) leak closure remains one of the most difficult surgeries for skull base surgeons, particularly with frontal sinus involvement. Technological advances in endoscopic surgery increasingly allow for less morbid approaches to the frontal sinus. We describe a series of patients who underwent endoscopic frontal sinus CSF leak repair utilizing a unilateral approach, to evaluate the utility and outcomes of this method. We performed a retrospective review of four cases in tertiary care centers. Participants included patients with CSF leak involving the frontal sinus. Main outcome measures included cessation of CSF leak and frontal sinus patency. Three patients were closed on the first surgical attempt; one with a communicating hydrocephalus required a revision procedure. Leak etiologies included prior craniotomy for frontal sinus mucopyocele, spontaneous meningoencephalocele, erosion due to mucormycosis, and prior endoscopic sinus surgery. The frontal sinus remained patent in three of four patients. No patients have evidence of a leak at a minimum of 1 year after surgery. The repair of frontal sinus CSF leaks is possible in specific cases with an endoscopic unilateral approach in leaks with multiple etiologies. Surgeons should consider this approach when selecting the appropriate procedure for repair of frontal sinus CSF leaks. PMID:22451816

  18. Sandwich Wound Closure Reduces the Risk of Cerebrospinal Fluid Leaks in Posterior Fossa Surgery.

    PubMed

    Heymanns, Verena; Oseni, Abidemi W; Alyeldien, Ameer; Maslehaty, Homajoun; Parvin, Richard; Scholz, Martin; Petridis, Athanasios K

    2016-04-26

    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

  19. 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

  20. TLTF in Cerebrospinal Fluid for Detection and Staging of T. b. gambiense Infection

    PubMed Central

    Abdulla, Maha-Hamadien; Bakhiet, Moiz; Lejon, Veerle; Andersson, Jan; McKerrow, James; Al-Obeed, Omar; Harris, Robert A.

    2013-01-01

    Background Trypanosome-derived lymphocyte triggering factor (TLTF) is a molecule released by African trypanosomes that interacts with the host immune system, resulting in increased levels of IFN-γ production. Methodology/Principal findings TLTF and anti-TLTF antibodies were assessed in sera and cerebrospinal fluid (CSF) from patients infected with Trypanosoma brucei gambiense (T. b. gambiense) in an attempt to identify alternative markers for diagnosis and stage determination of human African trypanosomiasis or sleeping sickness. Seventy-four serum and sixty-one CSF samples from patients with parasitologically confirmed infection and known disease stage along with 13 sera and CSF from uninfected controls were tested. In serum the levels of anti-TLTF antibodies were unrelated to the disease stage. In contrast, levels of anti-TLTF antibodies in CSF were higher in intermediate/late stages than in early stage disease patients. Specificity of the detected antibodies was assessed by inhibition of TLTF bioactivity as represented by its ability to induce IFN-γ production. Additionally, TLTF was detected in CSF from late stage patients by Western blotting with the anti-TLTF specific monoclonal antibody MO3. Conclusions/Significance These findings suggest a new possibility for disease diagnosis with focus on involvement of the CNS through detection of TLTF and anti-TLTF antibodies in the CSF. PMID:24260185

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

    PubMed

    West, Wanda; Ehrmann, Jon; Johnson, Wendy

    2014-08-01

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

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

    PubMed

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

    2011-07-01

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

  3. CSF coccidioides complement fixation test

    MedlinePlus

    ... test that checks for infection due to the fungus Coccidioides in the cerebrospinal (CSF) fluid. This is ... Antibodies defend your body against bacteria, viruses, and fungi. If the antibodies are present, they stick, or " ...

  4. Repair and prevention of cerebrospinal fluid leakage in transsphenoidal surgery: a sphenoid sinus mucosa technique.

    PubMed

    Amano, Kosaku; Hori, Tomokatsu; Kawamata, Takakazu; Okada, Yoshikazu

    2016-01-01

    Cerebrospinal fluid (CSF) leakage is a common but sometimes serious complication after transsphenoidal surgery (TSS). To avoid this postsurgical complication, we usually repair the CSF leaking area using an autologous material, such as fat, fascia, or muscle graft and sometimes nasonasal septal flap. In this report, we propose a technique using a novel autologous material, sphenoid sinus mucosa (SSM), to repair intraoperative CSF leakage or prevent it postoperatively. On 26 February 2007, we introduced the technique of using SSM to repair or prevent CSF leakage in TSS. Until 30th of June 2014, we performed 500 TSSs for patients with pituitary or parasellar lesions. They were 195 men and 305 women with a mean age of 48.5 years (range, 5-85 years). We used SSM for patching or suturing the arachnoid laceration or dural defect, in lieu of fat or fascia harvested from abdomen or thigh, or made pedicle flap of SSM instead of nasonasal septal flap to cover the sellar floor. Comparing the previous 539 cases not using these techniques before 26 February 2007, intraoperative CSF leakage increased from 49 to 69.4% (p < 0.0001) due to more aggressive surgical technique, mainly related to more extensive approaches and lesion removals, but the rate of using fat was reduced significantly from 35.5 to 19.4% (p = 0.00021) in small or moderate CSF leaks during TSS without increasing the reoperation rate for postoperative CSF leaks (1.86 vs 1.2%, p = 0.45). The technique of using SSM to repair intraoperative CSF leaks or prevent them postoperatively in TSS was considered useful, effective, less invasive, easier for graft harvesting (same surgical field), and providing natural anatomical reconstruction, without potential donor site morbidity. We can recommend it as a standard method for CSF leaks repair and prevention in TSS. PMID:26338198

  5. Cerebrospinal fluid neuropeptide Y in combat veterans with and without posttraumatic stress disorder.

    PubMed

    Sah, Renu; Ekhator, Nosakhare N; Jefferson-Wilson, Lena; Horn, Paul S; Geracioti, Thomas D

    2014-02-01

    Accruing evidence indicates that neuropeptide Y (NPY), a peptide neurotransmitter, is a resilience-to-stress factor in humans. We previously reported reduced cerebrospinal fluid (CSF) NPY concentrations in combat-related posttraumatic stress disorder (PTSD) subjects as compared with healthy, non-combat-exposed volunteers. Here we report CSF NPY in combat-exposed veterans with and without PTSD. We quantified NPY concentrations in morning CSF from 11 male subjects with PTSD from combat in Iraq and/or Afghanistan and from 14 combat-exposed subjects without PTSD. NPY-like immunoreactivity (NPY-LI) was measured by EIA. The relationship between CSF NPY and clinical symptoms, as measured by the Clinician-Administered PTSD Scale (CAPS) and Beck Depression Inventory (BDI), was assessed, as was the relationship between combat exposure scale (CES) scores and CSF NPY. As compared with the combat-exposed comparison subjects without PTSD, individuals with PTSD had significantly lower concentrations of CSF NPY [mean CSF NPY was 258. 6 ± 21.64 pg/mL in the combat trauma-no PTSD group but only 180.5 ± 12.62 pg/mL in PTSD patients (p=0.008)]. After adjusting for CES and BDI scores the two groups were still significantly different with respect to NPY. Importantly, CSF NPY was negatively correlated with composite CAPS score and intrusive (re-experiencing) subscale scores, but did not significantly correlate with CES or BDI scores. Our current findings further suggest that NPY may regulate the manifestation of PTSD symptomatology, and extend previous observations of low CSF NPY concentrations in the disorder. Central nervous system NPY may be a clinically important pharmacotherapeutic target, and/or diagnostic measure, for PTSD. PMID:24485499

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

    PubMed

    Henriksen, Louise T; Nersting, Jacob; Raja, Raheel A; Frandsen, Thomas L; Rosthøj, Steen; Schrøder, Henrik; Albertsen, Birgitte K

    2014-07-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m(2) i.m. every second week, and to correlate CSF asparagine concentration with serum L-asparaginase enzyme activity. Danish children (1-17 years) with ALL, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, standard and intermediate risk, were included. CSF samples were obtained throughout L-asparaginase treatment at every scheduled lumbar puncture. A total of 128 samples from 31 patients were available for analysis. Median CSF asparagine concentration decreased from a pre-treatment level of 5·3 μmol/l to median levels ≤1·5 μmol/l. However, only 4/31 patients (five samples) had CSF asparagine concentrations below the limit of detection (0·1 μmol/l). In 11 patients, 24 paired same day serum and CSF samples were obtained. A decrease in CSF asparagine corresponded to serum enzyme activities above 50 iu/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000 iu/m(2) i.m. every second week effectively reduced CSF asparagine levels. PMID:24702187

  7. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain.

    PubMed

    Manda, Prashanth; Kushwaha, Avadhesh Singh; Kundu, Santanu; Shivakumar, H N; Jo, Seong Bong; Murthy, S Narasimha

    2016-02-28

    The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h(-1). The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h(-1) and 0.42±0.10h(-1) respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain. PMID:26732557

  8. A Sandwich Technique for Prevention of Cerebrospinal Fluid Rhinorrhea and Reconstruction of the Sellar Floor after Microsurgical Transsphenoidal Pituitary Surgery.

    PubMed

    Freyschlag, Christian F; Goerke, Stephanie Alice; Obernauer, Jochen; Kerschbaumer, Johannes; Thomé, Claudius; Seiz, Marcel

    2016-05-01

    Background Cerebrospinal fluid (CSF) leaks are a well-known complication of transsphenoidal surgery. Several autologous and artificial grafts have been used to close the sellar floor in an attempt to prevent postoperative CSF rhinorrhea. Objective To evaluate and describe a sandwich technique to close the sellar floor using autologous bone, absorbable gelatin sponge, and coated collagen fleece. Methods We reviewed 50 consecutive patients between April 2010 and August 2011 who underwent transsphenoidal surgery ending with reconstruction of the sellar floor with a particular sandwich technique. Patients with an intraoperative CSF leak received an additional lumbar drain. Results There were no cases of CSF rhinorrhea at postoperative follow-up after 6 weeks and no revision surgery. Conclusion The proposed sandwich technique for closure of the sellar floor to the sphenoid sinus is a suitable alternative to autologous grafts and seems to be effective in preventing CSF rhinorrhea. PMID:26091112

  9. Cerebrospinal fluid findings after epileptic seizures.

    PubMed

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

    2015-12-01

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

  10. The Influence of Body Position on Cerebrospinal Fluid Pressure Gradient and Movement in Cats with Normal and Impaired Craniospinal Communication

    PubMed Central

    Radoš, Milan; Erceg, Gorislav; Petošić, Antonio; Jurjević, Ivana

    2014-01-01

    Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension. PMID:24748150

  11. Therapeutic implications of the choroid plexus-cerebrospinal fluid interface in neuropsychiatric disorders.

    PubMed

    Demeestere, Delphine; Libert, Claude; Vandenbroucke, Roosmarijn E

    2015-11-01

    The choroid plexus (CP) comprises an epithelial monolayer that forms an important physical, enzymatic and immunologic barrier, called the blood-cerebrospinal fluid barrier (BCSFB). It is a highly vascularized organ located in the brain ventricles that is key in maintaining brain homeostasis as it produces cerebrospinal fluid (CSF) and has other important secretory functions. Furthermore, the CP-CSF interface plays a putative role in neurogenesis and has been implicated in neuropsychiatric diseases such as the neurodevelopmental disorders schizophrenia and autism. A role for this CNS border was also implicated in sleep disturbances and chronic and/or severe stress, which are risk factors for the development of neuropsychiatric conditions. Understanding the mechanisms by which disturbance of the homeostasis at the CP-CSF interface is involved in these different chronic low-grade inflammatory diseases can give new insights into therapeutic strategies. Hence, this review discusses the different roles that have been suggested so far for the CP in these neuropsychiatric disorders, with special attention to potential therapeutic applications. PMID:26116435

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status.

    PubMed

    Piccio, Laura; Deming, Yuetiva; Del-Águila, Jorge L; Ghezzi, Laura; Holtzman, David M; Fagan, Anne M; Fenoglio, Chiara; Galimberti, Daniela; Borroni, Barbara; Cruchaga, Carlos

    2016-06-01

    Low frequency coding variants in TREM2 are associated with increased Alzheimer disease (AD) risk, while loss of functions mutations in the gene lead to an autosomal recessive early-onset dementia, named Nasu-Hakola disease (NHD). TREM2 can be detected as a soluble protein in cerebrospinal fluid (CSF) and plasma, and its CSF levels are elevated in inflammatory CNS diseases. We measured soluble TREM2 (sTREM2) in the CSF of a large AD case-control dataset (n = 180) and 40 TREM2 risk variant carriers to determine whether CSF sTREM2 levels are associated with AD status or mutation status. We also performed genetic studies to identify genetic variants associated with CSF sTREM2 levels. CSF, but not plasma, sTREM2 was highly correlated with CSF total tau and phosphorylated-tau levels (r = 0.35, P < 1×10(-4); r = 0.40, P < 1×10(-4), respectively), but not with CSF Aβ42. AD cases presented higher CSF sTREM2 levels than controls (P = 0.01). Carriers of NHD-associated TREM2 variants presented significantly lower CSF sTREM2 levels, supporting the hypothesis that these mutations lead to reduced protein production/function (R136Q, D87N, Q33X or T66M; P = 1×10(-3)). In contrast, CSF sTREM2 levels were significantly higher in R47H carriers compared to non-carriers (P = 6×10(-3)), suggesting that this variant does not impact protein expression and increases AD risk through a different pathogenic mechanism than NHD variants. In GWAS analyses for CSF sTREM2 levels the most significant signal was located on the MS4A gene locus (P = 5.45 × 10(-07)) corresponding to one of the SNPs reported to be associated with AD risk in this locus. Furthermore, SNPs involved in pathways related to virus cellular entry and vesicular trafficking were overrepresented, suggesting that CSF sTREM2 levels could be an informative phenotype for AD. PMID:26754641

  16. [Assessment of prealbumin in cerebrospinal fluid].

    PubMed

    Hartmann, W; Kluge, H; Zahlten, W

    1987-03-01

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

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

    PubMed

    Schmidt, R M

    1979-01-01

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

  18. Spontaneous cerebrospinal fluid rhinorrhoea as the presenting feature of an invasive macroprolactinoma

    PubMed Central

    Mankia, Satveer Kaur; Weerakkody, Ruwan Alwis; Wijesuriya, Shanelle; Kandasamy, Narayanan; Finucane, Francis; Guilfoyle, Mathew; Antoun, Nagui; Pickard, John; Gurnell, Mark

    2009-01-01

    A 29-year-old male university student, with no prior history of trauma, presented with a 1 year history of clear fluid leaking intermittently from his left nostril. His past medical history included bilateral gynaecomastia since age 12, and recent low libido. β2-transferrin analysis of the nasal fluid confirmed a diagnosis of cerebrospinal fluid (CSF) rhinorrhoea. The serum prolactin was grossly elevated at 42 700 mU/l and brain magnetic resonance imaging (MRI) revealed a large parasellar/sellar mass. A diagnosis of invasive macroprolactinoma complicated by spontaneous CSF rhinorrhoea was made. The patient was commenced on treatment with cabergoline, but while awaiting surgery to repair the CSF leak he developed streptococcus mitis and sanguis meningitis. He made an uncomplicated recovery with antibiotic treatment. Immediately following this episode, the CSF rhinorrhoea resolved spontaneously. Subsequently, a repeat MRI scan revealed dramatic involution of the pituitary mass and the serum prolactin had fallen to 604 mU/l. PMID:21686345

  19. Spontaneous cerebrospinal fluid rhinorrhoea as the presenting feature of an invasive macroprolactinoma.

    PubMed

    Mankia, Satveer Kaur; Weerakkody, Ruwan Alwis; Wijesuriya, Shanelle; Kandasamy, Narayanan; Finucane, Francis; Guilfoyle, Mathew; Antoun, Nagui; Pickard, John; Gurnell, Mark

    2009-01-01

    A 29-year-old male university student, with no prior history of trauma, presented with a 1 year history of clear fluid leaking intermittently from his left nostril. His past medical history included bilateral gynaecomastia since age 12, and recent low libido. β2-transferrin analysis of the nasal fluid confirmed a diagnosis of cerebrospinal fluid (CSF) rhinorrhoea. The serum prolactin was grossly elevated at 42 700 mU/l and brain magnetic resonance imaging (MRI) revealed a large parasellar/sellar mass. A diagnosis of invasive macroprolactinoma complicated by spontaneous CSF rhinorrhoea was made. The patient was commenced on treatment with cabergoline, but while awaiting surgery to repair the CSF leak he developed streptococcus mitis and sanguis meningitis. He made an uncomplicated recovery with antibiotic treatment. Immediately following this episode, the CSF rhinorrhoea resolved spontaneously. Subsequently, a repeat MRI scan revealed dramatic involution of the pituitary mass and the serum prolactin had fallen to 604 mU/l. PMID:21686345

  20. Role of the RVM in Descending Pain Regulation Originating from the Cerebrospinal Fluid-Contacting Nucleus.

    PubMed

    Fei, Yan; Wang, Xin; Chen, Songsong; Zhou, Qiangqiang; Zhang, Chao; Li, Ying; Sun, Lihong; Zhang, Licai

    2016-07-01

    Evidence has suggested that cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) is correlated with the development and recurrence of pain. A recent research showed that the CSF-contacting nucleus acts as a component of the descending 5-hydroxytryptamine (5-HT) system and plays a role in descending pain inhibition. However, limited studies are conducted to investigate the relationship between the CSF-contacting nucleus and pain. In present study, we explored the effect of CSF-contacting nucleus on nociceptive behaviors in both normal and neuropathic rats via targeted ablation of the CSF-contacting nucleus in the brainstem, using cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. The CB-SAP-treated rats showed aggravated thermal hyperalgesia and mechanical allodynia. Also, results from immunohistochemical experiments showed that rostral ventromedial medulla (RVM) received fiber projection from the CSF-contacting nucleus, which disappeared after ablation of the CSF-contacting nucleus, and the CB-SAP treated rats showed downregulation of c-Fos expression in the RVM as compared with the rats receiving i.c.v. injection of phosphate buffer saline (PBS). A significant downregulation of 5-HT-labeled neurons and tryptophan hydroxylase 2 (TPH2) as the marker of 5-HT cells in the RVM, and 5-HT expression in spinal dorsal horn in both normal and chronic constriction injury (CCI) rats after i.c.v. injection of CB-SAP was observed. These results suggested that RVM may be involved in descending pain modulation originating from the CSF-contacting nucleus. PMID:26961890

  1. Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress.

    PubMed

    Wu, Yue-Hong; Song, Si-Yuan; Liu, He; Xing, Dan; Wang, Xin; Fei, Yan; Li, Guang-Ling; Zhang, Chao; Li, Ying; Zhang, Li-Cai

    2015-06-01

    The contribution of the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) and adrenomedullin (ADM) to the developmental modulation of stressful events remains controversial. This study explored the effects of endogenous ADM in the CSF-contacting nucleus on immobilization of stress-induced physiological parameter disorders and glucocorticoid hormone releasing hormone (CRH), rat plasma corticosterone expression, and verification of such effects by artificially lowering ADM expression in the CSF-contacting nucleus by targeted ablation of the nucleus. Immunohistochemical experiments showed that ADM-like immunoreactivity and the calcitonin receptor-like receptor (CRLR) marker were localized in the CSF-contacting nucleus. After 7 continuous days of chronic immobilization stress (CIS), animals exhibited anxiety-like behavior. Also, an increase in serum corticosterone, and enhanced expression of ADM in the CSF-contacting nucleus were observed, following activation by CIS. The intracerebroventricular (i.c.v.) administration of the ADM receptor antagonist AM22-52 significantly reduced ADM in the CSF-contacting nucleus, additionally, blocked the effects of ADM, meaning the expression of CRH in the hypothalamic paraventricular nucleus (Pa) and serum corticosterone level were increased, and the physiological parameters of the rats became correspondingly deteriorated. Additionally, the i.c.v. administration of cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to a cholera toxin subunit, completely eliminated the CSF-contacting nucleus, worsening the reaction of the body to CIS. The collective results demonstrated that ADM acted as a stress-related peptide in the CSF-contacting nucleus, and its lower expression and blocked effects in the nucleus contributed to the deterioration of stress-induced physiologic parameter disorders as well as the excessive expressions of stress-related hormones which were part of the hypothalamic-pituitary-adrenal (HPA) axis

  2. Receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid

    SciTech Connect

    Walsh, R.J.; Slaby, F.J.; Posner, B.I.

    1987-05-01

    Prolactin (PRL) interacts with areas of the central nervous system which reside behind the blood-brain barrier. While vascular PRL does not cross this barrier, it is readily accessible to the cerebrospinal fluid (CSF) from which it may gain access to the PRL-responsive areas of the brain. Studies were undertaken to characterize the mechanism responsible for the translocation of PRL from blood to CSF. Rats were given external jugular vein injections of (/sup 125/-I)iodo-PRL in the presence or absence of an excess of unlabeled ovine PRL (oPRL), human GH, bovine GH, or porcine insulin. CSF and choroid plexus were removed 60 min later. CSF samples were electrophoresed on sodium dodecyl sulfate-polyacrylamide slab gels and resultant autoradiographs were analyzed with quantitative microdensitometry. The data revealed that unlabeled lactogenic hormones, viz. oPRL and human GH, caused a statistically significant inhibition of (/sup 125/I)iodo-PRL transport from blood to CSF. In contrast, nonlactogenic hormones, viz bovine GH and insulin, had no effect on (/sup 125/I)iodo-PRL transport into the CSF. An identical pattern of competition was observed in the binding of hormone to the choroid plexus. Furthermore, vascular injections of (/sup 125/I)iodo-PRL administered with a range of concentrations of unlabeled oPRL revealed a dose-response inhibition in the transport of (/sup 125/I)iodo-PRL from blood to CSF. The study demonstrates that PRL enters the CSF by a specific, PRL receptor-mediated transport mechanism. The data is consistent with the hypothesis that the transport mechanism resides at the choroid plexus. The existence of this transport mechanism reflects the importance of the cerebroventricular system in PRL-brain interactions.

  3. The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord.

    PubMed

    Petracca, Yanina L; Sartoretti, Maria Micaela; Di Bella, Daniela J; Marin-Burgin, Antonia; Carcagno, Abel L; Schinder, Alejandro F; Lanuza, Guillermo M

    2016-03-01

    Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. PMID:26839365

  4. Blood and Cerebrospinal Fluid α-Tocopherol and Selenium Concentrations in Neonatal Foals with Neuroaxonal Dystrophy

    PubMed Central

    Finno, C.J.; Estell, K.E.; Katzman, S.; Winfield, L.; Rendahl, A.; Textor, J.; Bannasch, D.L.; Puschner, B.

    2016-01-01

    Background Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on α-tocopherol (α-TP)-deficient diet. Objective Intramuscular α-TP and selenium (Se) administration at 4 days of age would have no significant effect on serum or cerebrospinal fluid (CSF) α-TP in healthy foals. Serum and CSF α-TP, but not Se, would be significantly decreased in NAD/EDM-affected foals during first year of life. Animals Fourteen Quarter horse foals; 10 healthy foals supplemented with 0.02 mL/kg injectable α-TP and Se (n = 5) or saline (n = 5) at 4 days of age and 4 unsupplemented NAD/EDM-affected foals. Methods Complete neurologic examinations were performed, blood and CSF were collected before (4 days of age) and after supplementation at 10, 30, 60, 120, 180, 240, and 360 days of age. Additional blood collections occurred at 90, 150, 210, and 300 days. At 540 days, NAD/EDM-affected foals and 1 unsupplemented healthy foal were euthanized and necropsies performed. Results Significant decreases in blood, CSF α-TP and Se found in the first year of life in all foals, with most significant changes in serum α-TP from 4–150 days. Dam α-TP and Se significantly influenced blood concentrations in foals. Injection of α-TP and Se did not significantly increase CSF Se, blood or CSF α-TP in healthy foals. NAD/EDM-affected foals had significantly lower CSF α-TP through 120 days. Conclusions and Clinical Importance Injection of α-TP and Se at 4 days of age does not significantly increase blood or CSF α-TP. Despite all 14 foals remaining deficient in α-TP, only the 4 genetically predisposed foals developed NAD/EDM. PMID:26391904

  5. The value of multiparameter flow cytometry of cerebrospinal fluid involved by leukemia/lymphoma cells.

    PubMed

    Babusíková, O; Zelezníková, T

    2004-01-01

    The usefulness of multiparameter flow cytometric (FC) analysis of cerebrospinal fluid (CSF) was evaluated in leukemia/lymphoma patients having central nervous system (CNS) involvement of the disease. In 12 specimens of 8 patients with different types of leukemia/lymphoma (one case of T-ALL, 3 cases of early B-cell ALL, one case of AML, and 3 proven or suspicious NHL cases) the presence of pathological clone in CSF has been confirmed or excluded. The phenotypic patterns of CSF cells were defined according to those of bone marrow (BM)/peripheral blood (PB) at diagnosis or during follow-up of the same patients. Furthermore, in one case of suspicious CNS infiltration of NHL, the pathological clone was characterized as a highly suspicious of solid tumor and was proved to be a lung cancer metastasis. The definition was made on the basis of CD45 (common leukocyte antigen) and other studied CD markers negativity. The exact comparison of immunophenotypic profiles of specimens from different sites (CSF, BM, PB) of the same patient has been performed and no phenotypic changes were found. In some CSF specimens, where no cells of suspicious pathological clone were detected, in 4-color analysis only normal lymphocyte population was found even in small cell samples (even if the cellularity was < than 0.3x10-6). In these populations the high values of T-cells (CD3+) predominated and the high prevalence of CD4+ over CD8+ cells, and an almost total lack of B-lymphocytes was found. Our results suggest that positive CSF immunology is a useful indicator of malignancy and reflects leptomeningeal involvement. Simultaneously we demonstrated that FC analysis of CSF in the aim to detect possible CSF seeding of leukemia/lymphoma is a reliable and quick technique. PMID:15640938

  6. Modified Graded Repair of Cerebrospinal Fluid Leaks in Endoscopic Endonasal Transsphenoidal Surgery

    PubMed Central

    Park, Jae-Hyun; Choi, Jai Ho; Kim, Young-Il; Kim, Sung Won

    2015-01-01

    Objective Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time-consuming. Methods Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage. Results Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned. Conclusion Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en-bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks. PMID:26279811

  7. Differences in cerebrospinal fluid inflammatory cell reaction of patients with leptomeningeal involvement by lymphoma and carcinoma.

    PubMed

    Illán, Julia; Simo, Marta; Serrano, Cristina; Castañón, Susana; Gonzalo, Raquel; Martínez-García, María; Pardo, Javier; Gómez, Lidia; Navarro, Miguel; Altozano, Javier Pérez; Alvarez, Ruth; Bruna, Jordi; Subirá, Dolores

    2014-12-01

    Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and leptomeninges is a devastating complication in patients with epithelial cell neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous meningitis [LyM]). Information about the surrounding inflammatory cell populations is scarce. In this study, flow cytometry immunophenotyping was used to describe the distribution of the main leukocyte populations in the CSF of 83 patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These data were compared with those obtained in the CSF from 55 patients diagnosed with the same groups of neoplasia without meningeal involvement (solid tumors, n = 36; high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes, monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24% (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range, 70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No difference was observed between patients with breast adenocarcinoma (n = 30) and lung adenocarcinoma (n = 21), nor with different rates of malignant CSF involvement. Patients with lymphoma (with or without LyM) had a similar CSF leukocyte distribution, but cancer patients with LC and without LC had a distinctive PMN cell rate (P = 0.002). These data show that CSF samples from patients with LC have a greater number of inflammatory cells and a different leukocyte distribution than seen in the CSF from patients with LyM. Description of PMN cells is a distinctive parameter of patients with LC, compared with the CSF from patients with LyM and patients with cancer but without LC. PMID:24746871

  8. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. )); Stubbs, J.B. )

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  9. The transport of L-6-fluorodopa and its metabolites from blood to cerebrospinal fluid and brain.

    PubMed

    Hammerstad, J P; Pate, B D; Hewitt, K A; Chan, G L; Ruth, T J; Calne, D B

    1993-10-01

    The transport of L-6-fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of 18F-L-6-fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L-6-fluorodopa and its metabolites were determined in blood plasma and CSF by high-performance liquid chromatography. Raising the blood concentration of phenylalanine by intraperitoneal injection markedly reduced the accumulation of tracer in the brain. This indicates that L-6-fluorodopa and 3-O-methylfluorodopa, like native L-dopa and its O-methylated derivative, are transported at the brain capillary by the large neutral amino acid carrier-mediated system, which is subject to saturation and competition by other large neutral amino acids (such as phenylalanine) at physiological plasma concentrations. In contrast, administration of phenylalanine had no effect on the accumulation of tracer either in muscle, or as L-6-fluorodopa and 3-O-methylfluorodopa, in CSF. This suggests that the transport of L-dopa and its derivatives at the blood-CSF barrier differs from the transport at the blood-brain barrier and also that measurement of CSF L-dopa is not a good index of the transport and pharmacokinetics of L-dopa in the brain. However, the effect of phenylalanine administration in reducing the concentration of fluorohomovanillic acid in the CSF suggests that the concentration of homovanillic acid in the CSF is an accurate reflection of dopamine turnover in the brain. PMID:8215248

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

    PubMed

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

    2016-04-15

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

  11. 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia.

    PubMed

    Papassotiropoulos, A; Lütjohann, D; Bagli, M; Locatelli, S; Jessen, F; Buschfort, R; Ptok, U; Björkhem, I; von Bergmann, K; Heun, R

    2002-01-01

    The brain is the most cholesterol-rich organ in the human body. Accumulation of excess cholesterol in hippocampal neurons promotes the cleavage of the amyloid precursor protein (APP) into amyloidogenic components with the consequence of the acceleration of neuronal degeneration. Conversion of cholesterol to 24S-hydroxycholesterol mediated by cholesterol 24S-hydroxylase (CYP46) is the major pathway for the elimination of brain cholesterol and the maintenance of brain cholesterol homeostasis. We examined whether cerebrospinal fluid (CSF) 24S-hydroxycholesterol levels differ between patients with dementia, patients with mild cognitive impairment (MCI), and cognitively intact control subjects. Plasma and CSF concentrations of 24S-hydroxycholesterol and cholesterol in 32 patients with Alzheimer's disease (AD), 11 patients with vascular dementia, seven patients with MCI, and seven cognitively intact control subjects were measured by combined gas-chromatography/mass spectrometry. We show elevated concentrations of 24S-hydroxycholesterol in the CSF of AD patients and we interpret this finding as a consequence of increased cholesterol turnover in the central nervous system during neurodegeneration. The observed influence of the apolipoprotein E epsilon4 (APOE4) allele on CSF 24S-hydroxycholesterol concentrations with a gene-dosage effect suggests the existence of a link between the AD risk factor APOE4 and CNS cholesterol metabolism. The elevation of CSF 24S-hydroxycholesterol appears to occur early in the disease process, since patients with mild cognitive impairment had also increased CSF concentrations of this compound. We believe that the CSF concentration of 24S-hydroxycholesterol is altered in AD-related neurodegeneration and thus, CSF 24S-hydroxycholesterol may be a marker for monitoring the onset and progression of the disease. PMID:11755458

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

    PubMed

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

    2004-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces.

    PubMed

    Buishas, Joel; Gould, Ian G; Linninger, Andreas A

    2014-10-01

    Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 μL per mOsm in the ventricle and by 0.835 μL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema. PMID:25358881

  15. Cellular immune surveillance of central nervous system bypasses blood-brain barrier and blood-cerebrospinal-fluid barrier: revealed with the New Marburg cerebrospinal-fluid model in healthy humans.

    PubMed

    Kleine, Tilmann O

    2015-03-01

    In healthy human brain/spinal cord, blood capillaries and venules are locked differently with junctions and basement membrane (blood-brain barrier, blood-venule barrier). In choroid plexus, epithelial tight junctions and basement membrane lock blood-cerebrospinal-fluid (CSF) barrier. Lymphocytic cell data, quantified with multicolour flow-cytometry or immuno-cytochemical methods in sample pairs of lumbar CSF, ventrictricular CSF and peripheral venous blood, are taken from references; similarly, data of thoracic duct chyle and blood sample pairs. Through three circumventricular organs (median eminence, organum vasculosum lamina terminalis, area postrema), 15-30 μl blood are pressed by blood pressure through fenestrated capillaries, matrix/basement membrane spaces and ependyma cell lacks into ventricular/suboccipital CSF to generate CD3(+) , CD4(+) , CD8(+) , CD3(+) HLA-DR(+) , CD16(+) 56(+) 3(-) NK, CD19(+) 3(-) B subsets; some B, few NK cells adhere in circumventricular organs. Into lumbar CSF, 10-15 μl thoracic chyle with five lymphocyte subsets (without CD3(+) HLA-DR(+) cells) reflux, when CSF drains out with to-and-fro movements of chyle/CSF along nerve roots. Lymphocytes in lumbar CSF represent a mixture of blood and lymph lymphocytic cells with similar HLA-DR(+) CD3(+) cell counts in ventricular and lumbar CSF, higher CD3(+) , CD4(+) , CD8(+) subsets in lumbar CSF, and few NK and B cells due to absorption in circumventricular organs. The Marburg CSF Model reflects origin and turnover of lymphatic cells in CSF realistically; the model differs from ligand-multistep processes of activated lymphocytes through blood-brain-, blood-venule-, and blood-CSF-barriers; because transfer of inactivated native lymphocytes through the barriers is not found with healthy humans, although described so in literature. PMID:25641944

  16. Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF). Part III. In-vitro study of low flow velocity detection related to decreasing particle concentration (hematocrit) and tube lumen.

    PubMed

    Winkler, P; Helmke, K

    1992-01-01

    An in-vitro steady flow system was designed to determine the lowest flow velocities that can be detected by echographic colour flow imaging and spectral analysis. The flow detection level was determined hydrostatically by reducing the fluid level to below the point at which a flow signal was visible, then increasing the height until the colour flow reappeared. This was confirmed in all instances by spectral analysis. The height (angle-corrected velocity) of the spectral envelope was also determined. Mean volume flow was then obtained by using a graduated cylinder and a stop watch. The lowest hematocrit detectable was identified using a stepwise dilution of packed human red blood cells with 0.9% sodium chloride. Three different PVC-tubes with inner diameters of 2.1 mm, 1.1 mm and 0.51 mm were used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1594308

  17. Single Operation to Repair Multifocal Cerebrospinal Fluid Fistulae Following Gunshot Wound: A Case Report

    PubMed Central

    White-Dzuro, Gabrielle A.; Entezami, Pouya; Wanna, George; Russell, Paul; Chambless, Lola B.

    2016-01-01

    Introduction Traumatic cerebrospinal fluid (CSF) fistulae can be a challenging neurosurgical disease, often requiring complicated surgical intervention. Case Presentation A 54-year-old man presented with a gunshot wound to the head with complex injury to the skull base and significant CSF leakage from multiple sites. A single surgery was performed using a combined Neurosurgery, Neurotology, and Rhinology team, which was successful in repairing the multiple skull base defects and preventing further CSF leak. Discussion Trauma to the skull base is a common inciting factor for the development of CSF fistulae. Endoscopic approaches are often preferred for repairing these defects, but craniotomy remains a viable option that may be required in more complex cases. A combined approach has not been described previously, but was successful for this severe multifocal defect. Conclusion A multidisciplinary approach allowed for a combined intervention that addressed both the anterior and middle fossae fistulae simultaneously. This limited the potential infectious complications of continued CSF leak and allowed for early rehabilitation. PMID:27330926

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

    PubMed Central

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

    1999-01-01

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

  19. 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.

  20. 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

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

    PubMed

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

    2009-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. Cerebrospinal Fluid Neuropeptide Y Levels in Major Depression and Reported Childhood Trauma

    PubMed Central

    Soleimani, Laili; Oquendo, Maria A.; Sullivan, Gregory M.; Mathé, Aleksander A.

    2015-01-01

    Background: Neuropeptide Y (NPY) may enhance resilience to chronic stress. Low brain NPY reported in major depression may normalize in response to antidepressants. Methods: In this study, we examined the relationship of reported childhood trauma to cerebrospinal fluid (CSF) NPY–like immunoreactivity (NPY-LI) in 61 medication-free major depressive disorder (MDD) patients and 20 matched healthy volunteers. Results: Higher CSF NPY-LI was found in MDD compared to the healthy volunteer group (p = 0.01). A positive correlation of CSF NPY-LI with more adverse childhood trauma (p = 0.001) may be indicative of an intact but insufficient NPY-related stress response. Conclusions: We hypothesize that differences in published results may be explained by the existence of two groups of MDD in terms of CSF NPY levels: MDD with low CSF NPY prior to stress or in response to stress, and those with robust NPY responses to stress. Future studies should confirm the two groups and seek the molecular mechanism for their differences. PMID:25539507

  4. The role of cerebrospinal fluid pressure in glaucoma pathophysiology: the dark side of the optic disc.

    PubMed

    Morgan, William H; Yu, Dao Yi; Balaratnasingam, Chandrakumar

    2008-08-01

    It is generally accepted that glaucoma occurs when intraocular pressure (IOP) is raised above atmospheric pressure beyond tolerable limits for the optic disc. However, the other, unseen side of the optic disc is not air but a set of pressure compartments dominated by the cerebrospinal fluid (CSF) within the subarachnoid space. This invisibility has made investigation difficult; however, in recent decades there has been increased interest in this corollary to IOP. We briefly review the anatomy of the optic nerve subarachnoid space and its pressure relationships to intracranial, retrolaminar, and orbital tissue pressures. The CSF pressure is equivalent to IOP in its influence on translaminar pressure gradient and optic disk surface movement. At low CSF pressure, its influence on retrolaminar tissue pressure is reduced tending to minimize an increase in translaminar pressure gradient. The available evidence suggests that orbital tissue pressure provides this moderating influence. CSF pressure affects axonal transport, which is known to be important in glaucoma etiology and retinal venous outflow and pressures. Recent attempts to develop noninvasive measurement of CSF pressure have increased our knowledge of retinal venous changes in glaucoma. Further work in this area is likely to greatly increase our understanding of glaucoma. PMID:18703953

  5. Systemic Pharmacokinetics and Cerebrospinal Fluid Uptake of Intravenous Ceftriaxone in Patients with Amyotrophic Lateral Sclerosis

    PubMed Central

    Zhao, Yanli; Cudkowicz, Merit E.; Shefner, Jeremy; Krivickas, Lisa; David, William S.; Vriesendorp, Francine; Pestronk, Alan; Caress, James B.; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Harmatz, Jerold S.; Schoenfeld, David; Greenblatt, David J

    2015-01-01

    The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS). The pharmacokinetics (PK) of ceftriaxone in plasma and cerebrospinal fluid (CSF) were investigated in 66 participants in a previously reported clinical trial. Their mean age was 51 years, and 65 % were male. Participants were randomly assigned to one of three treatment groups receiving intravenous infusions (mean duration: 25 minutes) every 12 hours of either: placebo and placebo; 2 grams ceftriaxone and placebo; or 2 grams ceftriaxone twice. Mean steady-state plasma PK variables were: volume of distribution, 14 liters (0.17 liters/kg); elimination half-life, 8 - 9 hours; total clearance, 17-21 mL/min (0.22 - 0.25 mL/min/kg). Values were not different between dosage groups. CSF PK analysis, determined through sparse CSF sampling, indicated apparent entry and elimination half-life values of 1.0 and 34 hours, respectively. With both dosage regimens, CSF concentrations were maintained above the target threshold of 1.0 μM (0.55 μg/mL) as determined from in vitro models. The plasma and CSF PK profile of ceftriaxone were used as a basis for planning the Phase 3 clinical trial of ceftriaxone in ALS. PMID:24771634

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

    PubMed Central

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

    2015-01-01

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

  7. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    PubMed

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-γ concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-γ may be associated with EV71-induced neuropathology. PMID:25611005

  8. Mechanism for measurement of flow rate of cerebrospinal fluid in hydrocephalus shunts.

    PubMed

    Rajasekaran, Sathish; Kovar, Spencer; Qu, Peng; Inwald, David; Williams, Evan; Qu, Hongwei; Zakalik, Karol

    2014-01-01

    The measurement of the flow rate of cerebrospinal fluid (CSF) or existence of CSF flow inside the shunt tube after shunt implant have been reported as tedious process for both patients and doctors; this paper outlines a potential in vitro flow rate measurement method for CSF in the hydrocephalus shunt. The use of implantable titanium elements in the shunt has been proposed to allow for an accurate temperature measurement along the shunt for prediction of CSF flow rate. The CSF flow velocity can be deduced by decoupling the thermal transfer in the measured differential time at a pair of measurement spots of the titanium elements. Finite element analyses on the fluidic and thermal behaviors of the shunt system have been conducted. Preliminary bench-top measurements on a simulated system have been carried out. The measured flow rates, ranging from 0.5 mm/sec to 1.0 mm/sec, which is clinically practical, demonstrate good agreements with the simulation results. PMID:25570411

  9. 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

  10. Cerebrospinal Fluid Aβ40 Improves the Interpretation of Aβ42 Concentration for Diagnosing Alzheimer’s Disease

    PubMed Central

    Dorey, Aline; Perret-Liaudet, Armand; Tholance, Yannick; Fourier, Anthony; Quadrio, Isabelle

    2015-01-01

    The combination of decreased amyloid β42 (Aβ42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer’s disease (AD). Previous studies showed significant heterogeneity in CSF Aβ42 levels to discriminate AD from non-AD patients. It was also suggested that the CSF amyloid peptide β42/β40 ratio has better diagnostic performance than Aβ42 alone. The objective of the present study was to investigate the potential added value of determining CSF amyloid β40 peptide (Aβ40) for biological diagnosis of AD when CSF Aβ42 levels failed. CSF AD biomarkers were run in 2,171 samples from 1,499 AD and 672 non-AD patients. The following pathologic thresholds were used to define an AD-positive CSF biomarker profile: T-Tau ≥ 400 ng/L, P-Tau181 ≥ 60 ng/L, and Aβ42 ≤ 700 ng/L. CSF Aβ40 was assayed in AD patients with CSF Aβ42 levels above 700 ng/L and non-AD patients with CSF Aβ42 levels below 700 ng/L. CSF Aβ40 levels were higher in AD than non-AD patients. The receiver operator characteristic curves of CSF Aβ40 and the Aβ42/Aβ40 ratio defined AD cut-off values at 12,644 ng/L and 0.06, respectively. In AD patients with non-pathological CSF Aβ42, CSF Aβ40 concentration was able to correct 76.2% of cases when expressed as CSF Aβ42/Aβ40 ratio and 94.7% of cases when used alone. Using CSF Aβ42 and then CSF Aβ40, the percentage of misinterpreted AD patients fell to 1.0%. CSF Aβ40 concentration improved interpretation of Aβ42 level for the diagnosis of AD. CSF Aβ40 alone showed better diagnostic performance than the amyloid peptide Aβ42/Aβ40 ratio. The added value of determining CSF Aβ40 in AD diagnosis now needs confirming in a cohort of definite AD patients and to be completed with novel amyloid cascade biomarkers. PMID:26640457

  11. Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of dairy cows.

    PubMed

    Laeger, T; Görs, S; Metges, C C; Kuhla, B

    2012-03-01

    Endocrines and metabolites in the circulation act as long-term hunger or satiety signals in the brain during negative energy balance and play an important role in the control of feed intake. These signals also occur in the cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem: 2 major centers of feed intake regulation. Thus CSF functions as a transport medium for fuel signals between blood and brain. The CSF metabolite concentrations are mainly under control of the blood-brain barriers, which provide specific carrier molecules facilitating the entry of substances required by the brain and protect the brain from factors that could impair neuronal function. The transport of small molecules such as amino acids (AA) across the blood-brain barriers may be limited by competing AA that share a common transporter for the uptake into brain. Consequently, CSF metabolite concentrations differ from those in blood. Thus it appears likely that central (CSF) rather than peripheral (blood) metabolites act as pivotal signals for the control of feed intake. However, the contribution of putative orexigenic and anorexigenic signals in CSF of cows has not been studied so far. Therefore, the aim of this study was to elucidate associations existing between both plasma and CSF metabolites, each in response to feed restriction-induced negative energy balance. Seven German Holstein dairy cows, between 87 and 96 DIM of the second lactation (milk yield, 27.9 L/d) were fed ad libitum (AL) for 4 d and CSF from the spinal cord and blood from the jugular vein was withdrawn before morning feeding at the fifth day. Subsequently, animals were feed restricted (R) to 50% of the previous AL intake for 4 d and CSF and plasma were collected at the ninth day. Body weight, feed intake, water intake, and milk production were determined. Thirty-one AA, β-hydroxybutyric acid, cholesterol, glucose, lactate, nonesterified fatty acids, urea, and osmolality were measured in both CSF and

  12. 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

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

    PubMed Central

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

    2014-01-01

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

  14. 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

  15. 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

  16. 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.

  17. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  18. Cerebrospinal fluid volume measurements in hydrocephalic rats.

    PubMed

    Basati, Sukhraaj; Desai, Bhargav; Alaraj, Ali; Charbel, Fady; Linninger, Andreas

    2012-10-01

    Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic

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

    PubMed

    Thomas, Anitha Ann; Goh, Felicia Tze Yee

    2013-01-01

    Presence of bone marrow elements in cerebrospinal fluid is rare. Journal publications on this topic are few and majority of them were written over a decade ago mostly as case reports in young children or the elderly. The increased cellularity and presence of myeloid precursors can be a pitfall and may be misdiagnosed as leukemia or lymphoma or central nervous system infection, when the specimen is actually not representative. With the intention to create awareness of potential pitfalls and avoid erroneous diagnoses, as well as adding on to the current photo archive of bone marrow elements in CSF, we present a recent case of bone marrow contaminants in the CSF of a 16-year-old girl. PMID:24228067

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

    PubMed

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

    1998-06-12

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2012-01-01

    Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus (CP), the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF). Enlarged brain ventricles are already present at the time of disease onset (young adulthood) and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that altered CP/CSF dynamics during neurodevelopment may be considered a risk, causative and/or participating factor for development of schizophrenia. PMID:22891052

  3. 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

  4. Beta-endorphin, somatostatin, and prolactin levels in cerebrospinal fluid of epileptic patients after generalised convulsion.

    PubMed Central

    Pitkänen, A; Jolkkonen, J; Riekkinen, P

    1987-01-01

    The possible role of different peptidergic systems in the postictal stage of human epilepsy was studied by measuring beta-endorphin, somatostatin, and prolactin levels by radioimmunoassay of cerebrospinal fluid (CSF) from nine epileptic patients. The first sample was taken within 2 hours after generalised tonic-clonic convulsion, and the second sample was obtained interictally after 1-4 days without any kind of clinically observable seizures. beta-endorphin was elevated postictally (p = 0.044) compared with interictal levels. SLI and PROL were similar in both samples. The present study suggests that in humans beta-endorphin is released into CSF during generalised seizures. This may indicate that neurons containing beta-endorphin are activated during a seizure. PMID:2890716

  5. Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid.

    PubMed

    Schläger, Christian; Körner, Henrike; Krueger, Martin; Vidoli, Stefano; Haberl, Michael; Mielke, Dorothee; Brylla, Elke; Issekutz, Thomas; Cabañas, Carlos; Nelson, Peter J; Ziemssen, Tjalf; Rohde, Veit; Bechmann, Ingo; Lodygin, Dmitri; Odoardi, Francesca; Flügel, Alexander

    2016-02-18

    In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue. How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical. Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen

  6. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma.

    PubMed

    Baraniskin, Alexander; Kuhnhenn, Jan; Schlegel, Uwe; Maghnouj, Abdelouahid; Zöllner, Hannah; Schmiegel, Wolf; Hahn, Stephan; Schroers, Roland

    2012-01-01

    Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma. The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers. With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver-operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma. In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas. PMID:21937590

  7. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma

    PubMed Central

    Baraniskin, Alexander; Kuhnhenn, Jan; Schlegel, Uwe; Maghnouj, Abdelouahid; Zöllner, Hannah; Schmiegel, Wolf; Hahn, Stephan; Schroers, Roland

    2012-01-01

    Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma. The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers. With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver-operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma. In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas. PMID:21937590

  8. Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis.

    PubMed

    Rolfes, Melissa A; Rhein, Joshua; Schutz, Charlotte; Taseera, Kabanda; Nabeta, Henry W; Huppler Hullsiek, Kathy; Akampuira, Andrew; Rajasingham, Radha; Musubire, Abdu; Williams, Darlisha A; Thienemann, Friedrich; Bohjanen, Paul R; Muzoora, Conrad; Meintjes, Graeme; Meya, David B; Boulware, David R

    2015-12-01

    Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%-50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7-1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by "enhanced consolidation" therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1-2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6-2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes. PMID:26716103

  9. Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

    PubMed Central

    Hwang, Janice J.; Johnson, Andrea; Cline, Gary; Belfort-DeAguiar, Renata; Snegovskikh, Denis; Khokhar, Babar; Han, Christina S.; Sherwin, Robert S.

    2015-01-01

    Background Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose. Methods In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section. Results As expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups. Conclusions These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption. PMID:26035307

  10. Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis.

    PubMed Central

    Karlsson, M; Hammers, S; Nilsson-Ehle, I; Malmborg, A S; Wretlind, B

    1996-01-01

    Concentrations of doxycycline and penicillin G in serum and cerebrospinal fluid (CSF) were analyzed in 46 patients during treatment for neuroborreliosis. Twenty patients were treated intravenously with penicillin G at 3 g every 6 h (q6h), and 26 patients were treated orally with doxycycline at 200 mg q24h. All samples were collected on day 13 of treatment. The median concentrations of penicillin G in serum were 0.5, 37, and 5.6 micrograms/ml before and 1 and 3 h after drug administration, and that in CSF was 0.5 (range, 0.3 to 1.6) microgram/ml after 2 to 3 h. The median concentrations of doxycycline in serum were 2.1, 6.1, and 4.7 micrograms/ml before and 2 and 6 h after drug administration, and that in CSF was 0.6 (range, 0.4 to 2.5) microgram/ml after 4 h. All patients had concentrations of penicillin G or doxycycline in CSF above the lowest reported MICs of penicillin G (0.003 microgram/ml) and doxycycline (0.12 microgram/ml) for Borrelia burgdorferi. However, no patients had a drug concentration in CSF above the highest reported MIC of penicillin G (8 micrograms/ml), and only one had a drug concentration in CSF above the highest reported MIC of doxycycline (2 micrograms/ml), despite good clinical response to treatment. No treatment failure or relapse was observed during a 1-year follow-up, although one patient treated with penicillin G and one treated with doxycycline were retreated because of residual pain. The chosen dosages of penicillin G and doxycycline seem to give sufficient concentrations in serum and CSF for the treatment of neuroborreliosis. PMID:8723448

  11. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.

    PubMed

    Mulder, Sandra D; van der Flier, Wiesje M; Verheijen, Jan H; Mulder, Cees; Scheltens, Philip; Blankenstein, Marinus A; Hack, C Erik; Veerhuis, Robert

    2010-01-01

    Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain. PMID:20164582

  12. Incorporating and Compensating Cerebrospinal Fluid in Surface-Based Forward Models of Magneto- and Electroencephalography

    PubMed Central

    Stenroos, Matti; Nummenmaa, Aapo

    2016-01-01

    MEG/EEG source imaging is usually done using a three-shell (3-S) or a simpler head model. Such models omit cerebrospinal fluid (CSF) that strongly affects the volume currents. We present a four-compartment (4-C) boundary-element (BEM) model that incorporates the CSF and is computationally efficient and straightforward to build using freely available software. We propose a way for compensating the omission of CSF by decreasing the skull conductivity of the 3-S model, and study the robustness of the 4-C and 3-S models to errors in skull conductivity. We generated dense boundary meshes using MRI datasets and automated SimNIBS pipeline. Then, we built a dense 4-C reference model using Galerkin BEM, and 4-C and 3-S test models using coarser meshes and both Galerkin and collocation BEMs. We compared field topographies of cortical sources, applying various skull conductivities and fitting conductivities that minimized the relative error in 4-C and 3-S models. When the CSF was left out from the EEG model, our compensated, unbiased approach improved the accuracy of the 3-S model considerably compared to the conventional approach, where CSF is neglected without any compensation (mean relative error < 20% vs. > 40%). The error due to the omission of CSF was of the same order in MEG and compensated EEG. EEG has, however, large overall error due to uncertain skull conductivity. Our results show that a realistic 4-C MEG/EEG model can be implemented using standard tools and basic BEM, without excessive workload or computational burden. If the CSF is omitted, compensated skull conductivity should be used in EEG. PMID:27472278

  13. Routine Testing for Anaerobic Bacteria in Cerebrospinal Fluid Cultures Improves Recovery of Clinically Significant Pathogens

    PubMed Central

    Pittman, Meredith E.; Thomas, Benjamin S.; Wallace, Meghan A.; Weber, Carol J.

    2014-01-01

    In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens. PMID:24622102

  14. Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

    PubMed Central

    Rolfes, Melissa A.; Rhein, Joshua; Schutz, Charlotte; Taseera, Kabanda; Nabeta, Henry W.; Huppler Hullsiek, Kathy; Akampuira, Andrew; Rajasingham, Radha; Musubire, Abdu; Williams, Darlisha A.; Thienemann, Friedrich; Bohjanen, Paul R.; Muzoora, Conrad; Meintjes, Graeme; Meya, David B.; Boulware, David R.

    2015-01-01

    Background. Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods. Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results. Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions. Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes. PMID:26716103

  15. Cerebrospinal fluid Aβ40 is similarly reduced in patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease.

    PubMed

    Baldeiras, Inês; Santana, Isabel; Leitão, Maria João; Ribeiro, Maria Helena; Pascoal, Rui; Duro, Diana; Lemos, Raquel; Santiago, Beatriz; Almeida, Maria Rosário; Oliveira, Catarina Resende

    2015-11-15

    Cerebrospinal fluid (CSF) biomarkers have been increasingly studied for dementia diagnosis, however the accuracy to distinguish between different forms of dementia is still unsatisfactory. In this study, the added value of another CSF Aβ-peptide (Aβ40), along with the core CSF markers t-Tau, p-Tau, and Aβ42, in the discrimination between two large dementia groups of Frontotemporal Lobar Degeneration (FTLD; n=107), Alzheimer's Disease (AD; n=107) and non-demented subjects (n=33) was evaluated. In FTLD, t-Tau and p-Tau were significantly increased in relation to controls, but lower than in AD, while Aβ42 was similar in FTLD and controls, but higher than in AD. Equally reduced Aβ40 levels were seen in both dementia groups, and therefore the combination of Aβ40 with core CSF biomarkers optimally discriminated FTLD and AD patients from controls. Aβ42 and t-Tau were selected as the best biomarker subset to differentiate FTLD from AD, with no added value of Aβ40 to the model. Diagnostic accuracy between FTLD and AD was still sub-optimal, with a significant percentage (23%) of FTLD patients, in particularly women, carrying an ApoE-ε4 allele, showing a CSF-AD biomarkers profile. Although CSF Aβ40 does not appear to have an additional value in the distinction between FTLD and AD, it increases the discrimination between subjects with dementia from controls. A CSF-AD biomarker profile can be seen in patients with a clinical phenotype of FTLD, reinforcing the need for autopsy confirmation. PMID:26388316

  16. Incorporating and Compensating Cerebrospinal Fluid in Surface-Based Forward Models of Magneto- and Electroencephalography.

    PubMed

    Stenroos, Matti; Nummenmaa, Aapo

    2016-01-01

    MEG/EEG source imaging is usually done using a three-shell (3-S) or a simpler head model. Such models omit cerebrospinal fluid (CSF) that strongly affects the volume currents. We present a four-compartment (4-C) boundary-element (BEM) model that incorporates the CSF and is computationally efficient and straightforward to build using freely available software. We propose a way for compensating the omission of CSF by decreasing the skull conductivity of the 3-S model, and study the robustness of the 4-C and 3-S models to errors in skull conductivity. We generated dense boundary meshes using MRI datasets and automated SimNIBS pipeline. Then, we built a dense 4-C reference model using Galerkin BEM, and 4-C and 3-S test models using coarser meshes and both Galerkin and collocation BEMs. We compared field topographies of cortical sources, applying various skull conductivities and fitting conductivities that minimized the relative error in 4-C and 3-S models. When the CSF was left out from the EEG model, our compensated, unbiased approach improved the accuracy of the 3-S model considerably compared to the conventional approach, where CSF is neglected without any compensation (mean relative error < 20% vs. > 40%). The error due to the omission of CSF was of the same order in MEG and compensated EEG. EEG has, however, large overall error due to uncertain skull conductivity. Our results show that a realistic 4-C MEG/EEG model can be implemented using standard tools and basic BEM, without excessive workload or computational burden. If the CSF is omitted, compensated skull conductivity should be used in EEG. PMID:27472278

  17. Modern cerebrospinal fluid analyses for the diagnosis of diffuse large B-cell lymphoma of the CNS.

    PubMed

    Baraniskin, Alexander; Schroers, Roland

    2014-01-01

    CNS lymphomas represent rare and aggressive variants of extranodal non-Hodgkin's lymphomas, which may present with diverse neurological symptoms and are often diagnostically challenging. Primary CNS lymphomas develop within the CNS and characteristically involve the brain, leptomeninges, eyes and, in rare cases, spinal cord. Secondary CNS lymphomas are characterized by expansion of systemic lymphomas to the CNS. Multimodal investigation of cerebrospinal fluid (CSF) comprises an important component of the diagnostic work-up for patients with suspected CNS lymphomas. Cytopathological examination of the CSF is still regarded as the 'gold standard' for the diagnosis of leptomeningeal malignant disease. However, cytopathology has only a low sensitivity in detecting leptomeningeal lymphoma involvement. Modern technologies including proteochemical and immunophenotypic studies by flow cytometry, and molecular genetic analyses of CSF may increase sensitivity and specificity, therefore, facilitating the diagnosis of CNS lymphomas. This review gives an overview and discussion of the current aspects of CSF analyses in CNS lymphomas. PMID:25054902

  18. Bioanalytical method development and validation for the determination of glycine in human cerebrospinal fluid by ion-pair reversed-phase liquid chromatography-tandem mass spectrometry.

    PubMed

    Jiang, Jian; James, Christopher A; Wong, Philip

    2016-09-01

    A LC-MS/MS method has been developed and validated for the determination of glycine in human cerebrospinal fluid (CSF). The validated method used artificial cerebrospinal fluid as a surrogate matrix for calibration standards. The calibration curve range for the assay was 100-10,000ng/mL and (13)C2, (15)N-glycine was used as an internal standard (IS). Pre-validation experiments were performed to demonstrate parallelism with surrogate matrix and standard addition methods. The mean endogenous glycine concentration in a pooled human CSF determined on three days by using artificial CSF as a surrogate matrix and the method of standard addition was found to be 748±30.6 and 768±18.1ng/mL, respectively. A percentage difference of -2.6% indicated that artificial CSF could be used as a surrogate calibration matrix for the determination of glycine in human CSF. Quality control (QC) samples, except the lower limit of quantitation (LLOQ) QC and low QC samples, were prepared by spiking glycine into aliquots of pooled human CSF sample. The low QC sample was prepared from a separate pooled human CSF sample containing low endogenous glycine concentrations, while the LLOQ QC sample was prepared in artificial CSF. Standard addition was used extensively to evaluate matrix effects during validation. The validated method was used to determine the endogenous glycine concentrations in human CSF samples. Incurred sample reanalysis demonstrated reproducibility of the method. PMID:27262106

  19. Invader plus method detects herpes simplex virus in cerebrospinal fluid and simultaneously differentiates types 1 and 2.

    PubMed

    Allawi, Hatim T; Li, Haijing; Sander, Tamara; Aslanukov, Azamat; Lyamichev, Victor I; Blackman, Amondrea; Elagin, Slava; Tang, Yi-Wei

    2006-09-01

    We report here on the development and validation of a prototype Invader Plus method for the qualitative detection of herpes simplex virus types 1 and 2 in cerebrospinal fluid (CSF). The method combines PCR and Invader techniques in a single, closed-tube, continuous-reaction format that gives an analytical sensitivity of approximately 10 copies per reaction. The clinical sensitivity and specificity were 100.0% and 98.6%, respectively, when the results of the method were validated against the results obtained with a PCR colorimetric microtiter plate system by use of clinical CSF specimens. PMID:16954297

  20. Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline.

    PubMed

    Comi, Cristoforo; Carecchio, Miryam; Chiocchetti, Annalisa; Nicola, Stefania; Galimberti, Daniela; Fenoglio, Chiara; Cappellano, Giuseppe; Monaco, Francesco; Scarpini, Elio; Dianzani, Umberto

    2010-01-01

    Inflammation is believed to play a role in Alzheimer's disease (AD). Osteopontin (OPN) is a molecule involved in macrophage recruitment and activation and implicated in neurodegeneration. In order to elucidate the role of OPN in AD, we evaluated its levels in serum and cerebrospinal fluid (CSF) of 67 AD patients, 46 frontotemporal dementia (FTD) patients, and 69 controls. We found that OPN levels: i) are significantly increased in the CSF of AD patients; ii) correlate with MMSE score; and iii) are higher in the early disease phases ( 2 years). These findings support a role of OPN in AD pathogenesis. PMID:20308780

  1. Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients.

    PubMed

    Wu, Wei; Guan, Yi; Zhao, Gang; Fu, Xi-Jia; Guo, Tie-Zhu; Liu, Yue-Ting; Ren, Xin-Liang; Wang, Wei; Liu, Han-Rui; Li, Yun-Qian

    2016-07-01

    The present study investigated the correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in cerebrospinal fluid (CSF) and subarachnoid hemorrhage (SAH) progression. A meta-analysis was further conducted from pooled data to analyze the clinical value of IL-6 and TNF-α in SAH diagnosis. In our case-control study, a total of 57 SAH patients were assigned to two groups, CVS group (n = 27) and non-CVS group (n = 30), based on the presence of cerebral vasospasm (CVS). In addition, 65 healthy subjects were enrolled as controls. IL-6 and TNF-α levels in CSF were measured in all the study subjects by enzyme-linked immunosorbent assay (ELISA). For meta-analysis, an exhaustive literature search was conducted to identify relevant published articles and strict inclusion and exclusion criteria were applied to select studies for the present meta-analysis. Data extracted from these studies was analyzed using STATA 12.0 software. IL-6 and TNF-α levels in CSF of SAH patients were markedly higher than those of healthy controls (all P < 0.001). Further, CVS patients showed elevated IL-6 and TNF-α levels in CSF compared to non-CVS patients (all P < 0.001). The increase in IL-6 and TNF-α levels in CSF correlated with the increasing disease severity, based on Hunt-Hess grade, in SAH patients (all P < 0.05). Our meta-analysis also confirmed that IL-6 and TNF-α CSF levels were markedly higher in SAH patients compared to healthy controls (all P < 0.001). Ethnicity-stratified analysis showed that both IL-6 and TNF-α CSF levels were elevated in Asian SAH patients, compared to their healthy counterparts (all P < 0.05). The TNF-α CSF levels were significantly higher in Caucasian SAH patients (P < 0.001), but the IL-6 CSF levels showed no such differences compared to the healthy controls (P = 0.219). Subgroup analysis based on the presence of CVS showed that both IL-6 and TNF-α CSF levels were markedly higher in CVS

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

    PubMed

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

    2015-09-01

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

  3. 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. PMID:26610766

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

    PubMed

    Saratsis, Amanda M; Yadavilli, Sridevi; Magge, Suresh; Rood, Brian R; Perez, Jennifer; Hill, D Ashley; Hwang, Eugene; Kilburn, Lindsay; Packer, Roger J; Nazarian, Javad

    2012-05-01

    Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor-related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids--such as cerebrospinal fluid (CSF), serum, and urine--can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG. PMID:22492959

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

    PubMed

    Khan, Tapan K; Alkon, Daniel L

    2015-01-01

    Widely researched Alzheimer's disease (AD) biomarkers include in vivo brain imaging with PET and MRI, imaging of amyloid plaques, and biochemical assays of Aβ 1 - 42, total tau, and phosphorylated tau (p-tau-181) in cerebrospinal fluid (CSF). In this review, we critically evaluate these biomarkers and discuss their clinical utility for the differential diagnosis of AD. Current AD biomarker tests are either highly invasive (requiring CSF collection) or expensive and labor-intensive (neuroimaging), making them unsuitable for use in the primary care, clinical office-based setting, or to assess drug efficacy in clinical trials. In addition, CSF and neuroimaging biomarkers continue to face challenges in achieving required sensitivity and specificity and minimizing center-to-center variability (for CSF-Aβ 1 - 42 biomarkers CV = 26.5% ; http://www.alzforum.org/news/conference-coverage/paris-standardization-hurdle-spinal-fluid-imaging-markers). Although potentially useful for selecting patient populations for inclusion in AD clinical trials, the utility of CSF biomarkers and neuroimaging techniques as surrogate endpoints of drug efficacy needs to be validated. Recent trials of β- and γ-secretase inhibitors and Aβ immunization-based therapies in AD showed no significant cognitive improvements, despite changes in CSF and neuroimaging biomarkers. As we learn more about the dysfunctional cellular and molecular signaling processes that occur in AD, and how these processes are manifested in tissues outside of the brain, new peripheral biomarkers may also be validated as non-invasive tests to diagnose preclinical and clinical AD. PMID:26402622

  6. Cochlear and cerebrospinal fluid pressure: their inter-relationship and control mechanisms.

    PubMed

    Marchbanks, R J; Reid, A

    1990-06-01

    The patency of the cochlear aqueduct is a key factor in intra-cochlear hydromechanics. If patent, the cerebrospinal fluid (CSF) provides the reference pressure for the perilymph and also to a large extent the endolymph, since Reissner's membrane can only withstand a relatively small pressure differential. The aqueduct often becomes sealed as a natural process of ageing. In this instance the reference pressure is from a source, its position unknown, within the boundaries of the cochlea itself. Relatively large and rapid changes in the cerebrospinal fluid pressure may result from everyday events such as coughing (ca. 175 mm saline) and sneezing (ca. 250 mm saline). The resistive nature of the cochlear aqueduct and the mechanical compliance of the cochlear windows are probably important factors in limiting the amount of stress, and therefore possible damage, which may occur to the cochlea and cochlear windows for a given pressure change within the CSF system. A narrow aqueduct and compliant cochlear windows reduce the risk of structural damage. In practice, this should mean that the risk of structural damage will be increased by any process which reduces the compliance of one or both of the cochlear windows, for example, extremes of middle ear pressure perhaps brought about by Eustachian tube dysfunction or rapid barometric pressure changes. Techniques are now available which provide non-invasive indirect measures of perilymphatic pressure and CSF-perilymphatic pressure transfer. The tympanic membrane displacement measurement technique has been used to provide reliable measures of perilymphatic pressure and CSF-perilymphatic pressure transfer on an individual subject basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2194603

  7. Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood-Brain Barrier Disruption

    SciTech Connect

    Ogami, Ryo Nakahara, Toshinori; Hamasaki, Osamu; Araki, Hayato; Kurisu, Kaoru

    2011-10-15

    Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

  8. Supine Digital Subtraction Myelography for the Demonstration of a Dorsal Cerebrospinal Fluid Leak in a Patient with Spontaneous Intracranial Hypotension: A Technical Note

    PubMed Central

    Carstensen, Michael; Chaudhary, Navjot; Leung, Andrew; Ng, Wai

    2012-01-01

    A patient with spontaneous intracranial hypotension due to a spinal cerebrospinal fluid (CSF) leak required localization of the leakage site prior to surgical management. Conventional, computed tomography and prone digital subtraction myelography failed to localize the dural tear, which was postulated to be dorsally located. We present here a digital subtraction myelographic approach to accurately localize a dorsal site of CSF leakage by injecting iodinated contrast via a lumbar drain with the patient in the supine position. PMID:23378882

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

    PubMed

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

    2005-04-01

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

  10. Quantification of 10 elements in human cerebrospinal fluid from chronic pain patients with and without spinal cord stimulation.

    PubMed

    Korvela, Marcus; Lind, Anne-Li; Wetterhall, Magnus; Gordh, Torsten; Andersson, Marit; Pettersson, Jean

    2016-09-01

    Neuropathic pain affects 1-10% of the general population and is caused by a lesion or disease of the somatosensory nervous system. Spinal cord stimulation (SCS), a method where implanted electrodes stimulate the spinal cord, has been successfully used to treat drug-resistant neuropathic pain, but the mechanism of action is largely unknown. Studies show that SCS changes the protein levels in CSF (cerebrospinal fluid) of pain patients. Several neurological conditions have been shown to alter the elemental composition of CSF. Therefore changes in the levels of ions and trace elements in the CSF may correspond to SCS use. This study used ICP-MS (Inductively coupled plasma mass spectrometry) and ICP-AES (Inductively coupled plasma atomic emission spectroscopy) to quantify 10 elements in CSF from chronic neuropathic pain patients using SCS. The element concentrations in CSF from patients with SCS treatment on/off, were measured. No effect on the element concentrations in CSF from treatment with SCS could be detected. Also, the elemental concentrations in pooled CSF from patients without chronic neuropathic pain was determined and compared to the patients using SCS. The concentration of the elements Ca, Sr, Na, K, P, Mg and Ti were, significantly higher in patients compared to the CSF-control. PMID:27473826

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

    PubMed Central

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

    2014-01-01

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

  12. Extracellular signal-regulated kinase 5 in the cerebrospinal fluid-contacting nucleus contributes to morphine physical dependence in rats.

    PubMed

    Wang, Chun-Guang; Ding, Yan-Ling; Zheng, Tian-Fang; Wei, Jing-Qiu; Liu, He; Chen, Yu-Feng; Wang, Jia-You; Zhang, Li-Cai

    2013-05-01

    The cerebrospinal fluid-contacting nucleus (CSF-CN) may influence actual composition of the CSF for non-synaptic signal transmission via releasing or absorbing bioactive substances, which distributes and localizes in the ventral periaqueductal central gray of the brainstem. Previous studies demonstrated that CSF-CN was involved in neuropathic pain and morphine dependence. Thus, to identify whether extracellular signal-regulated kinase 5 (ERK5) distributed in the CSF-CN and its function on the formation and development of morphine physical dependence, morphine withdrawal-like behavioral test and immunofluorescent technique were used in this research. Morphine was subcutaneously injected by an intermittent and escalating procedure to induce physical dependence, which was measured by withdrawal symptoms. In this study, we found that horseradish peroxidase-conjugated toxin subunit B/p-ERK5 double-labeled neurons expressed in the CSF-CN of normal rats. ERK5 signaling pathway was remarkably activated by naloxone-precipitated withdrawal in the CSF-CN. Moreover, selective attenuation of p-ERK5 expression in the CSF-CN by lateral ventricle injection of BIX02188 could significantly relieve morphine withdrawal symptom. These findings confirmed that the activation of p-ERK5 in the CSF-CN might contribute to morphine physical dependence. PMID:23143893

  13. Increased acidic fibroblast growth factor concentrations in the serum and cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Mashayekhi, Farhad; Hadavi, Mahvash; Vaziri, Hamid Reza; Naji, Mohammad

    2010-03-01

    Acidic fibroblast growth factor (aFGF), also called FGF-1, which influences the proliferation and differentiation of various cell types in vitro, was originally isolated from neural tissue. It is released from the ependymal cells of the cerebral third ventricle into the cerebrospinal fluid (CSF). FGF-1 promotes the survival of neurons. Reactive astrocytes express FGF-1 in the brain of patients with Alzheimer's disease (AD). By comparing the CSF proteome of patients with AD and normal controls it might be possible to identify proteins that have a role in AD. Because CSF is in contact with the extracellular space of the brain, modifications in the brain biochemistry could be reflected in the CSF. The aim of this study was to determine concentrations of serum and CSF FGF-1 in patients with AD. This study consisted of 64 CSF samples, from patients with AD (n=32) and those without (normal controls) (n=32). The level of CSF and serum FGF-1 in patients with AD was higher than in patients without AD. We conclude that FGF-1 is a constant component of human serum and CSF and that FGF-1 may be involved in the pathophysiology of AD. PMID:20079650

  14. Utilization of monoclonal antibodies for detection of Plasmodium falciparum antigen in cerebrospinal fluid of cerebral malaria patients.

    PubMed

    Khushiramani, Rekha; Shrivastava, Sandeep; Varma, Subhash; Batra, Harsh Vardhan; Dubey, Mohan Lal

    2008-08-01

    A uniform protein profile of bands at 34, 43, and 52 kDa was obtained with all the cerebrospinal fluid (CSF) samples of malaria (10 in number) and non-malaria patients (31 in number) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). An immunoreactive band was observed at 43 kDa in CSF samples of cerebral malaria patients but not in non-malaria cases when tested with rabbit anti-Plasmodium falciparum antibodies by Western blot analysis. Eleven reactive monoclonal antibodies against P. falciparum were stabilized and expanded. Nine monoclonal antibodies were reactive to CSF samples of cerebral malaria and non-malaria and P. falciparum antigen by dot-ELISA and a common immunoreactive band at 43 kDa by Western blot. One clone Cl-2 was reactive at 43 kDa with CSF of the cerebral malaria patients and also in P. falciparum antigen but at 66 kDa with non-malarial CSF samples in Western blot. The other two clones (Cl-6 and 14) reacted with 3/31 (90% specific) and 8/31 (74%) CSF samples of non-malaria patients, respectively. The monoclonal antibody based ELISA reported in the present study using clone-6 can therefore offer another possibility for developing rapid, easy-to-perform, low-cost tests for diagnosis of cerebral malaria in CSF samples. Western blot using clone-2 might be useful for the detection of cerebral malaria antigen in CSF. PMID:18707548

  15. Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects.

    PubMed

    Carpenter, Linda L; Tyrka, Audrey R; McDougle, Christopher J; Malison, Robert T; Owens, Michael J; Nemeroff, Charles B; Price, Lawrence H

    2004-04-01

    Previous studies have reported elevated concentrations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) in patients with major depression. Elevations of CSF CRF have also been reported in adult laboratory animals exposed to the stress of brief maternal deprivation or maternal neglect in the neonatal or preweaning period. The present study was designed to determine whether major depression and a history of perceived early adversity in childhood are independently associated with elevated CSF CRF concentrations in adults. In this case-control study, 27 medication-free adults with major depression and 25 matched controls underwent standardized lumbar puncture for collection of a single CSF sample at 1200. Subjects provided data about significant adverse early-life experiences and rated their global perceived level of stress during pre-school and preteen years on a six-point Likert scale. The mean difference in CSF CRF between depressed patients and controls did not reach statistical significance. In a regression model, perceived early-life stress was a significant predictor of CSF CRF, but depression was not. Perinatal adversity and perceived adversity in the preteen adversity years (ages 6-13 years) were both independently associated with decreasing CSF CRF concentrations. The relationship observed between perceived early-life stress and adult CSF CRF concentrations in this study closely parallels recent preclinical findings. More work is needed to elucidate the critical nature and timing of early events that may be associated with enduring neuroendocrine changes in humans. PMID:14702025

  16. COMPARISON BETWEEN MAGNETIC RESONANCE IMAGING ESTIMATES OF EXTRACRANIAL CEREBROSPINAL FLUID VOLUME AND PHYSICAL MEASUREMENTS IN HEALTHY DOGS.

    PubMed

    Reinitz, László Z; Bajzik, Gábor; Garamvölgyi, Rita; Petneházy, Örs; Lassó, András; Abonyi-Tóth, Zsolt; Lőrincz, Borbála; Sótonyi, Péter

    2015-01-01

    Dosages for myelography procedures in dogs are based on a hypothetical proportional relationship between bodyweight and cerebrospinal fluid (CSF) volume. Anecdotal radiographic evidence and recent studies have challenged the existence of such a defined relationship in dogs. The objectives of this prospective cross-sectional study were to describe CSF volumes using magnetic resonance imaging (MRI) in a group of clinically healthy dogs, measure the accuracy of MRI CSF volumes, and compare MRI CSF volumes with dog physical measurements. A sampling perfection with application optimized contrast using different flip-angle evolution MRI examination of the central nervous system was carried out on 12 healthy, male mongrel dogs, aged between 3 and 5 years with a bodyweight range of 7.5-35.0 kg. The images were processed with image analysis freeware (3D Slicer) in order to calculate the volume of extracranial CSF. Cylindrical phantoms of known volume were included in scans and used to calculate accuracy of MRI volume estimates. The accuracy of MRI volume estimates was 99.8%. Extracranial compartment CSF volumes ranged from 20.21 to 44.06 ml. Overall volume of the extracranial CSF increased linearly with bodyweight, but the proportional volume (ml/bodyweight kilograms) of the extracranial CSF was inversely proportional to bodyweight. Relative ratios of volumes in the cervical, thoracic, and lumbosacral regions were constant. Findings indicated that the current standard method of using body weight to calculate dosages of myelographic contrast agents in dogs may need to be revised. PMID:26311617

  17. Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem.

    PubMed

    Orts-Del'immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme

    2012-08-15

    Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in

  18. Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem

    PubMed Central

    Orts-Del'Immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme

    2012-01-01

    Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in

  19. Cyclic adenosine 3', 5'-monophosphate in cerebrospinal fluid during thermoregulation and fever.

    PubMed Central

    Dascombe, M J; Milton, A S

    1976-01-01

    1. Samples of cerebrospinal fluid (c.s.f.) have been taken from the cisterna magna of unanaesthetized cats, whilst rectal temperature was recorded, during exposure of the animals to various ambient temperatures and during fever induced by pyrogen. The concentration of adenosine 3', 5'-monophosphate (cyclic AMP) in samples of c.s.f. has been assayed. 2. Cats exposed to low ambient temperatures (-2 to +2 degrees C) for 3 h maintained body temperature by both behavioural and autonomic heat gain activity. Exposure of cats to high ambient temperatures (44 - 45 degrees C) for 3.5 h caused a rise in body temperatures of about 2.5 degrees C, despite behavioural and autonomic heat loss activity. Neither cold nor heat stress had a significant effect on c.s.f. cyclic AMP. 3. Fever induced by intravenous Shigella dysenteriae (2 and 20 mug/kg) was associated with a dose-related increase in the concentration of cyclic AMP in c.s.f. Paracetamol (75 mg/kg) injected I.P. before the onset of fever, suppressed the increase in both temperature and c.s.f. cyclic AMP in response to pyrogen. Paracetamol (50 and 100 mg/kg), injected after the onset of fever, caused a fall in temperature, which was not associated with a decrease in the concentration of cyclic AMP in c.s.f. 4. Fever induced in cats by intravenous Shigella dysenteriae (20 mug/kg) was associated with an increase in the concentration of cyclic AMP in plasma as well as in c.s.f. 5. The sodium salt of cyclic AMP (0.1-10 mg/kg) injected I.V. into unanaesthetized cats caused a dose-related hypothermia, which was associated with autonomic heat loss activity and a dose-related increase in the concentration of cyclic AMP in cisternal c.s.f., which was not mimicked by adenosine. 6. It is concluded that the raised concentrations of cyclic AMP in c.s.f., in response to pyrogen I.V., do not mediate fever in the cat and that the concentration of cyclic AMP in cisternal c.s.f. may be affected by changes in the plasma concentration of the

  20. Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment

    PubMed Central

    Bayer-Carter, Jennifer L.; Green, Pattie S.; Montine, Thomas J.; VanFossen, Brian; Baker, Laura D.; Watson, G. Stennis; Bonner, Laura M.; Callaghan, Maureen; Leverenz, James B.; Walter, Brooke K.; Tsai, Elaine; Plymate, Stephen R.; Postupna, Nadia; Wilkinson, Charles W.; Zhang, Jing; Lampe, Johanna; Kahn, Steven E.; Craft, Suzanne

    2011-01-01

    Objective To compare the effects of a 4-week high–saturated fat/high–glycemic index (HIGH) diet with a low–saturated fat/low–glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI). Design Randomized controlled trial. Setting Veterans Affairs Medical Center clinical research unit. Participants Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years). Intervention Participants received the HIGH diet (fat, 45% [saturated fat, >25%]; carbohydrates, 35%–40% [glycemic index, >70]; and protein, 15%–20%) or the LOW diet (fat, 25%; [saturated fat, <7%]; carbohydrates, 55%–60% [glycemic index, <5]; and protein, 15%–20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet. Main Outcome Measures The CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition. Results For the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet

  1. Massive Cerebrospinal Fluid Replacement Reduces Delayed Cerebral Vasospasm After Embolization of Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Geng, Liming; Ma, Fei; Liu, Yun; Mu, Yanchun; Zou, Zhongmin

    2016-01-01

    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/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. PMID:27394187

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    1995-08-01

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

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

    PubMed

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

    2008-06-01

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

  5. Cerebrospinal fluid monoamine metabolite concentrations as intermediate phenotypes between glutamate-related genes and psychosis.

    PubMed

    Andreou, Dimitrios; Söderman, Erik; Axelsson, Tomas; Sedvall, Göran C; Terenius, Lars; Agartz, Ingrid; Jönsson, Erik G

    2015-09-30

    Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the d-amino acid oxidase activator (DAOA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis. PMID:26142836

  6. Skull Base Cerebrospinal Fluid Leakage Control with a Fibrin-Based Composite Tissue Adhesive

    PubMed Central

    Rock, Jack P.; Sierra, David H.; Castro-Moure, Frederico; Jiang, Feng

    1996-01-01

    Cerebrospinal fluid (CSF) leaks can be responsible for significant patient morbidity and mortality. While the majority of leaks induced after head trauma will seal without intervention, spontaneous or surgically-induced leaks often require operative repair. Many modifications on standard surgical technique are available for repair of CSF fistulae, but none assures adequate closure. We have studied the efficacy of a novel fibrin-based composite tissue adhesive (CTA) for closure of experimentally-induced CSF leaks in rats. Fistulae were created in two groups of animals. Two weeks after creation of the leaks, the animals were sacrificed and analyzed for persistence of leak. A 58% leakage rate was noted in the control group (n = 12), and no leaks were noted in the experimental group closed after application of CTA to the surgical defect followed by skin closure (n = 11). Comparing the control group to the experimental group, results were statistically significant (p = 0.015). These data suggest that CTA may be effective as an adjunct for the closure of CSF fistulae. ImagesFigure 2Figure 3 PMID:17170969

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-09-20

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

  9. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid.

    PubMed

    Miller, B E; Lipman, J J; Byrne, W L

    1987-12-01

    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. We 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 (less than 1.0 microM) but not at higher (greater than 6.0 microM) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or alpha-chymotrypsin. PMID:3683089

  10. Sensitivity of a radioimmunoassay method for detection of certain viral antibodies in sera and cerebrospinal fluids.

    PubMed Central

    Forghani, B; Schmidt, N J; Lennette, E H

    1976-01-01

    An indirect solid-phase radioimmunoassay (RIA) was applied to titration of serum and cerebrospinal fluid (CSF) antibodies against a variety of viruses including rubella, mumps, measles, herpes simplex, varicella-zoster, and vaccinia. The test used fixed, virus-infected cells as a source of antigen, and conditions for optimal production of viral antigen were determined for each virus-host cell system. In acute, uncomplicated viral infections, sera taken 2 to 5 days after onset generally had low homotypic RIA titers ranging from less than 1:100 to 1:500, whereas convalescent-phase titers ranged from 1:128,000 to 1:512,000. Rubella and measles antibody titers as high as 1:256,000 were demonstrated by RIA in CSF from patients with chronic panencephalitis, whereas homologous antibody titers of 1:4,000 were detected in CSF from acute mumps, herpes simplex, and varicella-zoster virus infections with central nervous system involvement. Some heterotypic antibody was demonstrable by RIA in CSF, but, with the exception of herpes simplex antibody in a mumps virus infection, titers were markedly lower than those to the infecting virus type. RIA generally demonstrated titers at least 1,000 times higher than those obtained by conventional assays such as complement fixation, hemagglutination inhibition, neutralization, and immunofluorescent staining. PMID:187618

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

    PubMed

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

    1999-01-01

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

  12. 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. PMID:26277641

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

    PubMed

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

    2012-03-01

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

  14. Meta-analysis of apolipoprotein E levels in the cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Talwar, Puneet; Sinha, Juhi; Grover, Sandeep; Agarwal, Rachna; Kushwaha, Suman; Srivastava, M V Padma; Kukreti, Ritushree

    2016-01-15

    The possible association between Apolipoprotein E (ApoE) levels in the cerebrospinal fluid (CSF) and Alzheimer's disease (AD) has been studied extensively. However, previous findings have been inconsistent. We conducted a meta-analysis of observational studies, seeking to provide insights into ApoE's potential as a biomarker for AD. A systematic literature search of PubMed (MEDLINE), EMBASE, and Web of Science was performed to retrieve relevant studies evaluating ApoE levels in CSF from AD subjects and controls. The association between ApoE levels in the CSF and AD was estimated by the weighted mean difference (WMD) and 95% confidence interval (CI) using a random-effect model. We identified 24 studies that included 1064AD cases and 1338 non-demented controls. Although the pooled WMD did not indicate a significant association between AD and ApoE levels (-0.30mg/l; 95% CI: -0.69 to 0.09; P=0.13), sub-group analysis controlling for patient sample size (n≥43) revealed significantly lower ApoE levels (WMD: -0.66mg/l; 95% CI: -1.02 to -0.31; P=0.0002) among patients with AD than in controls. Publication bias was absent and sensitivity analysis did not result in any significant change in the pooled estimates, indicating highly stable results. The present meta-analysis indicates the potential of CSF ApoE levels as a predictor of AD association. PMID:26723997

  15. 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.

  16. [Cerebrospinal fluid and plasma aminograms in patients with primary and secondary tumors of the CNS].

    PubMed

    Piek, J; Adelt, T; Huse, K; Bock, W J

    1987-04-01

    16 different free amino acids were determined in cerebrospinal fluid and plasma of each 5 patients with glioblastomas, meningiomas, and low grade gliomas as well as in 21 patients with lumbar disk herniations (control group). The values from the control group were in good accordance with those previously observed in normal adults of 5 studies of the literature. Significant changes were seen only in 6 of 16 amino acids. Absolute values of free CSF amino acids showed significant lower levels of valine, leucine and asparagine in the 3 subgroups whereas serine remained constantly high. The greatest changes were observed in glioblastoma and meningioma patients. Relative values gave similar results. No significant changes were found in CSF-plasma free amino acid relations. The authors conclude that changes of free CSF amino acids are due to a non-specific reaction of the brain itself to tumor growth. The different histology of the tumor does not give specific results. Determination of free CSF amino acids may help in early diagnosis of brain tumor recurrence after operation and to watch the effect of chemotherapy and radiation on brain tumor growth. PMID:3610311

  17. 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. PMID:25565222

  18. 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

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

    PubMed

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

    2015-02-01

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

  20. 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

  1. Effect of Head Position on Cerebrospinal Fluid Pressure in Cats: Comparison with Artificial Model

    PubMed Central

    Klarica, Marijan; Radoš, Milan; Draganić, Pero; Erceg, Gorislav; Orešković, Darko; Maraković, Jurica; Bulat, Marin

    2006-01-01

    Aim To demonstrate that changes in the cerebrospinal fluid (CSF) pressure in the cranial cavity and spinal canal after head elevation from the horizontal level occur primarily due to the biophysical characteristics of the CSF system, ie, distensibility of the spinal dura. Methods Experiments in vivo were performed on cats and a new artificial model of the CSF system with dimensions similar to the CSF system in cats, consisting of non-distensible cranial and distensible spinal part. Measurements of the CSF pressure in the cranial and spinal spaces were performed in chloralose-anesthetized cats (n = 10) in the horizontal position on the base of a stereotaxic apparatus (reference zero point) and in the position in which the head was elevated to 5 cm and 10 cm above that horizontal position. Changes in the CSF pressure in the cranial and spinal part of the model were measured in the cranial part positioned in the same way as the head in cats (n = 5). Results When the cat was in the horizontal position, the values of the CSF pressure in the cranial (11.9 ± 1.1 cm H2O) and spinal (11.8 ± 0.6 cm H2O) space were not significantly different. When the head was elevated 5 cm or 10 cm above the reference zero point, the CSF pressure in the cranium significantly decreased to 7.7 ± 0.6 cm H2O and 4.7 ± 0.7 cm H2O, respectively, while the CSF pressure in the spinal space significantly increased to 13.8 ± 0.7 cm H2O and 18.5 ± 1.6 cm H2O, respectively (P<0.001 for both). When the artificial CSF model was positioned in the horizontal level and its cranial part elevated by 5 cm and 10 cm, the changes in the pressure were the same as those in the cats when in the same hydrostatic position. Conclusions The new model of the CSF system used in our study faithfully mimicked the changes in the CSF pressure in cats during head elevation in relation to the body. Changes in the pressure in the model were not accompanied by the changes in fluid volume in

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

    PubMed

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

    2015-09-01

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

  3. Study of tryptophan metabolism via serotonin in cerebrospinal fluid of patients with noncommunicating hydrocephalus using a new endoscopic technique.

    PubMed

    Comai, Stefano; Longatti, Pierluigi; Perin, Alessandro; Bertazzo, Antonella; Ragazzi, Eugenio; Costa, Carlo V L; Allegri, Graziella

    2006-08-15

    By a recent minimally invasive neuroendoscopic technique, the cerebral ventricles have been reached in a quick, reliable, and harmless way, making possible the study of cerebrospinal fluid (CSF) of the lateral ventricles and, above all, the CSF adjacent to the walls of the third ventricle. Tryptophan, 5-hydroxytryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in CSF by HPLC equipment. Twenty-six patients affected with noncommunicating hydrocephalus were enrolled in the study and, as controls, 28 subjects not suffering from any neurological disease. The concentrations of tryptophan were higher in right ventricular CSF than in lumbar CSF (P < 0.01). 5-HT was detectable in the CSF of the right ventricle of hydrocephalic patients. 5-HIAA was higher in right ventricular CSF than in cisternal and lumbar CSF (P < 0.01), both in controls and in hydrocephalic patients. However, there was a higher concentration of 5-HIAA in right ventricular (P < 0.05) and cisternal (P < 0.01) CSF in hydrocephalic patients in comparison with controls. In the CSF samples withdrawn during neuroendoscopy, 5-HT presented the highest concentrations in the pineal recess. The highest amounts of 5-HIAA were found in the choroid plexus, third and right ventricles, pituitary recess, and aqueduct, and the lowest in pineal recess, subarachnoid space, infundibulum, and interpeduncolar cistern. These results provide new insight into the fate of tryptophan and its metabolites via serotonin in the CSF and suggest the feasibility of the new neuroendoscopic technique for brain metabolic studies. PMID:16721766

  4. Expression of CXCL2 in the serum and cerebrospinal fluid of patients with HIV and syphilis or neurosyphilis.

    PubMed

    Tsai, Hung-Chin; Ye, Shin-Yu; Lee, Susan Shin-Jung; Wann, Shue-Ren; Chen, Yao-Shen

    2014-06-01

    The potential mechanisms for blood-brain barrier damage and the diagnosis of neurosyphilis in HIV patients co-infected with syphilis (HIV-S) are unclear. The aim of the study was to determine the expression of CXCL2 in the serum and cerebrospinal fluid (CSF) of HIV-S patients. A total of 34 HIV patients and 7 controls were enrolled in a HIV clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of CXCL2 were determined by ELISA. Neurosyphilis was defined as a CSF white blood cell count of ≧20 cells/μl or a reactive CSF Venereal Disease Research Laboratory (VDRL). Demographics and medical histories were collected. All the patients with HIV-S were males. Most (80%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≧1:32. The medium age was 37 (range 21-68) years. The medium CD4 T cell counts at the time of the diagnosis of syphilis were 299 (range 92-434) cells/μl. Eight patients (24%) had neurosyphilis based on a reactive CSF VDRL test (n = 5) or increased CSF white blood cell counts of ≧20 cells/μl (n = 3). The concentrations of CSF CXCL2 were significantly higher in patients with HIV and neurosyphilis as compared to HIV with syphilis, HIV, and controls (p = 0.012). There were no significant differences in serum concentrations between the four groups. There was a correlation between CSF CXCL2 concentrations with neurosyphilis (p = 0.017), CSF white blood cell count (p = 0.001), and CSF protein levels (p = 0.005). The CSF level of CXCL2 can be used to distinguish those with or without neurosyphilis in HIV infected patients. PMID:24419746

  5. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

    PubMed

    Luykx, J J; Bakker, S C; Visser, W F; Verhoeven-Duif, N; Buizer-Voskamp, J E; den Heijer, J M; Boks, M P M; Sul, J H; Eskin, E; Ori, A P; Cantor, R M; Vorstman, J; Strengman, E; DeYoung, J; Kappen, T H; Pariama, E; van Dongen, E P A; Borgdorff, P; Bruins, P; de Koning, T J; Kahn, R S; Ophoff, R A

    2015-12-01

    The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (β=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (β=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (β=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects. PMID:25666758

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

    PubMed Central

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

    2016-01-01

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

  7. Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

    PubMed Central

    Cusato, Maria; Accetta, Giovanni; Marinò, Valeria; Procaccio, Francesco; Del Gaudio, Alfredo; Iotti, Giorgio A.; Regazzi, Mario

    2012-01-01

    Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2λ) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent. PMID:22687507

  8. Overton's Rule Helps To Estimate the Penetration of Anti-Infectives into Patients' Cerebrospinal Fluid

    PubMed Central

    Djukic, Marija; Munz, Martin; Sörgel, Fritz; Holzgrabe, Ulrike; Eiffert, Helmut

    2012-01-01

    In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinal fluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUCCSF) to that in serum (AUCCSF/AUCS) correlated positively with the lipid-water partition coefficient at pH 7.0 (log D) (Spearman's rank correlation coefficient rS = 0.40; P = 0.01) and negatively with the molecular mass (MM) (rS = −0.33; P = 0.04). The ratio of AUCCSF to the AUC of the fraction in serum that was not bound (AUCCSF/AUCS,free) strongly correlated with log D (rS = 0.67; P < 0.0001). In the presence of meningeal inflammation, AUCCSF/AUCS also correlated positively with log D (rS = 0.46; P = 0.002) and negatively with the MM (rS = −0.37; P = 0.01). The correlation of AUCCSF/AUCS,free with log D (rS = 0.66; P < 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied. PMID:22106225

  9. Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals.

    PubMed

    Paterson, R W; Bartlett, J W; Blennow, K; Fox, N C; Shaw, L M; Trojanowski, J Q; Zetterberg, H; Schott, J M

    2014-01-01

    We aimed to identify cerebrospinal fluid (CSF) biomarkers associated with neurodegeneration in individuals with and without CSF evidence of Alzheimer pathology. We investigated 287 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects (age=74.9±6.9; 22/48/30% with Alzheimer's disease/mild cognitive impairment/controls) with CSF multiplex analyte data and serial volumetric MRI. We calculated brain and hippocampal atrophy rates, ventricular expansion and Mini Mental State Examination decline. We used false discovery rate corrected regression analyses to assess associations between CSF variables and atrophy rates in individuals with and without amyloid pathology, adjusting in stages for tau, baseline volume, p-tau, age, sex, ApoE4 status and diagnosis. Analytes showing statistically significant independent relationships were entered into reverse stepwise analyses. Adjusting for tau, baseline volume, p-tau, age, sex and ApoE4, 4/83 analytes were significantly independently associated with brain atrophy rate, 1/83 with ventricular expansion and 2/83 with hippocampal atrophy. The strongest CSF predictor for the three atrophy measures was low trefoil factor 3 (TFF3). High cystatin C (CysC) was associated with higher whole brain atrophy and hippocampal atrophy rates. Lower levels of vascular endothelial growth factor and chromogranin A (CrA) were associated with higher whole brain atrophy. In exploratory reverse stepwise analyses, lower TFF3 was associated with higher rates of whole brain, hippocampal atrophy and ventricular expansion. Lower levels of CrA were associated with higher whole brain atrophy rate. The relationship between low TFF3 and increased hippocampal atrophy rate remained after adjustment for diagnosis. We identified a series of CSF markers that are independently associated with rate of neurodegeneration in amyloid-positive individuals. TFF3, a substrate for NOTCH processing may be an important biomarker of neurodegeneration across the Alzheimer

  10. [Significance of measurement of serum and cerebrospinal fluid trace elements in the diagnosis of brain tumors].

    PubMed

    Jiang, H M

    1991-05-01

    Cu, Zn, Cd, Mn, Se in serum and Cu, Cd and Mn in cerebrospinal fluid (CSF) of 150 patients were measured by flame, flameless and hydride generation atomic absorption spectrophotometry. The patients were divided into three groups: malignant brain tumor group (MTG), benign brain tumor group (BTG), and non-neoplastic neurological disease group (no evidence of brain tumor group, NENG). The results were as follows: 1. Serum Cu, Zn, Cd, Mn, Se levels before operation were higher than those after operation; 2. Cu Cd, Mn serum levels were positively correlated with the CSF in the three groups. The correlation coefficients of serum Cu-CSFCU were 0.8935 (MTG), 0.6074 (BTG), 0.5349 NETG); serum Cd-CSFCd 0.7963, 0.2671, 0.5398; serum Mn- CSF Mn 0.5855, 0.4474, 0.5163, (P less than 0.01). 3. Serum and CSF Cu levels in MTG were significantly higher than in BTG and NETG (P less than 0.01). 4. A group of discrimination function equations was established with stepwise discrimination analysis. The six factors, i. e. serum Cu, Cd, Mn, Se and CSF Cu, Mn were significant in the equations. The conformation rate of diagnosis and discrimination by the equations in the malignant and benign brain tumors with clinical diagnosis was 81 percent. The equations could describe the relationship of coordination and antagonism among trace elements in serum and CSF. The authors believe that discrimination equations may have potential use both in diagnosing and discriminating patients in the 3 groups mentioned above and in following patients after excision of the brain tumor. PMID:1786758

  11. Active removal of inorganic phosphate from cerebrospinal fluid by the choroid plexus.

    PubMed

    Guerreiro, Pedro M; Bataille, Amy M; Parker, Sonda L; Renfro, J Larry

    2014-06-01

    The P(i) concentration of mammalian cerebrospinal fluid (CSF) is about one-half that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus acanthias. The objective of the present study was to characterize the possible role of the choroid plexus (CP) in determining CSF P(i) concentration. The large sheet-like fourth CP of the shark was mounted in Ussing chambers where unidirectional (33)P(i) fluxes revealed potent active transport from CSF to the blood side under short-circuited conditions. The flux ratio was 8:1 with an average transepithelial resistance of 87 ± 17.9 Ω·cm(2) and electrical potential difference of +0.9 ± 0.17 mV (CSF side positive). Active P(i) absorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na(+)-free medium, and increasing the K(+) concentration from 5 to 100 mM. Li(+) stimulated transport twofold compared with Na(+)-free medium. Phosphonoformic acid (1 mM) had no effect on active P(i) transport. RT-PCR revealed both P(i) transporter (PiT)1 and PiT2 (SLC20 family) gene expression, but no Na(+)-P(i) cotransporter II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by immunoblot analysis and localized by immunohistochemistry in (or near) the CP apical microvillar membranes of both the shark and rat. PiT1 appeared to be localized primarily to vascular endothelial cells. Taken together, these data indicate that the CP actively removes P(i) from CSF. This process has transport properties consistent with a PiT2, Na(+)-dependent transporter that is located in the apical region of the CP epithelium. PMID:24740787

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

    PubMed

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

    2016-01-01

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

  13. Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer’s disease

    PubMed Central

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

    2010-01-01

    The frequent co-occurrence of Alzheimer disease (AD) pathology in patients with normal pressure hydrocephalus suggests a possible link between ventricular dilation and AD. If enlarging ventricles serve as a marker of faulty cerebrospinal fluid (CSF) clearance mechanisms, then a relationship may be demonstrable between increasing ventricular volume and decreasing levels of amyloid beta peptide (Aβ) in CSF in preclinical and early AD. CSF biomarker data (Aβ, tau, and phosphorylated tau) as well as direct measurements of whole brain and ventricular volumes were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset. The ratio of ventricular volume to whole brain volume was derived as a secondary independent measure. Baseline data were used for the group analyses of 288 subjects classified as being either normal (n=87), having the syndrome of mild cognitive impairment (n=136), or mild AD (n=65). Linear regression models were derived for each biomarker as the dependent variable, using the MRI volume measures and age as independent variables. For controls, ventricular volume was negatively associated with CSF Aβ in APOE ε4 positive subjects. A different pattern was seen in AD subjects, in whom ventricular volume was negatively associated with tau, but not Aβ in ε4 positive subjects. Increased ventricular volume may be associated with decreased levels of CSF Aβ in preclinical AD. The basis for the apparent effect of APOE ε4 genotype on the relationship of ventricular volume to Aβ and tau levels is unknown, but could involve altered CSF-blood-brain barrier function during the course of disease. PMID:20182051

  14. Purely endoscopic pterional extradural approach: A novel technique for repair of cerebrospinal fluid rhinorrhea

    PubMed Central

    Sinha, Ajit Kumar; Goyal, Sumit

    2016-01-01

    Study Design: Retrospective descriptive study of an innovative surgical technique. Objective: To assess the feasibility and success of repair of transfrontal sinus cerebrospinal fluid (CSF) rhinorrhea through pterional transcranial extradural approach using endoscope. Summary of Background Data: Repair of CSF rhinorrhea has seen advancement with the evolution of endoscopic transnasal techniques. However, leaks from defect in the posterior wall of frontal sinus still remain a challenge for the skull base surgeons and requires conventional craniotomy more often. We describe a novel technique to repair these leaks by purely endoscopic pterional extradural (PEPE) approach thereby avoiding complications associated with conventional craniotomy and endoscopic transnasal approaches. Materials and Methods: Thirty-five patients with traumatic CSF rhinorrhea from the posterior wall of frontal sinus underwent repair with the present technique. They were followed up for 6–18 months and were evaluated for feasibility of procedure, recurrence of leak, and occurrence of the fresh neurological deficit. Results: Thirty-five patients underwent CSF rhinorrhea repair using the above technique. The procedure was accomplished in all patients without any intraoperative complications. There was no requirement of blood transfusion in any case. All patients had a cessation of CSF leak in the postoperative period, and there was no recurrence. There was no evidence of frontal lobe retraction injury in any of these patients, and no fresh neurological deficit was observed. Conclusion: This PEPE approach to repair CSF leak through the posterior wall of the frontal sinus is a novel technique in which we can avoid disadvantages associated with both conventional craniotomy as well as transnasal endoscopic approaches. PMID:27114672

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

    PubMed Central

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

    2014-01-01

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

  16. Detection of the GD2+/CD56+/CD45- immunophenotype by flow cytometry in cerebrospinal fluids from a patient with retinoblastoma.

    PubMed

    Shen, Hongqiang; Tang, Yongmin; Xu, Xiaojun; Tang, Hongfeng

    2013-02-01

    Triple-color flow cytometry with a panel of antibodies comprising GD2, CD56, and CD45 was performed to analyze cerebrospinal fluids (CSF) from a patient with retinoblastoma who was suspicious of meningeal metastasis based on clinical presentation. Our results showed that the cells in CSF demonstrated the immunophenotype positive for GD2 and CD56 but negative for CD45 antigen, which suggested the presence of CSF metastasis of retinoblastoma. At the end of eight cycles of intrathecal chemotherapy, CSF specimen was analyzed with Flow cytometry immunophenotyping (FCI) again and the result showed no detectable malignant cells with the same immunophenotype. Our conclusion is that FCI can be a quick and reliable method for the diagnosis of CSF metastasis of retinoblastoma and the immunophenotype (GD2+, CD56+, and CD45-) can be used to recognize residual retinoblastoma cells in CSF. PMID:23126274

  17. Herpes simplex encephalitis without cerebrospinal fluid pleocytosis in a patient with bullous pemphigoid: a case report.

    PubMed

    Nakamura, Yoshitsugu; Kakiuti, Kensuke; Tani, Hiroki; Nakajima, Hideto; Kimura, Fumiharu; Hanafusa, Toshiaki

    2016-06-22

    A 78-year-old woman was diagnosed with bullous pemphigoid 2 months ago, and she had been treated with steroid and plasmapheresis. She developed sudden fever, vomiting, disorientation, and abnormal behavior. Diffusion weighted images and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images showed high-intensity signals in the right temporal lobe hippocampus and right insular cortex. Cerebrospinal fluid (CSF) examination showed normal cell count (4/mm(3)), but was positive for HSV1-DNA by PCR. She was diagnosed with herpes simplex encephalitis (HSE), and acyclovir was started on the first day of admission. She had complete recovery, and was discharged. She didn't show CSF pleocytosis throughout her course of HSE. No CSF pleocytosis could be due probably to her immunosuppressed state under the steroid therapy for bullous pemphigoid. Because the morbidity and mortality of HSE is drastically reduced by early antiviral treatment, it is important to accelerate the diagnosis and treatment of HSE, especially in immunosuppressed or immunocompromised hosts. PMID:27247185

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

    PubMed

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

    2014-06-30

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

  19. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

    PubMed Central

    Wang, Yuxuan; Springer, Simeon; Zhang, Ming; McMahon, K. Wyatt; Kinde, Isaac; Dobbyn, Lisa; Ptak, Janine; Brem, Henry; Chaichana, Kaisorn; Gallia, Gary L.; Gokaslan, Ziya L.; Groves, Mari L.; Jallo, George I.; Lim, Michael; Olivi, Alessandro; Quinones-Hinojosa, Alfredo; Rigamonti, Daniele; Riggins, Greg J.; Sciubba, Daniel M.; Weingart, Jon D.; Wolinsky, Jean-Paul; Ye, Xiaobu; Oba-Shinjo, Sueli Mieko; Marie, Suely K. N.; Holdhoff, Matthias; Agrawal, Nishant; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Bettegowda, Chetan

    2015-01-01

    Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57–88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88–100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher’s exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord. PMID:26195750

  20. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    PubMed

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  1. Sustained increases in plasma C-type natriuretic peptides fail to increase concentrations in cerebrospinal fluid: Evidence from pregnant sheep.

    PubMed

    Wilson, Michele O; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

    2015-07-01

    C-type natriuretic peptide (CNP) is a paracrine growth factor with high abundance in CNS tissues and cerebrospinal fluid (CSF). Consistent with findings of CNP transcripts in the cerebral microvasculature and hypothalamus, CNP increases the permeability of the blood-brain barrier and reduces food intake when administered intracerebroventricularly in rodents. Whether high concentrations of CNP in plasma can affect CSF levels is unknown. Accordingly we have studied changes (days 4, 87 and 116) in concurrent plasma and CSF concentrations of CNP peptides in pregnant sheep - a physiologically unique setting in which plasma CNP is elevated for prolonged periods. Preliminary studies in non pregnant sheep showed stable CNP levels in CSF during repetitive sampling. Compared with values in non pregnant controls, plasma concentrations of CNP peptides were markedly raised (30-fold) at days 87 and 116 in pregnant sheep, yet CSF levels in the two groups did not differ. CNP peptides in CSF decreased from day 4 to day 87 in pregnant sheep, possibly reflecting an adaptive response of the cerebral vasculature to increased hemodynamic load. We conclude that sustained high concentrations of CNP - far exceeding levels encountered in human pathophysiology - fail to affect CNP peptide levels in CSF. PMID:25913855

  2. Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo

    PubMed Central

    Nedosekin, Dmitry A.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Moore, Christopher L.; Rusch, Nancy J.; Smeltzer, Mark S.; Zharov, Vladimir P.; Galanzha, Ekaterina I.

    2014-01-01

    Circulating cells, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early-stage of diseases. Here, we introduce novel CSF tests based on in vivo multicolor photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor-bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20-times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label-free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits. PMID:23681943

  3. Cognitive performance and cerebrospinal fluid biomarkers of neurodegeneration: a study of patients with bipolar disorder and healthy controls.

    PubMed

    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. Lumbar puncture-related cerebrospinal fluid leakage on magnetic resonance myelography: is it a clinically significant finding?

    PubMed Central

    2013-01-01

    Background Post-dural puncture headache (PDPH) due to excessive cerebrospinal fluid (CSF) leakage is a well-known complication of lumbar puncture. Although various factors, especially the type of spinal needle, have been demonstrated to be associated with PDPH, the clinical implications of CSF leakage detected on magnetic resonance myelography (MRM) images remain unclear. The objective of this case–control study was to evaluate the association between radiologically visualized CSF leakage and PDPH. Methods Clinical data including patients’ age and gender, types of spinal needle, duration of bed rest, interval between lumbar puncture procedures and MRM studies, and incidence of PDPH were compared between patients who were radiologically-positive and -negative for CSF leakage. Results Of the 22 patients with definite CSF leakage on MRM images, most were asymptomatic (86%, 19/22). The remaining three patients, who were suffering from PDPH, only complained of headaches and were treated conservatively. In a review of patients’ clinical data, there were no significant differences in any parameter including the incidence of PDPH between the 22 patients who were radiologically-positive for CSF leakage and the 31 radiologically-negative patients. Conclusion The significance of radiologically visualized CSF leakage should not be overestimated, as most such incidents are not associated with PDPH and do not require any treatment. PMID:24160550

  5. MicroRNA-29a Is a Candidate Biomarker for Alzheimer's Disease in Cell-Free Cerebrospinal Fluid.

    PubMed

    Müller, Mareike; Jäkel, Lieke; Bruinsma, Ilona B; Claassen, Jurgen A; Kuiperij, H Bea; Verbeek, Marcel M

    2016-07-01

    The identification of reliable biomarkers for Alzheimer's disease (AD) remains challenging. Recently, abnormal levels of microRNAs (miRNAs) miR-27a, miR-29a, miR-29b, and miR-125b in cerebrospinal fluid (CSF) of AD patients were reported. We aimed to confirm the biomarker potential of these miRNAs for AD diagnosis. Additionally, we examined the influence of blood contamination on CSF miRNA levels as potential confounding factor. We studied expression levels of the four miRNAs by quantitative PCR in CSF samples of AD patients and non-demented controls, and in blood-spiked CSF. Levels of miR-29a, but not of the other three miRNAs, were increased by a factor of 2.2 in CSF of AD patients. Spiking of small amounts of blood into CSF revealed that miR-27a and miR-29a, but not miR-125b levels were strongly influenced by the number of blood cells in the sample. In conclusion, miR-29a may be a candidate biomarker for AD, but only when used in cell-free CSF. PMID:25895659

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

    PubMed Central

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

    2015-01-01

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

  7. 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

  8. MGMT promoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma

    PubMed Central

    WANG, ZHENG; JIANG, WEI; WANG, YAHONG; GUO, YANG; CONG, ZHENG; DU, FANGFANG; SONG, BIN

    2015-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a conventional technique to predict the prognosis or individualized treatment of glioma in tumor tissue following surgery or biopsy. However, the technique cannot be applied in those glioma patients with concomitant neurological dysfunctions or advanced age. The present study aimed to find a new minimally invasive and efficient alternative method for the detection of MGMT promoter methylation. The expression of MGMT promoter methylation was assessed in peripheral blood and cerebrospinal fluid (CSF), and compared to the corresponding tumor tissue from glioma patients. The 89 patients in the study [32 World Health Organization (WHO) grade II, 19 WHO grade III and 38 WHO grade IV) were pathologically-diagnosed glioma and received radiation therapy following sample collection. The resected glioma tumor tissue (89), corresponding serum (89) and CSF (78) samples were collected for the detection of MGMT promoter methylation using methylation-specific polymerase chain reaction. The sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum were compared. Among the tumor tissue samples, 51/89 (57.3%) showed MGMT promoter methylation. The specificity of the detection in the CSF and serum samples reached 100%. The sensitivity of MGMT promoter methylation detection in CSF and serum were 26/40 (65.0%) and 19/51 (37.3%), respectively (P<0.05). In the WHO II, III and IV subgroups, the sensitivities of MGMT promoter methylation detection using CSF were 8/12 (66.7%), 11/18 (61.1%) and 7/10 (70.0%), respectively, which were significantly higher than the sensitivities using serum (7/21, 33.3%; 7/19, 36.8%; and 5/11, 45.5%, respectively P<0.05). Among patients with residual postoperative tumors, the sensitivities of detecting MGMT promoter methylation using CSF and serum were 18/25 (72.0%) and 10/24 (41.7%), respectively, both of which were significantly higher than the corresponding values

  9. Postmortem catecholamine levels in pericardial and cerebrospinal fluids with regard to the cause of death in medicolegal autopsy.

    PubMed

    Ishikawa, Takaki; Quan, Li; Michiue, Tomomi; Kawamoto, Osamu; Wang, Qi; Chen, Jian-Hua; Zhu, Bao-Li; Maeda, Hitoshi

    2013-05-10

    Previous studies have suggested that postmortem serum catecholamine levels reflect the magnitude of physical stress responses or toxic/hyperthermic neuronal dysfunction during the death process. The present study investigated postmortem adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in pericardial fluid (PCF) and cerebrospinal fluid (CSF) with regard to the cause of death, compared with right heart blood levels, in serial medicolegal autopsy cases with a postmortem time within 48 h (n=494). Correlations between PCF and CSF Adr levels, and those among right heart blood, PCF, and CSF DA levels were marked (r=0.66-0.83, p<0.0001), but were otherwise lower (r=0.22-0.44). With regard to the cause of death, Adr and Nad levels in PCF, CSF, and right heart blood mostly presented similar findings: these levels were generally high in injury, intoxication, and hyperthermia (heatstroke), but were low in hypothermia (cold exposure). DA levels at each site were higher in injury and intoxication. In addition, higher levels were detected for Nad levels in sharp instrument injury, as well as Adr, Nad, and DA in carbon monoxide intoxication at each site, and for CSF Nad in psychotropic drug intoxication. These findings suggest that characteristic elevations in Adr, Nad, and DA levels in PCF and CSF are involved in systemic responses to fatal stress and toxic neuronal dysfunction, reflecting the magnitude of such responses in individual cases. PMID:23597740

  10. Proteomic analysis of cerebrospinal fluid in amyotrophic lateral sclerosis

    PubMed Central

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

    2016-01-01

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

  11. Risk factors for suicide among patients with schizophrenia: a cohort study focused on cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid

    PubMed Central

    Neider, Daniel; Lindström, Leif H; Bodén, Robert

    2016-01-01

    Background The objective of this study was to investigate the association between 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF), bullying, and later suicide among patients with schizophrenia. Methods Ninety-nine patients with schizophrenia were included. Correlations of clinical factors, 5-HIAA and HVA, and later suicide were investigated. Results Twelve patients committed suicide (12%) during a 28-year follow-up period. Later suicide was correlated to bullying in childhood (P=0.02) and a lower quotient of HVA/5-HIAA in CSF (P<0.05). Conclusion Suicide in schizophrenia is related to childhood exposedness and CSF neurotransmitter levels. PMID:27468235

  12. Utility of Measuring (1,3)-β-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection

    PubMed Central

    Lyons, Jennifer L.; Thakur, Kiran T.; Lee, Rick; Watkins, Tonya; Pardo, Carlos A.; Carson, Kathryn A.; Markley, Barbara; Finkelman, Malcolm A.; Marr, Kieren A.; Roos, Karen L.

    2014-01-01

    (1-3)-β-d-Glucan (BDG) from cerebrospinal fluid (CSF) is a promising marker for diagnostic and prognostic aid of central nervous system (CNS) fungal infection, but its relationship to serum values has not been studied. Herein, we detected BDG from CSF at levels 2-fold lower than those in serum in patients without evidence of fungal disease but 25-fold higher than those in in serum in noncryptococcal CNS fungal infections. CSF BDG may be a useful biomarker in the evaluation of fungal CNS disease. PMID:25378578

  13. [Usefulness of endotoxin-specific limulus test for the measurement of endotoxin in cerebrospinal fluid in diagnosis of bacterial meningitis].

    PubMed

    Ichinohe, S; Inada, K; Nemoto, T; Murata, A; Ichinohe, N; Fujiwara, T; Yoshida, M

    1995-11-01

    Using a new endotoxin-specific chromogneic limulus assay (Endoscopy test), endotoxin concentrations were measured in 93 specimens of cerebrospinal fluid (CSF) from 66 pediatric patients. Eighteen patients were diagnosed as having menigitios. Of these, 6 cases (group A) with gram-negative meningitis proven by culture had high CSF endotoxin concentrations of 115.3, (82-133) (median, range) pg/ml. Ten cases (group B) with gram-positive or aseptic meningitis had endotoxin concentrations of 2.15 (0.1-3.6) pg ml. Other 2 cases with bacterial meningitis (group C), in whom no pathogen was detected, had CSF endotoxin concentrations of more than 100 pg/ml. Four cases with encephalitis (group D) and 45 cases with non-meningitis or non- encephalitis (group E), had CSF endotoxin concentrations of less than 5 pg/ml. Despite a negative culture after antibiotic treatment in group A patients, endotoxin was cleared slowly from the CSF. A clearing of endotoxin from CSF was followed by alleviation of fever with a more gradual decline in CRP values. In 2 cases of group C, the negative bacterial culture appeared to be attributable to the previous treatment with antibiotics. However, these patients had high CSF endotoxin levels, indicating gram negative bacterial meningitis. In 17 CSF specimens from 5 patients of group A, in whom Haemophilus influenzae was detected on admission, an additional a latex agglutination test for the detection of H. influenzae polysaccharide antigen was performed. Only 3 specimens from 3 patients with CSF endotoxin concentrations of more than 80 pg/ml had a positive agglutination test. These results suggest that quantitation of endotoxin concentrations is useful for the diagnosis of gram-negative meningitis. And also, the clearance of endotoxin from CSF during treatment appears to be useful in determining the timing of when antibiotic should be stopped. PMID:8708402

  14. α-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system.

    PubMed

    Mollenhauer, Brit; Trautmann, Ellen; Otte, Birgit; Ng, Juliana; Spreer, Annette; Lange, Peter; Sixel-Döring, Friederike; Hakimi, Mansoureh; Vonsattel, Jean-Paul; Nussbaum, Robert; Trenkwalder, Claudia; Schlossmacher, Michael G

    2012-07-01

    The source of Parkinson disease-linked α-synuclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (Q(aSyn)) to the albumin quotient (Q(albumin)) to evaluate its relation to blood-CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, β-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that Q(aSyn) did not rise or fall with Q(albumin) values, a relative measure of blood-CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions, in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and β-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF. PMID:22426833

  15. Detection of High Cerebrospinal Fluid Levels of (1→3)-β-d-Glucan in Cryptococcal Meningitis

    PubMed Central

    Rhein, Joshua; Bahr, Nathan C.; Morawski, Bozena M.; Schutz, Charlotte; Zhang, Yonglong; Finkelman, Malcolm; Meya, David B.; Meintjes, Graeme; Boulware, David R.

    2014-01-01

    Background  (1→3)-β-d-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for patients infected with human immunodeficiency virus (HIV) and presenting with suspected cryptococcal meningitis. Methods  The Fungitell assay was used to measure BDG concentrations in cerebrospinal fluid (CSF) (n = 177) and serum (n = 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG's relationship with mortality. Results  The Fungitell BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). Cerebrospinal fluid BDG concentrations at diagnosis were median (interquartile range) 343 (200–597) pg/mL in cryptococcal patients and 37 (23–46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were ≥10 000 colony-forming units/mL. (1→3)-β-d-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho = 0.820; P < .001), CSF CRAG lateral flow assay titers (rho = 0.780, P < .001), and monocyte chemotactic protein-1 levels in CSF (P = .047). In patients with cryptococcal meningitis, BDG ≥500 pg/mL at diagnosis was associated with increased 10-week mortality. Conclusions  (1→3)-β-d-Glucan is detectable in the CSF of HIV-infected patients with Cryptococcus, and it may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly

  16. Assessment of cerebrospinal fluid flow patterns using the time-spatial labeling inversion pulse technique with 3T MRI: early clinical experiences.

    PubMed

    Abe, Kayoko; Ono, Yuko; Yoneyama, Hiroko; Nishina, Yu; Aihara, Yasuo; Okada, Yoshikazu; Sakai, Shuji

    2014-06-01

    CSF imaging using the time-spatial labeling inversion pulse (time-SLIP) technique at 3T magnetic resonance imaging (MRI) was performed to assess cerebrospinal fluid (CSF) dynamics. The study population comprised 15 healthy volunteers and five patients with MR findings showing expansive dilation of the third and lateral ventricles suggesting aqueductal stenosis (AS). Signal intensity changes were evaluated in the tag-labeled CSF, untagged brain parenchyma, and untagged CSF of healthy volunteers by changing of black-blood time-inversion pulse (BBTI). CSF flow from the aqueduct to the third ventricle, the aqueduct to the fourth ventricle, and the foramen of Monro to the lateral ventricle was clearly rendered in all healthy volunteers with suitable BBTI. The travel distance of CSF flow as demonstrated by the time-SLIP technique was compared with the distance between the aqueduct and the fourth ventricle. The distance between the foramen of Monro and the lateral ventricle was used to calculate the CSF flow/distance ratio (CD ratio). The CD ratio at each level was significantly reduced in patients suspected to have AS compared to healthy volunteers. CSF flow was not identified at the aqueductal level in most of the patients. Two patients underwent time-SLIP assessments before and after endoscopic third ventriculostomies (ETVs). CSF flow at the ETV site was confirmed in each patient. With the time-SLIP technique, CSF imaging is sensitive enough to detect kinetic changes in CSF flow due to AS and ETV. PMID:24976193

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

    PubMed Central

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

    2016-01-01

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

  18. Detection of Nesopora caninum-specific DNA from cerebrospinal fluid by polymerase chain reaction in a dog with confirmed neosporosis.

    PubMed

    Ishigaki, Kyohei; Noya, Masahiko; Kagawa, Yumiko; Ike, Kazunori; Orima, Hiromitsu; Imai, Soichi

    2012-08-01

    A one-month male Greyhound dog presented with a swinging gait of the hindlimbs, and later developed muscular atrophy of the femoral region and hyperextension of hindlimbs. The dog had positive serum IFAT titers to Neospora caninum, but a negative titer in the cerebrospinal fluid (CSF). N. caninum-specific DNA was amplified from the CSF using a semi-nested polymerase chain reaction assay. Clusters of protozoa in biopsied muscle fibers were subsequently confirmed as N. caninum tachyzoites by immunohistochemical examination. Early recognition and treatment are necessary for effective recovery of clinical canine neosporosis, but antemortem diagnosis is difficult. We suggest that the detection of parasite deoxyribonucleic acid in the CSF is a useful antemortem diagnostic method in facilitating treatment of this disease. PMID:22446406

  19. Middle cerebral artery territory infarct due to Cryptococcus infectionstitle: an uncommon indication for cerebrospinal fluid analysis in stroke patients.

    PubMed

    Cachia, David; Singh, Charanjeet; Tetzlaff, Michael T; Penas-Prado, Marta

    2015-08-01

    Cryptococcal meningitis is the most common manifestation of cryptococcosis and is caused by the encapsulated yeast organism Cryptococcus neoformans. It occurs most commonly in patients with impaired cell-mediated immunity such as in HIV infection; patients with hematological malignancies; patients post solid-organ transplantation; on chronic steroids or immunosuppressants. Clinically, stroke can arise as a complication of cryptococcal meningitis. While cerebrospinal fluid (CSF) examination is usually not indicated for evaluation of stroke patients, demonstration of cryptococcal yeast forms in CSF is valuable in guiding appropriate therapy in arterial stroke caused by Cryptococci. Herein, we describe the CSF and radiologic correlation in a female patient who presented with disseminated cryptococcosis, cryptococcal meninigitis and a middle cerebral artery infarct. PMID:25352313

  20. A case of chronic subdural hematoma following lumbar drainage for the management of iatrogenic cerebrospinal fluid rhinorrhea: pitfalls and lessons.

    PubMed

    Tan, Vincent Eng-Soon; Liew, Donald

    2013-01-01

    Chronic subdural hematoma as a complication of lumbar drain placement for the management of iatrogenic cerebrospinal fluid (CSF) leak has not been previously documented in the literature. We describe such a case in a 69-year-old man who presented with right nasal obstruction secondary to an inverted papilloma involving the paranasal sinuses. The patient underwent endoscopic sinus surgery, which included a medial maxillectomy. Surgery was complicated by a small CSF leak, which was repaired intraoperatively. Five days later, the patient experienced CSF rhinorrhea, and a lumbar drain was inserted. He developed overdrainage symptoms but was well when he was discharged. However, 22 days later he returned with right hemiparesis. Computed tomography of the brain showed a left frontoparietal subdural hematoma with a mass effect. The neurosurgical team performed an emergency drainage procedure, and the patient experienced a complete neurologic recovery. We discuss the pitfalls of lumbar drainage, the possible pathophysiology of overdrainage, and the lessons learned from this case. PMID:24170465

  1. Resolution of Chronic Aspiration Pneumonitis Following Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Fistula of the Skull Base

    PubMed Central

    Seltzer, Justin; Babadjouni, Arash; Wrobel, Bozena B.; Zada, Gabriel

    2016-01-01

    Spontaneous cerebrospinal fluid (CSF) rhinorrhea due to a skull base defect requires prompt diagnosis and treatment. Multiple surgical options are available for repairing the fistula, including the two-layer “fascial apposition” method and use of a pedicled nasal-septal flap. A 44-year-old obese woman presented with 4 months of progressive cough, exertional dyspnea, hoarseness, and intermittent fluid drainage from the right nostril. Chest computed tomography (CT) imaging and bronchoscopy showed chronic pneumonitis, which was confirmed by pulmonary wedge resection. CT and magnetic resonance imaging of the skull base, as well as laboratory analysis of the nasal fluid for β2-transferrin, confirmed a skull base defect causing CSF rhinorrhea. During surgery, insertion of a lumbar drain with the intrathecal fluorescein administration was performed, followed by endoscopic endonasal repair using an autologous fascial apposition graft and pedicled nasal-septal flap. Both the CSF leak and the pulmonary complications resolved following the operation with no symptoms at 11-month follow-up. This is the first reported case of spontaneous CSF rhinorrhea complicated by chronic aspiration and pneumonitis. Increased diagnostic complexity due to chronic pulmonary complications resulted in unnecessary interventions and treatment delays. Prompt recognition of spontaneous CSF leaks is essential to prevent potentially harmful complications. PMID:27247911

  2. Resolution of Chronic Aspiration Pneumonitis Following Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Fistula of the Skull Base.

    PubMed

    Seltzer, Justin; Babadjouni, Arash; Wrobel, Bozena B; Zada, Gabriel

    2016-06-01

    Spontaneous cerebrospinal fluid (CSF) rhinorrhea due to a skull base defect requires prompt diagnosis and treatment. Multiple surgical options are available for repairing the fistula, including the two-layer "fascial apposition" method and use of a pedicled nasal-septal flap. A 44-year-old obese woman presented with 4 months of progressive cough, exertional dyspnea, hoarseness, and intermittent fluid drainage from the right nostril. Chest computed tomography (CT) imaging and bronchoscopy showed chronic pneumonitis, which was confirmed by pulmonary wedge resection. CT and magnetic resonance imaging of the skull base, as well as laboratory analysis of the nasal fluid for β2-transferrin, confirmed a skull base defect causing CSF rhinorrhea. During surgery, insertion of a lumbar drain with the intrathecal fluorescein administration was performed, followed by endoscopic endonasal repair using an autologous fascial apposition graft and pedicled nasal-septal flap. Both the CSF leak and the pulmonary complications resolved following the operation with no symptoms at 11-month follow-up. This is the first reported case of spontaneous CSF rhinorrhea complicated by chronic aspiration and pneumonitis. Increased diagnostic complexity due to chronic pulmonary complications resulted in unnecessary interventions and treatment delays. Prompt recognition of spontaneous CSF leaks is essential to prevent potentially harmful complications. PMID:27247911

  3. Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis.

    PubMed

    Moreira, M A; Souza, A L S; Lana-Peixoto, M A; Teixeira, M M; Teixeira, A L

    2006-04-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5 +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease. PMID:16612466

  4. A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Belgium.

    PubMed

    Somers, Charisse; Struyfs, Hanne; Goossens, Joery; Niemantsverdriet, Ellis; Luyckx, Jill; De Roeck, Naomi; De Roeck, Ellen; De Vil, Bart; Cras, Patrick; Martin, Jean-Jacques; De Deyn, Peter-Paul; Bjerke, Maria; Engelborghs, Sebastiaan

    2016-08-10

    During the past ten years, over 5,000 cerebrospinal fluid (CSF) samples were analyzed at the Reference Center for Biological Markers of Dementia (BIODEM), UAntwerp, for core Alzheimer's disease (AD) CSF biomarkers: amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: Aβ1-42 <638.5 pg/mL, T-tau >296.5 pg/mL, P-tau181P >56.5 pg/mL. A CSF biomarker profile was considered to be suggestive for AD if the CSF Aβ1-42 concentration was below the cutoff, in combination with T-tau and/or P-tau181P values above the cutoff (IWG2 criteria for AD). Biomarker analyses were requested for following clinical indications: 1) neurochemical confirmation of AD in case of clinical AD, 2) neurochemical confirmation of AD in case of doubt between AD and a non-AD dementia, 3) neurochemical diagnosis of prodromal AD in case of mild cognitive impairment, 4) neurochemical confirmation of AD in case of psychiatric symptoms (like depression, psychosis), or 5) other clinical indications. During these ten years, the number of yearly referred samples increased by 238% and clinical indications for referral showed a shift from neurochemical confirmation of AD in case of clinical AD to differential dementia diagnosis in case of doubt between AD and a non-AD dementia. Four percent of the patients also had a postmortem neuropathological examination. Together, these biomarker data were the basis for several research papers, and significantly contributed to the validation of these biomarkers in autopsy-confirmed subjects. PMID:27567807

  5. Oligoclonal bands in the cerebrospinal fluid of amyotrophic lateral sclerosis patients with disease-associated mutations

    PubMed Central

    Mencacci, Niccolò E.; Morelli, Claudia; Doretti, Alberto; Rusconi, Daniela; Colombrita, Claudia; Sangalli, Davide; Verde, Federico; Finelli, Palma; Messina, Stefano; Ratti, Antonia; Silani, Vincenzo

    2014-01-01

    In amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) analysis is usually performed to exclude inflammatory processes of the central nervous system. Although in a small subset of patients an intrathecal synthesis of IgG is detectable, usually there is no clear explanation for this evidence. This study investigates the occurrence of oligoclonal bands (OCBs) in the CSF of a large series of ALS patients, attempting a correlation with genotype data. CSF was collected from 259 ALS patients. CSF parameters were measured according to standard procedures, and detection of OCBs performed by isoelectric focusing. The patients were screened for mutations in SOD1, FUS, TARDBP, ANG, OPTN, and C9ORF72. We observed the presence of OCBs in the CSF of 9/259 ALS patients (3.5 %), and of disease-associated mutations in 12 cases. OCBs were significantly more frequent in mutation carriers compared to the remaining cohort (3/12 vs 6/247; p < 0.01). Among patients with OCBs, two patients had the TARDBP p.A382T mutation (one of which in homozygous state), and one the ANG p.P-4S variant. Both patients carrying the p.A382T mutation had an atypical phenotype, one of them manifesting signs suggestive of a cerebellar involvement, and the other presenting neuroradiological findings suggestive of an inflammatory disorder of the central nervous system. Our results suggest that ALS patients with OCBs may harbor mutations in disease-causing genes. We speculate that mutations in both TARDBP and ANG genes may disrupt the blood–brain barrier (BBB), promoting local immune responses and neuroinflammation. The role of mutant TARDBP and ANG genes on BBB integrity of ALS patients warrants further investigation. PMID:22752089

  6. Decreased homovanilic acid in cerebrospinal fluid correlates with impaired neuropsychologic function in HIV-1-infected patients.

    PubMed

    di Rocco, A; Bottiglieri, T; Dorfman, D; Werner, P; Morrison, C; Simpson, D

    2000-01-01

    To determine whether dopamine metabolism is abnormal in HIV infected patients and whether dopamine metabolism abnormalities are related to specific neuropsychologic characteristics in HIV-infected patients, we measured cerebrospinal fluid (CSF) levels of homovanilic acid (HVA), the primary dopamine metabolite, in 10 HIV-infected patients and compared it to HVA levels in CSF in a group of 13 healthy control subjects. HIV-infected patients were also assessed with a battery of neuropsychologic tests and HVA levels were then correlated with performance on specific neuropsychologic tests. The mean (+/-SD) HVA level in CSF was 100.9 +/- 29.3 nmol/L in the HIV-infected study group and 230.5 +/- 50.0 nmol/L in the non-HIV-infected control group (p < 0.0001). The decrease in concentrations of HVA in CSF correlated with impairment on performance on neuropsychologic testing (Spearman r = 0.67; p = 0.03). When the relationship between HVA levels and specific cognitive domains was evaluated, we observed trends for positive correlation between HVA levels and tests that measure motor speed (r = 0.59; p = 0.074) and those testing attention, concentration, and executive control (r = 0.54; p = 0.108). There was no relationship between performance on memory tests and CSF HVA levels (r = -0.0061; p = 0.987). These results further support the hypothesis that dopaminergic dysfunction plays an important role in the pathogenesis of AIDS dementia complex (ADC) and suggest that specific motor and cognitive abnormalities may be related to depressed dopaminergic activity. This may have important implications for the development of treatments or preventive strategies for ADC. PMID:11020122

  7. Concentration of soluble adhesion molecules in cerebrospinal fluid and serum of epilepsy patients.

    PubMed

    Luo, Jing; Wang, Wei; Xi, Zhiqin; Dan, Chen; Wang, Liang; Xiao, Zheng; Wang, Xuefeng

    2014-12-01

    Mounting evidence supports the involvement of brain inflammation and the associated blood-brain barrier damage from which spontaneous and recurrent seizures originate. Detection of the soluble form of adhesion molecules (AM) has also been proven to predict outcomes in central nervous system (CNS) disorders. A recent study has shown that expression of AM in brain vessels was upregulated 24 h after kainic acid (KA) induced seizures. The aim of the present study was to investigate soluble AM levels in the cerebrospinal fluid (CSF) and serum of epilepsy patients. Paired CSF and serum samples were analyzed by sandwich enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Increased serum concentrations of sICAM-1 were present in epileptic patients (41 localization-related of unknown etiology, 19 idiopathic generalized). Serum sICAM-1 level in drug-refractory epilepsy was elevated as compared to new diagnosis epilepsy and drug-responsive epilepsy. CSF sVCAM-1 and serum sVCAM-1 concentrations in the epilepsy group were higher as compared to the neurosis group. Moreover, CSF sVCAM-1 and serum sVCAM-1 concentrations in drug-refractory epilepsy were raised as compared to drug-responsive epilepsy and new diagnosis epilepsy. However, there were no significant differences in concentrations of CSF sICAM-1 between the epilepsy and neurosis groups. Our results suggest that sVCAM-1 and sICAM-1 could play an important role in the drug-refractory epilepsy. PMID:25001004

  8. Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma.

    PubMed

    Strehlow, Felicitas; Bauer, Sandra; Martus, Peter; Weller, Michael; Roth, Patrick; Schlegel, Uwe; Seidel, Sabine; Scheibenbogen, Carmen; Korfel, Agnieszka; Kreher, Stephan

    2016-08-01

    Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL. OPN concentrations in CSF from 37 patients with CNSL (29 with primary CNSL and 8 with secondary CNS involvement of systemic lymphoma) and 36 controls [6 patients with inflammatory CNS disease other than multiple sclerosis (MS), 8 with MS, 9 with glioblastoma (GBM) and 13 healthy controls] were determined using an enzyme-linked immunosorbent assay. Non-parametric tests and receiver operating characteristic (ROC) curves were performed for determination of diagnostic accuracy. Median CSF OPN level in all CNSL patients was 620 ng/mL and higher than in patients with inflammatory CNS disease (356 ng/mL); P < .05, MS (163 ng/mL); P < .01, GBM (41 ng/mL); P < .01, or healthy controls (319 ng/mL); P < .01. The area under the ROC curve was 0.865 [95 % confidence interval (CI) 0.745-0.985] for differentiating CNSL and patients with inflammatory CNS disease; 0.956 (95 % CI 0.898-1.000) for CNSL and MS patients; 0.988 (95 % CI 0.964-1.000) for CNSL and GBM patients, and 0.915 (95 % CI 0.834-0.996) for CNSL patients and healthy controls. In multivariate analysis, high CSF OPN level was associated with shorter progression-free (HR 1.61, 95 % CI 1.13-2.31; P = .009) and overall survival (HR 1.52, 95 % CI 1.04-2.21; P = .029). CSF OPN is a potential biomarker in CNSL. PMID:27294357

  9. BAFF is decreased in the cerebrospinal fluid of multiple sclerosis at clinical onset.

    PubMed

    Puthenparampil, M; Miante, S; Federle, L; Zanetta, C; Toffanin, E; Ruggero, S; Rinaldi, F; Gallo, P

    2016-08-15

    B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset. Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, QBAFF) and Index (QBAFF/QAlb, BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (p<0.05). BAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (p<0.01). A significant inverse correlation between QIgG and QBAFF (r: -0.4, p<0.05) and between BAFF index and IgGIF (r: -0.4, p<0.05) or IgG Index (r: -0.4, p=0.05) was found in IgGOB+. The decreased CSF levels of BAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. PMID:27397077

  10. Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.

    PubMed

    Matejčíková, Z; Mareš, J; Přikrylová Vranová, H; Klosová, J; Sládková, V; Doláková, J; Zapletalová, J; Kaňovský, P

    2015-02-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue. PMID:24894698

  11. High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids

    PubMed Central

    Peirouvi, T.; Yekani, F.; Azarnia, M.; Massumi, M.

    2015-01-01

    Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic cerebrospinal fluid (E-CSF) including E13.5, E17-CSF and the adult cerebrospinal fluid (A-CSF), all extracted from rats. CSF samples were selected based on their effects on cell behavioral parameters. Primary cell culture was performed in the presence of either normal or high levels of KCL in a culture medium. High levels of KCL cause cell depolarization, and thus the activation of quiescent NSCs. Results from immunocytochemistry (ICC) and semi-quantitative RT-PCR (sRT-PCR) techniques showed that in E-CSF-treated groups, neuronal differentiation increased (E17>E13.5). In contrast, A-CSF decreased and increased neuronal and astroglial differentiations, respectively. Cell survivability and/or proliferation (S/P), evaluated by an MTT assay, increased by E13.5 CSF, but decreased by both E17 CSF and A-CSF. Based on the results, it is finally concluded that adult rat hippocampal proliferative cells are not restricted progenitors but rather show high plasticity in neuronal/astroglial differentiation according to the effects of CSF samples. In addition, using high concentrations of KCL in the primary cell culture led to an increase in the number of NSCs, which in turn resulted in the increase in neuronal or astroglial differentiations after CSF treatment. PMID:27175157

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

    PubMed

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

    2015-08-01

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

  13. Cerebrospinal fluid constituents collected at the atlanto-occipital site of xylazine hydrochloride sedated, healthy 8-week-old Holstein calves.

    PubMed Central

    St Jean, G; Yvorchuk-St Jean, K; Anderson, D E; Moore, W E

    1997-01-01

    Cerebrospinal fluid (CSF) collected at the atlanto-occipital site and serum were obtained from 10 male, 8-week-old, Holstein calves after sedation with xylazine hydrochloride. Glucose, creatine kinase, alkaline phosphatase, urea nitrogen, creatinine, sodium, potassium, chloride, calcium, phosphorus, total protein, and albumin were determined in serum and CSF. Optical characteristics, specific gravity, total red blood cell and nucleated cell counts and differentials were also evaluated in the CSF. Additionally, CSF protein electrophoresis and immunoglobulin concentrations were determined. Then, albumin quotients (AQ) were derived. Erythrocytes were observed in 9 of 10 CSF samples. Total nucleated cell counts ranged from 0-10 cells x 10(6)/L with a mean of 3 cells x 10(6)/L. Differential nucleated cell count in the CSF consisted primarily of lymphocytes/small mononuclear cells (57%), fewer monocytes/ large mononuclear cells (38%), and scant neutrophils (4%) and eosinophils (0.05%). The concentration of sodium (134 to 139 mEq/L) was similar to that of serum, but the concentration of potassium (2.8 to 3 mEq/L) was lower than that of serum. Creatine kinase activity (0 to 4 U/L) of CSF was markedly lower than serum activity. The CSF glucose concentration was approximately 80% of the serum value. Cerebrospinal fluid total protein concentration determined by electrophoresis ranged from 110 to 330 mg/L with a mean of 159 mg/L. Cerebrospinal fluid albumin ranged from 48 to 209 mg/L with a mean of 86 mg/L. In all CSF samples, radial immunodiffusion of unaltered CSF and concentrated CSF (four-fold concentration) revealed quantities undetectable by the present techniques in which the lowest standard values for IgG1, IgG, and IgM determinations was 70 mg/L and IgG2 was 30 mg/L. The albumin quotient ranged from 0.15 to 0.65 with a mean of 0.25. Based on the results of this study, CSF may be collected at the atlanto-occipital site safely and efficiently in calves, and reported

  14. Selenium speciation in paired serum and cerebrospinal fluid samples of sheep.

    PubMed

    Humann-Ziehank, Esther; Ganter, Martin; Michalke, Bernhard

    2016-01-01

    This study was performed to characterise selenium (Se) and Se species in cerebrospinal fluid (CSF) of sheep and its relation to the respective Se concentrations in serum. Paired samples from 10 adult sheep were used for the study. Five sheep were fed a diet with a marginal Se concentration of <0.05mg Se/kg diet dry weight (dw, Se(-)), and five animals were fed the same diet supplemented with sodium selenite revealing a concentration of 0.2mg Se/kg diet dw (Se(+)). The feeding strategy was conducted for two years; The results on metabolic effects were published previously. At the end of the feeding period, paired samples of serum and CSF were collected and analysed using ion exchange chromatography inductively coupled plasma-dynamic reaction cell-mass spectrometry (IEC-ICP-DRC-MS) technique for total Se concentration and concentrations of Se species. Albumin concentrations were analysed additionally. The feeding strategy caused significant differences (p<0.01) in serum Se concentrations with 33.1±5.11μg Se/l in the Se(-) group and 96.5±18.3μg Se/l in the Se(+) group, respectively. The corresponding total Se concentrations in CSF were 4.38±1.02μg Se/l and 6.13±1.64μg Se/l in the Se(-) and the Se(+) group, respectively, missing statistical significance (p=0.077). IEC-ICP-DRC-MS technique was able to differentiate the Se species selenoprotein P-bound Se (SePP), selenomethionine, glutathione peroxidase-bound Se (Se-GPx), selenocystine, thioredoxin reductase-bound Se, ovine serum albumin-bound Se (Se-OSA), SeIV and SeVI in ovine serum and CSF. Quantitatively, SePP is the main selenoprotein in ovine serum followed by Se-GPx. The CSF/blood ratio of albumin (QAlbumin) reflected a physiological function of the blood-CSF barrier in all sheep. QSe-species were higher than QAlbumin both feeding groups, supporting the hypothesis of local production of Se species in the brain. Significant positive regression lines for CSF vs. serum were found for albumin and Se-OSA only

  15. Turnover rate of cerebrospinal fluid in female sheep: changes related to different light-dark cycles

    PubMed Central

    Thiéry, Jean-Claude; Lomet, Didier; Bougoin, Sylvain; Malpaux, Benoit

    2009-01-01

    Background Sheep are seasonal breeders. The key factor governing seasonal changes in the reproductive activity of the ewe is increased negative feedback of estradiol at the level of the hypothalamus under long-day conditions. It has previously been demonstrated that when gonadotropin secretions are inhibited during long days, there is a higher concentration of estradiol in the cerebrospinal fluid (CSF) than during short days. This suggests an involvement of the CSF and choroid plexus in the neuroendocrine regulatory loop, but the mechanisms underlying this phenomenon remain unknown. One possible explanation of this difference in hormonal content is an effect of concentration or dilution caused by variations in CSF secretion rate. The aim of this study was thus to investigate changes in the CSF turnover rate related to light-dark cycles. Methods The turnover rate of the CSF was estimated by measuring the time taken for the recovery of intraventricular pressure (IVP) after removal of a moderate volume (0.5 to 2 ml) of CSF (slope in mmHg/min). The turnover rate was estimated three times in the same group of sheep: during a natural period of decreasing day-length corresponding to the initial period when gonadotropin activity is stimulated (SG1), during a long-day inhibitory period (IG), and finally during a short-day stimulatory period (SG2). Results The time taken and the speed of recovery of initial IVP differed between groups: 8 min 30 sec, 0.63 ± 0.07 mmHg/min(SG1), 11 min 1 sec, 0.38 ± 0.06 mmHg/min (IG) and 9 min 0 sec, 0.72 ± 0.15 mmHg/min (SG2). Time changes of IVP differed between groups (ANOVA, p < 0.005, SG1 different from IG, p < 0.05). The turnover rate in SG2: 183.16 ± 23.82 μl/min was not significantly different from SG1: 169. 23 ± 51.58 μl/min (Mann-Whitney test, p = 0.41), but was significantly different from IG: 71.33 ± 16.59 μl/min (p = 0.016). Conclusion This study shows that the turnover rate of CSF in ewes changes according to the light

  16. Rapid diagnosis of experimental meningitis by bacterial heat production in cerebrospinal fluid

    PubMed Central

    Trampuz, Andrej; Steinhuber, Andrea; Wittwer, Matthias; Leib, Stephen L

    2007-01-01

    Background Calorimetry is a nonspecific technique which allows direct measurement of heat generated by biological processes in the living cell. We evaluated the potential of calorimetry for rapid detection of bacterial growth in cerebrospinal fluid (CSF) in a rat model of bacterial meningitis. Methods Infant rats were infected on postnatal day 11 by direct intracisternal injection with either Streptococcus pneumoniae, Neisseria meningitidis or Listeria monocytogenes. Control animals were injected with sterile saline or heat-inactivated S. pneumoniae. CSF was obtained at 18 hours after infection for quantitative cultures and heat flow measurement. For calorimetry, 10 μl and 1 μl CSF were inoculated in calorimetry ampoules containing 3 ml trypticase soy broth (TSB). Results The mean bacterial titer (± SD) in CSF was 1.5 ± 0.6 × 108 for S. pneumoniae, 1.3 ± 0.3 × 106 for N. meningitidis and 3.5 ± 2.2 × 104 for L. monocytogenes. Calorimetric detection time was defined as the time until heat flow signal exceeded 10 μW. Heat signal was detected in 10-μl CSF samples from all infected animals with a mean (± SD) detection time of 1.5 ± 0.2 hours for S. pneumoniae, 3.9 ± 0.7 hours for N. meningitidis and 9.1 ± 0.5 hours for L. monocytogenes. CSF samples from non-infected animals generated no increasing heat flow (<10 μW). The total heat was the highest in S. pneumoniae ranging from 6.7 to 7.5 Joules, followed by L. monocytogenes (5.6 to 6.1 Joules) and N. meningitidis (3.5 to 4.4 Joules). The lowest detectable bacterial titer by calorimetry was 2 cfu for S. pneumoniae, 4 cfu for N. meningitidis and 7 cfu for L. monocytogenes. Conclusion By means of calorimetry, detection times of <4 hours for S. pneumoniae and N. meningitidis and <10 hours for Listeria monocytogenes using as little as 10 μl CSF were achieved. Calorimetry is a new diagnostic method allowing rapid and accurate diagnosis of bacterial meningitis from a small volume of CSF. PMID:17927816

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

    Wibroe, Elisabeth A.; Yri, Hanne M.; Jensen, Rigmor H.; Wibroe, Morten A.; Hamann, Steffen

    2016-01-01

    Introduction Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial fluid pressure (ICP) of unknown etiology. This study aims to investigate osmolality of cerebrospinal fluid (CSF) from patients with IIH. Methods We prospectively collected CSF from individuals referred on suspicion of IIH from 2011–2013. Subjects included as patients fulfilled Friedman and Jacobson’s diagnostic criteria for IIH. Individuals in whom intracranial hypertension was refuted were included as controls. Lumbar puncture with ICP measurement was performed at inclusion and repeated for patients after three months of treatment. Osmolality was measured with a Vapor Pressure Osmometer. Results We collected 90 CSF samples from 38 newly diagnosed patients and 28 controls. At baseline 27 IIH-samples and at 3 months follow-up 35 IIH-samples were collected from patients. We found no significant differences in osmolality between 1) patients at baseline and controls (p = 0. 86), 2) patients at baseline and after 3 months treatment (p = 0.97), and 3) patients with normalized pressure after 3 months and their baseline values (p = 0.79). Osmolality in individuals with normal ICP from 6–25 cmH2O (n = 41) did not differ significantly from patients with moderately elevated ICP from 26–45 cmH2O (n = 21) (p = 0.86) and patients with high ICP from 46–70 cmH2O (n = 4) (p = 0.32), respectively. There was no correlation between osmolality and ICP, BMI, age and body height, respectively. Mean CSF osmolality was 270 mmol/kg (± 1 SE, 95% confidence interval 267–272) for both patients and controls. Conclusions CSF osmolality was normal in patients with IIH, and there was no relation to treatment, ICP, BMI, age and body height. Mean CSF osmolality was 270 mmol/kg and constitutes a reference for future studies. Changes in CSF osmolality are not responsible for development of IIH. Other underlying pathophysiological mechanisms must be searched. PMID:26808050

  19. [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

  20. Cerebral venous overdrainage: an under-recognized complication of cerebrospinal fluid diversion.

    PubMed

    Barami, Kaveh

    2016-09-01

    Understanding the altered physiology following cerebrospinal fluid (CSF) diversion in the setting of adult hydrocephalus is important for optimizing patient care and avoiding complications. There is mounting evidence that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. An evolved mechanism acting at the cortical bridging veins, known as the "Starling resistor," prevents overdrainage of cranial venous blood with upright positioning. This protective mechanism can become nonfunctional after CSF diversion, which can result in posture-related cerebral venous overdrainage through the cranial venous outflow tracts, leading to pathological states. This review article summarizes the relevant anatomical and physiological bases of the relationship between the craniospinal venous and CSF compartments and surveys complications that may be explained by the cerebral venous overdrainage phenomenon. It is hoped that this article adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients. PMID:27581321

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

    PubMed

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

    2013-12-01

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

  2. 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. PMID:25771509

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

    PubMed

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

    2015-07-01

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

  4. Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis.

    PubMed

    Arbeille, Elise; Reynaud, Florie; Sanyas, Isabelle; Bozon, Muriel; Kindbeiter, Karine; Causeret, Frédéric; Pierani, Alessandra; Falk, Julien; Moret, Frédéric; Castellani, Valérie

    2015-01-01

    The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones. PMID:25721514

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

    PubMed Central

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

    2006-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS. PMID:16313519

  6. Broadening the clinical spectrum: unusual presentation of spontaneous cerebrospinal fluid hypovolemia. Case report.

    PubMed

    Nowak, Dennis A; Rodiek, Sven-Olaf; Zinner, Jürgen; Guhlmann, Albrecht; Topka, Helge

    2003-04-01

    The syndrome of spontaneous intracranial hypotension is characterized by orthostatic headaches in conjunction with reduced cerebrospinal fluid (CSF) pressure or CSF volume, and characteristic magnetic resonance (MR) imaging findings. A 50-year-old man presented with a 1-year history of paroxysmal ataxia of gait and short attacks of blurred vision when he stood up from a recumbent position and began to walk. Orthostatic headache was not a feature of his clinical presentation. Magnetic resonance images of the brain revealed diffuse enhancement of the dura mater and hygromas over both cerebral convexities. Magnetic resonance images of the spine demonstrated dilated cervical epidural veins and dilation of the perimedullary veins. Radionuclide cisternography identified a CSF leakage that was localized to the T12-L1 level on subsequent myelograms and on computerized tomography scans obtained after the myelograms. An epidural blood patch was administered and visualized with tungsten powder. The patient's clinical symptoms and sites of disease on imaging completely resolved. The unusual clinical presentation in this case--paroxysmal ataxia of gait, lack of orthostatic headaches, and dilated epidural and perimedullary venous plexus--supports a recently noted broadening of both the clinical and imaging characteristics of spontaneous intracranial hypovolemia. PMID:12691420

  7. Ethmoidal encephalocele associated with cerebrospinal fluid fistula: indications and results of mini-invasive transnasal approach.

    PubMed

    Fraioli, Mario Francesco; Umana, Giuseppe Emanuele; Fiorucci, Giulia; Fraioli, Chiara

    2014-03-01

    Anterior skull base defects with encephalocele in adults are quite rare and can be a cause of spontaneous rhinoliquorrhea; however, cerebrospinal fluid (CSF) fistula can be not rarely misdiagnosed for several months or years. Five adult patients affected by ethmoidal encephalocele with CSF fistula were treated in our institute from 2006 through to 2011. Onset of clinical history was represented by rhinoliquorrhea, which was precociously recognized in only 1 patient; in the other 4, it was misdiagnosed for a period ranging from 11 months to 5 years. After clinical diagnosis of CSF fistula and after brain magnetic resonance imaging, ethmoidal encephalocele was evident in all patients; preoperative study was completed by spiral computed tomography scan, to clearly identify the skull base bone defect. All patients were operated on by transsphenoidal endonasal endoscope-assisted microsurgical approach through 1 nostril. The herniated brain was coagulated and removed, and reconstruction of cranial base was performed. Postoperative rhinoliquorrhea or other complications did not occur in any patient at short and late follow-up. All patients were discharged after a few days. Endonasal endoscope-assisted microsurgical approach was effective in exposing and repairing the ethmoidal bone defect; tridimensional vision and wide lateral and superior exposition of the operative field were possible in each patient, thanks to the use of microscope and angulated endoscope. PMID:24514886

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

    PubMed

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

    2013-02-01

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

  9. Derivative spectrophotometric analysis of cerebrospinal fluid for the detection of a ruptured cerebral aneurysm

    NASA Astrophysics Data System (ADS)

    Bhadri, P. R.; Majumder, A.; Morgan, C. J.; Pyne, G. J.; Zuccarello, M.; Jauch, E.; Wagner, K. R.; Clark, J. F.; Caffery, J., Jr.; Beyette, Fred R., Jr.

    2003-11-01

    A cerebral aneurysm is a weakened portion of an artery in the brain. When a cerebral aneurysm ruptures, a specific type of bleeding known as a subarachnoid hemorrhage (SAH) occurs. No test exists currently to screen people for the presence of an aneurysm. The diagnosis of a SAH is made after an aneurysm ruptures, and the literature indicates that nearly one-third of patients with a SAH are initially misdiagnosed and subjected to the risks associated with aneurysm re-rupture. For those individuals with a suspected SAH, a computerized tomography (CT) scan of the brain usually demonstrates evidence of the bleeding. However, in a considerable portion of people, the CT scan is unable to detect the blood that has escaped from the blood vessel. For circumstances when a SAH is suspected despite a normal CT scan, physicians make the diagnosis of SAH by performing a spinal tap. A spinal tap uses a needle to sample the cerebrospinal fluid (CSF) collected from the patient"s back; CSF is tainted with blood after the aneurysm ruptures. To distinguish between a common headache and a SAH, a fast and an effective solution is required. We describe the development of an effective detection system integrating hardware and a powerful software interface solution. Briefly, CSF from the patient is aspirated and excited with an appropriate wavelength of light. The software employs spectrophotometric analysis of the output spectra and lays the foundation for the development of portable and user-friendly equipment for detection of a ruptured cerebral aneurysm.

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

    PubMed

    Wang, Lucy Y; Murphy, Richard R; Hanscom, Brett; Li, Ge; Millard, Steven P; Petrie, Eric C; Galasko, Douglas R; Sikkema, Carl; Raskind, Murray A; Wilkinson, Charles W; Peskind, Elaine R

    2013-10-01

    Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21-100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p = 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p = 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p = 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment. PMID:23639207

  11. Thyroid Autoantibodies in the Cerebrospinal Fluid of Subjects with and without Thyroid Disease: Implications for Hashimoto's Encephalopathy

    PubMed Central

    Ilias, Ioannis; Karagiorga, Vasiliki; Paraskevas, George; Bougea, Anastasia; Bourbouli, Mara; Pappa, Athina; Nikopoulou, Stamatina; Kapaki, Elisabeth

    2015-01-01

    Introduction. Plasma antithyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies (anti-Tg) are widely used in the diagnosis of autoimmune thyroiditis. No research has compared anti-TPO and anti-Tg both in plasma and cerebrospinal fluid (CSF) of healthy individuals vis-à-vis patients with thyroid disease. Methods. We measured anti-TPO and anti-Tg antibodies in plasma and CSF in nine subjects (mean age ± SD: 73 ± 6 years) with hypothyroidism and nine subjects (mean age ± SD: 73 ± 8 years) without thyroid disease. Results. The concentration of anti-TPO autoantibodies in CSF was very low compared to plasma in both subjects with thyroid and without thyroid disease (P = 0.007). CSF anti-Tg autoantibodies titers were very low compared to the plasma in subjects with thyroid disease (P = 0.004), whereas, in subjects without thyroid disease, this difference did not reach statistical significance (P = 0.063). Conclusions. Thyroid autoantibodies levels were low in plasma and CSF; we did not observe any transfer of thyroid autoantibodies from the peripheral blood to the CSF. Therefore, regarding Hashimoto's encephalopathy, where elevated antithyroid autoantibodies are often measured in blood, it is more likely that thyroiditis and encephalopathy represent nonspecific, but distinct, events of an aggressive immune system. PMID:26798549

  12. Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections†

    PubMed Central

    Nau, Roland; Sörgel, Fritz; Eiffert, Helmut

    2010-01-01

    Summary: The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable. PMID:20930076

  13. 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

  14. Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus.

    PubMed

    Nakajima, Madoka; Miyajima, Masakazu; Ogino, Ikuko; Akiba, Chihiro; Sugano, Hidenori; Hara, Takeshi; Fusegi, Keiko; Karagiozov, Kostadin; Arai, Hajime

    2015-10-15

    The prognosis of cognitive improvement after cerebrospinal fluid (CSF) shunting in idiopathic normal pressure hydrocephalus (iNPH) remains uncertain, with no reports on CSF biomarkers related to long-term cognitive prognosis. We performed a preliminary study of CSF biomarker protein levels for cognitive outcome prognostication of two-year outcomes after shunt treated iNPH in 36 patients (13 women) with a median age of 75years (IQR 69-78). CSF biomarkers included soluble amyloid precursor proteins (sAPP, sAPPα, sAPPβ), amyloid β (Aβ)1-38, Aβ1-42 and phosphorylated tau (p-tau), lipocalin-type prostaglandin D synthase (L-PGDS)/β-trace, and cystatin C. The results clearly showed that p-tau levels (sensitivity of 71.4%, specificity of 77.8%, cut-off value of 22.0pg/mL), Aβ1-38/Aβ1-42 ratio (77.8%, 81%, 3.58), and the Aβ1-42/p-tau ratio (76%, 72.7%, 14.6) in preoperative CSF have the potential to determine postoperative prognosis. Improved cognition may be associated with the improvement in CSF circulation after LPS, which likely induces cystatin C and L-PGDS and switches synthesis from Aβ1-42 to Aβ1-38. PMID:26169158

  15. Predominance of Vgamma9/Vdelta2 T lymphocytes in the cerebrospinal fluid of children with tuberculous meningitis: reversal after chemotherapy.

    PubMed Central

    Dieli, F.; Sireci, G.; Di Sano, C.; Champagne, E.; Fourniè, J. J.; Salerno, J. I.

    1999-01-01

    BACKGROUND: We analyzed the gammadelta T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children. MATERIALS AND METHODS: Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vgamma9/Vdelta2 T cells assessed by FACS analysis. Vgamma9/Vdelta2 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and IL-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. Vdelta2(D)Jdelta junctional sequence length was assessed by PCR. RESULTS: The repertoire of gammadelta T cells from the CSF of TBM patients was characterized by the predominance of Vgamma9/Vdelta2 T lymphocytes, which accounted for >80% of gammadelta T cells. Vgamma9/Vdelta2 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-gamma and TNF-alpha. The in vitro expansion of Vgamma9/Vdelta2 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and similarly, the proportion of ex vivo unstimulated Vgamma9/Vdelta2 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. Vdelta2 CDR3 TCR analysis showed that the remaining Vdelta2 cells in the CSF of TBM patients were still polyclonal. CONCLUSIONS: These findings are consistent with an involvement of Vgamma9/Vdelta2 T cells in TBM. http://link. springer-ny.com/link/service/journals/00020/bibs/5n5p301. html Images Fig. 3 PMID:10390546

  16. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.

    PubMed

    Severance, Emily G; Gressitt, Kristin L; Alaedini, Armin; Rohleder, Cathrin; Enning, Frank; Bumb, J Malte; Müller, Juliane K; Schwarz, Emanuel; Yolken, Robert H; Leweke, F Markus

    2015-02-01

    Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R(2)=0.34-0.55, p⩽0.0001; controls R(2)=0.05-0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p⩽0.001-0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature. PMID:25241021

  17. Volumetric analysis of cerebrospinal fluid and brain parenchyma in a patient with hydranencephaly and macrocephaly – case report

    PubMed Central

    Radoš, Milan; Klarica, Marijan; Mučić-Pucić, Branka; Nikić, Ines; Raguž, Marina; Galkowski, Valentina; Mandić, Dora; Orešković, Darko

    2014-01-01

    The aim of this study was to perform for the first time the intracranial volumetric analysis of cerebrospinal fluid (CSF) and brain parenchyma in the supratentorial and infratentorial space in a 30-year-old female patient with hydranencephaly and macrocephaly. A head scan performed using a 3T magnetic resonance was followed by manual segmentation of the brain parenchyma and CSF on T2 coronal brain sections. The volume of CSF and brain parenchyma was measured separately for the supratentorial and infratentorial space. The total volume of the intracranial space was 3645.5 cm3. In the supratentorial space, the volume of CSF was 3375.2 cm3 and the volume of brain parenchyma was 80.3 cm3. In the infratentorial space, the volume of CSF was 101.3 cm3 and the volume of the brain parenchyma was 88.7 cm3. In the supratentorial space, there was severe malacia of almost all brain parenchyma with no visible remnants of the choroid plexuses. Infratentorial structures of the brainstem and cerebellum were hypoplastic but completely developed. Since our patient had no choroid plexuses in the supratentorial space and no obstruction between dural sinuses and CSF, development of hydrocephalus and macrocephaly cannot be explained by the classic hypothesis of CSF physiology with secretion, unidirectional circulation, and absorption as its basic postulates. However, the origin and turnover of the enormous amount of intracranial CSF volume, at least 10-fold larger than normal, and the mechanisms of macroencephaly development could be elucidated by the new hypothesis of CSF physiology recently published by our research team. PMID:25165052

  18. Volumetric analysis of cerebrospinal fluid and brain parenchyma in a patient with hydranencephaly and macrocephaly--case report.

    PubMed

    Radoš, Milan; Klarica, Marijan; Mučić-Pucić, Branka; Nikić, Ines; Raguž, Marina; Galkowski, Valentina; Mandić, Dora; Orešković, Darko

    2014-08-28

    The aim of this study was to perform for the first time the intracranial volumetric analysis of cerebrospinal fluid (CSF) and brain parenchyma in the supratentorial and infratentorial space in a 30-year-old female patient with hydranencephaly and macrocephaly. A head scan performed using a 3T magnetic resonance was followed by manual segmentation of the brain parenchyma and CSF on T2 coronal brain sections. The volume of CSF and brain parenchyma was measured separately for the supratentorial and infratentorial space. The total volume of the intracranial space was 3645.5 cm3. In the supratentorial space, the volume of CSF was 3375.2 cm3 and the volume of brain parenchyma was 80.3 cm3. In the infratentorial space, the volume of CSF was 101.3 cm3 and the volume of the brain parenchyma was 88.7 cm3. In the supratentorial space, there was severe malacia of almost all brain parenchyma with no visible remnants of the choroid plexuses. Infratentorial structures of the brainstem and cerebellum were hypoplastic but completely developed. Since our patient had no choroid plexuses in the supratentorial space and no obstruction between dural sinuses and CSF, development of hydrocephalus and macrocephaly cannot be explained by the classic hypothesis of CSF physiology with secretion, unidirectional circulation, and absorption as its basic postulates. However, the origin and turnover of the enormous amount of intracranial CSF volume, at least 10-fold larger than normal, and the mechanisms of macroencephaly development could be elucidated by the new hypothesis of CSF physiology recently published by our research team. PMID:25165052

  19. Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study

    PubMed Central

    Simon, Tamara D.; Butler, Jerry; Whitlock, Kathryn B.; Browd, Samuel R.; Holubkov, Richard; Kestle, John R.W.; Kulkarni, Abhaya V.; Langley, Marcie; Limbrick, David D.; Mayer-Hamblett, Nicole; Tamber, Mandeep; Wellons, John C.; Whitehead, William E.; Riva-Cambrin, Jay

    2014-01-01

    Objective To quantify the extent to which revision(s) of cerebrospinal fluid (CSF) shunt are associated with increased risk of CSF shunt infection, after adjusting for patient factors that may contribute to infection risk. Study design We used the HCRN registry to assemble a large prospective six center cohort of 1,036 children undergoing initial CSF shunt placement between April 2008 and January 2012. The primary outcome of interest was first CSF shunt infection. Data for initial CSF shunt placement and all subsequent CSF shunt revisions prior to first CSF shunt infection, where applicable, were obtained. The risk of first infection was estimated using a multivariable Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HR) with 95% confidence intervals (CI). Results Of the 102 children who developed first infection within 12 months of placement, 33 (32%) followed one or more CSF shunt revisions. Baseline factors independently associated with risk of first infection included: gastrostomy tube (HR 2.0, 95% CI: 1.1, 3.3), age 6–12 months (HR 0.3, 95% CI: 0.1, 0.8), and prior neurosurgery (HR 0.4, 95% CI: 0.2, 0.9). After controlling for baseline factors, infection risk was most significantly associated with the need for revision (1 revision vs. none, HR 3.9, 95% CI: 2.2, 6.5; ≥2 revisions, HR 13.0, 95% CI: 6.5, 24.9). Conclusions This study quantifies the elevated risk of infection associated with shunt revisions observed in clinical practice. To reduce risk of infection risk further work should optimize revision procedures. PMID:24661340

  20. Large neutral amino acids levels in primate cerebrospinal fluid do not confirm competitive transport under baseline conditions.

    PubMed

    Bongiovanni, Rodolfo; Mchaourab, Ali S; McClellan, Frances; Elsworth, John; Double, Manda; Jaskiw, George E

    2016-10-01

    In rodents, transport of large neutral amino acids (LNAAs) across the blood brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier is mediated by high affinity carriers. Net brain LNAA levels are thought to be determined mainly by this competitive transport from plasma. Since the affinity for LNAA transport at the BBB in primates is considerably higher than in rodents, brain influx and by extension LNAA brain levels, should be even more dependent on competitive transport. Given that LNAA levels in CSF and brain interstitial fluid are usually similar, we analyzed serum and CSF of fasted subjects (n=24) undergoing spinal anesthesia and calculated brain influx and transporter occupancy using a conventional model of transport. Despite predicted near-full transporter saturation (99.7%), correlations between CSF levels and brain influx were modest, limited to tyrosine (r=0.60, p<0.002) and tryptophan (r=0.50, p<0.01) and comparable to correlations between CSF and serum levels. We also analyzed serum and CSF in (n=5) fasted vervet monkeys. Tyrosine and phenylalanine levels in CSF were positively correlated with those in serum, but correlations with calculated brain influx, which takes competition into account, were weaker or absent. We conclude that in primates i) baseline CSF LNAA levels do not confirm competitive transport, ii) brain LNAA levels should not be estimated on the basis of serum indices alone. This has implications for amino acid challenge studies and for neuropsychiatric disorders associated with dysregulated LNAA transport in which quantitative information about brain LNAA levels is needed. PMID:27521685

  1. Postmortem serotonin levels in cerebrospinal and pericardial fluids with regard to the cause of death in medicolegal autopsy.

    PubMed

    Quan, Li; Ishikawa, Takaki; Hara, Junpei; Michiue, Tomomi; Chen, Jian-Hua; Wang, Qi; Zhu, Bao-li; Maeda, Hitoshi

    2011-03-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in the central nervous system (CNS) and a smooth muscle regulator in the cardiovascular and gastrointestinal systems. The present study investigated postmortem 5-HT levels in cerebrospinal fluid (CSF) and pericardial fluid (PCF) with regard to the cause of death in serial medicolegal autopsy cases within 48 h postmortem (n=351, >20 years of age). CSF and PCF 5-HT slightly increased during the postmortem period (r=0.298 and 0.253, respectively, p<0.001), showing no gender-related difference. The CSF level decreased depending on the subject age (r=0.497, p<0.001); however, the CSF and PCF levels showed similar findings with regard to the cause of death: these levels were significantly higher for sedative-hypnotic drug intoxication and hyperthermia (heat stroke), but lower for blunt head injury and hypothermia (cold exposure); the cutoff value was estimated as 25.5 ng/ml and 5.0 ng/ml, respectively. For other cause of death groups, some cases showed a higher level. These findings suggest elevations in CSF and PCF 5-HT levels due to systemic toxic or hyperthermic neuronal dysfunction, and systemic stress responses to trauma without CNS involvement. PMID:21185763

  2. 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. PMID:24394344

  3. Lower levels of cerebrospinal fluid amyloid beta (Abeta) in non-demented Indian controls.

    PubMed

    Subramanian, Sarada; Sandhyarani, Boya; Shree, A N Divya; Murthy, K Krishna; Kalyani, K; Kumar, S Praveen; Pradeep; Noone, Mohin Jeslie; Taly, A B

    2006-10-23

    Prevalence of Alzheimer's disease in Indian population is lower than in developed countries. To determine whether limitation of amyloid beta (Abeta) concentration may be responsible for lower rate of incidence, we measured the levels of Abeta in cerebrospinal fluid (CSF) collected from 72 non-demented individuals ranging in the age from 20 years to 65 years. These samples were segregated into three groups ranging from 20-35 years, 36-50 years and 51-65 years of age. Levels of Abeta could be detected in all the age groups and they were much lower than the values reported in literature from the developed countries. No significant difference in the average level of Ass was observed with increase in age. PMID:16978775

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

    PubMed

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

    2016-08-01

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

  5. Stability of Progranulin Under Pre-Analytical Conditions in Serum and Cerebrospinal Fluid.

    PubMed

    Willemse, Eline A J; Durieux-Lu, Sisi; van der Flier, Wiesje M; Pijnenburg, Yolande A L; de Jonge, Robert; Teunissen, Charlotte E

    2016-04-21

    Progranulin (PGRN) levels in blood and cerebrospinal fluid (CSF) are increasingly studied as potential markers for neurodegenerative disorders. We aimed to 1) characterize two commercially available PGRN ELISAs on several assay validation parameters, 2) assess the stability of PGRN in serum and CSF under pre-analytical conditions, and 3) compare stability in the two assays. Intra- and inter-assay variation, inter-lot variation, linearity, lower limit of detection, and kit correlations were assessed for the Adipogen and R&D PGRN ELISA kits. Blood and serum samples were experimentally exposed to ≤9 freeze/thaw cycles, delayed processing for ≤24 h at room temperature and 4°C, and to temperature stability tests for ≤3 weeks at -20°C, 4°C, room temperature, and 37°C. Both commercial PGRN ELISA kits showed acceptable ranges for intra- and inter-assay variation, where the R&D kit performed more accurate than the Adipogen kit, especially for inter-assay variation (intra-assay serum: 6.7 and 8.3%, respectively; inter-assay serum: 9.2 and 21.0%; intra-assay CSF: 3.6 and 12.0%; inter-assay CSF: 16.0 and 44.5%). Absolute serum PGRN concentrations were 1.9-fold higher in Adipogen than R&D (p < 0.001) and strongly correlated between both kits (ρ= 0.86, p < 0.0001) and CSF PGRN levels were on the borderline of detection in both kits. PGRN was typically stable under all pre-analytical conditions addressed, although two weeks at 37°C resulted in decreased PGRN concentrations in CSF, only when using the Adipogen kit. These results support further examination of PGRN as a potential marker in neurodegenerative diseases, since PGRN is stable in serum and CSF and can be measured using ELISA kits from several providers. PMID:27104901

  6. An Empirical Approach to the Diagnosis and Treatment of Cerebrospinal Fluid Rhinorrhoea: An Optimised Method for Developing Countries

    PubMed Central

    SAFAVI, Ali; Safavi, Amir Ali; Jafari, Rozita

    2014-01-01

    Background: We aimed to test a new approach for repairing cerebrospinal fluid (CSF) leaks and to determine the demographic, diagnostic, and treatment factors associated with the successful management of intracranial complication. Owing to the high frequency of endoscopic surgeries and the low cost of medical care in Iran, we decided to report our experience of reconstruction after CSF leaks. Methods: We retrospectively reviewed our experience in the diagnosis and management of CSF rhinorrhoea in Iran between 2005 and 2012. The locations of all pre-repair leaks were identified using simple, readily available methods. The follow-up time ranged from 2 to 72 months. Results: Of the 37 participants, 59.5% were men and the mean age was 33 years. The success rate was 86.1%, and the most common aetiological factor was trauma (57%). The most common location was the ethmoidal fovea (45.9%), followed by the sphenoid sinus (24.3%), the cribriform plate (13.5%), and the posterior table of the frontal sinus (5.4%). Conclusion: Medical care in Iran has considerable budget restrictions. This study advocates a practical method of treatment for patients in similar circumstances, with a success rate of 86.1% when compared to the 90.6% achieved with other techniques. Keywords: cerebrospinal fluid leak, endoscopic, intracranial pressure ICP PMID:25977632

  7. Quantitative evaluation of changes in gait after extended cerebrospinal fluid drainage for normal pressure hydrocephalus.

    PubMed

    Yang, Felix; Hickman, Thu-Trang; Tinl, Megan; Iracheta, Christine; Chen, Grace; Flynn, Patricia; Shuman, Matthew E; Johnson, Tatyana A; Rice, Rebecca R; Rice, Isaac M; Wiemann, Robert; Johnson, Mark D

    2016-06-01

    Idiopathic normal pressure hydrocephalus (iNPH) is characterized by gait instability, urinary incontinence and cognitive dysfunction. These symptoms can be relieved by cerebrospinal fluid (CSF) drainage, but the time course and nature of the improvements are poorly characterized. Attempts to prospectively identify iNPH patients responsive to CSF drainage by evaluating presenting gait quality or via extended lumbar cerebrospinal fluid drainage (eLCD) trials are common, but the reliability of such approaches is unclear. Here we combine eLCD trials with computerized quantitative gait measurements to predict shunt responsiveness in patients undergoing evaluation for possible iNPH. In this prospective cohort study, 50 patients presenting with enlarged cerebral ventricles and gait, urinary, and/or cognitive difficulties were evaluated for iNPH using a computerized gait analysis system during a 3day trial of eLCD. Gait speed, stride length, cadence, and the Timed Up and Go test were quantified before and during eLCD. Qualitative assessments of incontinence and cognition were obtained throughout the eLCD trial. Patients who improved after eLCD underwent ventriculoperitoneal shunt placement, and symptoms were reassessed serially over the next 3 to 15months. There was no significant difference in presenting gait characteristics between patients who improved after drainage and those who did not. Gait improvement was not observed until 2 or more days of continuous drainage in most cases. Symptoms improved after eLCD in 60% of patients, and all patients who improved after eLCD also improved after shunt placement. The degree of improvement after eLCD correlated closely with that observed after shunt placement. PMID:26775149

  8. Comparative Analysis of Cell-Associated HIV DNA Levels in Cerebrospinal Fluid and Peripheral Blood by Droplet Digital PCR

    PubMed Central

    de Oliveira, Michelli Faria; Gianella, Sara; Letendre, Scott; Scheffler, Konrad; Kosakovsky Pond, Sergei L.; Smith, Davey M.; Strain, Matt; Ellis, Ronald J.

    2015-01-01

    Background Measurement of HIV DNA-bearing cells in cerebrospinal fluid (CSF) is challenging because few cells are present. We present a novel application of the sensitive droplet digital (dd)PCR in this context. Methods We analyzed CSF cell pellets and paired peripheral blood mononuclear cells (PBMC) from 28 subjects, 19 of whom had undetectable HIV RNA (<48 copies/mL) in both compartments. We extracted DNA from PBMC using silica-based columns and used direct lysis on CSF cells. HIV DNA and the host housekeeping gene (RPP30) were measured in CSF and PBMC by (dd)PCR. We compared HIV DNA levels in virally-suppressed and-unsuppressed subgroups and calculated correlations between HIV DNA and RNA levels in both compartments using non-parametric tests. Results HIV DNA was detected in 18/28 (64%) CSF cell pellets, including 10/19 (53%) samples with undetectable HIV RNA. HIV DNA levels in CSF cell pellets were not correlated with RPP30 (p = 0.3), but correlated positively with HIV RNA in CSF (p = 0.04) and HIV DNA in PBMC (p = 0.03). Cellular HIV DNA in CSF was detected in comparable levels in HIV RNA-suppressed and unsuppressed subjects (p = 0.14). In contrast, HIV DNA levels in PBMC were significantly lower in HIV RNA-suppressed than in unsuppressed subjects (p = 0.014). Among subjects with detectable HIV DNA in both compartments, HIV DNA levels in CSF were significantly higher than in PBMC (p<0.001). Conclusions Despite low mononuclear cell numbers in CSF, HIV DNA was detected in most virally suppressed individuals. In contrast to PBMC, suppressive ART was not associated with lower HIV DNA levels in CSF cells, compared to no ART, perhaps due to poorer ART penetration, slower decay of HIV DNA, or enrichment of HIV DNA-bearing mononuclear cells into the CSF, compared to blood. Future studies should determine what fraction of HIV DNA is replication-competent in CSF leukocytes, compared to PBMC. PMID:26431315

  9. Cerebrospinal Fluid Hypocretin-1 (Orexin-A) Level Fluctuates with Season and Correlates with Day Length.

    PubMed

    Boddum, Kim; Hansen, Mathias Hvidtfelt; Jennum, Poul Jørgen; Kornum, Birgitte Rahbek

    2016-01-01

    The hypocretin/orexin neuropeptides (hcrt) are key players in the control of sleep and wakefulness evidenced by the fact that lack of hcrt leads to the sleep disorder Narcolepsy Type 1. Sleep disturbances are common in mood disorders, and hcrt has been suggested to be poorly regulated in depressed subjects. To study seasonal variation in hcrt levels, we obtained data on hcrt-1 levels in the cerebrospinal fluid (CSF) from 227 human individuals evaluated for central hypersomnias at a Danish sleep center. The samples were taken over a 4 year timespan, and obtained in the morning hours, thus avoiding impact of the diurnal hcrt variation. Hcrt-1 concentration was determined in a standardized radioimmunoassay. Using biometric data and sleep parameters, a multivariate regression analysis was performed. We found that the average monthly CSF hcrt-1 levels varied significantly across the seasons following a sine wave with its peak in the summer (June-July). The amplitude was 19.9 pg hcrt/mL [12.8-26.9] corresponding to a 10.6% increase in midsummer compared to winter. Factors found to significantly predict the hcrt-1 values were day length, presence of snow, and proximity to the Christmas holiday season. The hcrt-1 values from January were much higher than predicted from the model, suggestive of additional factors influencing the CSF hcrt-1 levels such as social interaction. This study provides evidence that human CSF hcrt-1 levels vary with season, correlating with day length. This finding could have implications for the understanding of winter tiredness, fatigue, and seasonal affective disorder. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation. PMID:27008404

  10. Cerebrospinal Fluid JC Virus Antibody Index for Diagnosis of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

    PubMed Central

    Warnke, Clemens; von Geldern, Gloria; Markwerth, Philipp; Dehmel, Thomas; Hoepner, Robert; Gold, Ralf; Pawlita, Michael; Kümpfel, Tania; Mäurer, Mathias; Stangel, Martin; Wegner, Florian; Hohlfeld, Reinhard; Straeten, Vera; Limmroth, Volker; Weber, Thomas; Hermsen, Derik; Kleinschnitz, Christoph; Hartung, Hans-Peter; Wattjes, Mike P.; Anders, Svenningson; Major, Eugene; Olsson, Tomas; Kieseier, Bernd C.; Adams, Ortwin

    2014-01-01

    Objective Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV) in the diagnosis of natalizumab-associated PML. Methods AIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published. Results Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5. Interpretation Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML. PMID:24729444

  11. A technique for cannulating the Cisterna magna and sampling cerebrospinal fluid from socially housed birds.

    PubMed

    Moore, M S; Kuenzel, W J; Mench, J A

    1994-04-01

    The measurement of central levels of neurochemicals is an important approach to the understanding of the neurophysiological basis of behavior patterns in animals. Previous studies have utilized central sampling techniques developed for individually housed animals. The purpose of this study was to develop a cannulation technique and a method for sampling cerebrospinal fluid (CSF) from socially housed birds to facilitate the study of the neurophysiological basis of social behaviors. The cannulation technique involved the surgical implantation of a 22-gauge concentric guide cannula into the cisterna magna of 16-wk-old, feed-restricted male broiler breeders (n = 6). Individual-specific coordinates and optimum angle and depth of implantation of the cannula were determined in order to place the cannula correctly in the designated site. Once implanted, the guide cannula proved to be unobtrusive and secure and did not attract aggressive pecking from other birds in the pen. Two methods of CSF sampling were then examined. The first method required the use of a push-pull perfusion pump to withdraw CSF at a rate of 1 to 2 microL/min. The second method (passive), which did not use a pump, involved simply removing a "dummy" cannula from the guide cannula to release the CSF, which was then collected with a glass Hamilton syringe. Samples ranging from 100 to 500 microL were collected using the passive method. The combination of the cannulation technique described and the passive sampling method proved to be the most simple, efficient, and reliable method for measuring central levels of neurochemicals in socially housed broiler breeder males. PMID:8202435

  12. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer's Disease in Human Cerebrospinal Fluid.

    PubMed

    Hendrickson, Ronald C; Lee, Anita Y H; Song, Qinghua; Liaw, Andy; Wiener, Matt; Paweletz, Cloud P; Seeburger, Jeffrey L; Li, Jenny; Meng, Fanyu; Deyanova, Ekaterina G; Mazur, Matthew T; Settlage, Robert E; Zhao, Xuemei; Southwick, Katie; Du, Yi; Holder, Dan; Sachs, Jeffrey R; Laterza, Omar F; Dallob, Aimee; Chappell, Derek L; Snyder, Karen; Modur, Vijay; King, Elizabeth; Joachim, Catharine; Bondarenko, Andrey Y; Shearman, Mark; Soper, Keith A; Smith, A David; Potter, William Z; Koblan, Ken S; Sachs, Alan B; Yates, Nathan A

    2015-01-01

    Disease modifying treatments for Alzheimer's disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001) and SME-2 (p = 0.0004) for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR), in AD were 21% (p = 0.039) and 17% (p = 0.026) lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic. PMID:26270474

  13. Cerebrospinal Fluid Hypocretin-1 (Orexin-A) Level Fluctuates with Season and Correlates with Day Length

    PubMed Central

    Boddum, Kim; Hansen, Mathias Hvidtfelt; Jennum, Poul Jørgen; Kornum, Birgitte Rahbek

    2016-01-01

    The hypocretin/orexin neuropeptides (hcrt) are key players in the control of sleep and wakefulness evidenced by the fact that lack of hcrt leads to the sleep disorder Narcolepsy Type 1. Sleep disturbances are common in mood disorders, and hcrt has been suggested to be poorly regulated in depressed subjects. To study seasonal variation in hcrt levels, we obtained data on hcrt-1 levels in the cerebrospinal fluid (CSF) from 227 human individuals evaluated for central hypersomnias at a Danish sleep center. The samples were taken over a 4 year timespan, and obtained in the morning hours, thus avoiding impact of the diurnal hcrt variation. Hcrt-1 concentration was determined in a standardized radioimmunoassay. Using biometric data and sleep parameters, a multivariate regression analysis was performed. We found that the average monthly CSF hcrt-1 levels varied significantly across the seasons following a sine wave with its peak in the summer (June—July). The amplitude was 19.9 pg hcrt/mL [12.8–26.9] corresponding to a 10.6% increase in midsummer compared to winter. Factors found to significantly predict the hcrt-1 values were day length, presence of snow, and proximity to the Christmas holiday season. The hcrt-1 values from January were much higher than predicted from the model, suggestive of additional factors influencing the CSF hcrt-1 levels such as social interaction. This study provides evidence that human CSF hcrt-1 levels vary with season, correlating with day length. This finding could have implications for the understanding of winter tiredness, fatigue, and seasonal affective disorder. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation. PMID:27008404

  14. Methodological aspects of ELISA analysis of thioredoxin 1 in human plasma and cerebrospinal fluid.

    PubMed

    Lundberg, Mathias; Curbo, Sophie; Reiser, Kathrin; Masterman, Thomas; Braesch-Andersen, Sten; Areström, Irene; Ahlborg, Niklas

    2014-01-01

    Thioredoxin-1 (Trx1) is a protein antioxidant involved in major cellular processes. Increased plasma levels of Trx1 have been associated with human diseases suggesting that Trx1 is a marker for oxidative stress with putative clinical use. However, the reported mean levels of Trx1 in the control cohorts vary a hundred-fold between studies (0.8-87 ng/ml), possibly due to methodological differences between the capture ELISA used in the different studies. The aim of this study was to investigate methodological aspects related to the ELISA measurement of Trx1. ELISAs utilizing different capture and detection combinations of antibodies to Trx1 and as well as recombinant human (rh) Trx1 standards from two sources were characterized. The different ELISAs were subsequently used to measure Trx1 in human plasma and cerebrospinal fluid samples (CSF) from healthy donors and from patients with various neurological diagnoses. The Trx1 standards differed in their content of monomeric and oligomeric Trx1, which affected the ELISAs composed of different antibody combinations. Thus, the levels of Trx1 determined in human plasma and CSF samples varied depending on the antibody used in the ELISAs and on the rhTrx1 standard. Furthermore, the relevance of preventing interference by heterophilic antibodies (HA) in human plasma and CSF was investigated. The addition of a HA blocking buffer to human samples drastically reduced the ELISA signals in many samples showing that HA are likely to cause false positive results unless they are blocked. In conclusion, the study shows that the design of a Trx1 ELISA in regards to antibodies and standards used has an impact on the measured Trx1 levels. Importantly, analyses of human plasma and CSF without preventing HA interference may obscure the obtained data. Overall, the results of this study are crucial for the improvement of future studies on the association of Trx1 levels with various diseases. PMID:25075746

  15. Increased Concentrations of Interleukin-33 in the Serum and Cerebrospinal Fluid of Patients with Multiple Sclerosis

    PubMed Central

    Jafarzadeh, Abdollah; Mahdavi, Roya; Jamali, Mitra; Hajghani, Hossain; Nemati, Maryam; Ebrahimi, Hossain-Ali

    2016-01-01

    Objectives Interleukin (IL)-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF) IL-33 concentrations in patients with multiple sclerosis (MS). Methods Blood specimens were obtained from 140 patients with MS (46 males and 94 females) with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females), who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. Results The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p<0.001 and p<0.050, respectively). The serum IL-33 concentrations were also significantly higher in newly diagnosed (untreated) patients and patients treated with methylprednisolone or with interferon-β and methylprednisolone compared to the healthy patient group (p<0.007, p<0.002, and p<0.010, respectively). Moreover, the serum IL-33 concentrations in patients with relapsing-remitting (RRMS), primary progressive (PPMS), and secondary progressive (SPMS) forms of the disease were significantly higher than in the healthy control group (p<0.006, p<0.001, and p<0.020, respectively). Conclusions Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-β plus methylprednisolone has no influence on IL-33 concentrations. PMID:26813806

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

    PubMed

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

    2012-02-01

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

  17. An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics

    PubMed Central

    Sheldon, Claire A.; Kwon, Young Joon; Liu, Grant T.; McCormack, Shana E.

    2015-01-01

    Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues. PMID:25420176

  18. Cerebrospinal Fluid Calbindin D Concentration as a Biomarker of Cerebellar Disease Progression in Niemann-Pick Type C1 Disease

    PubMed Central

    Bagel, Jessica; Sampson, Maureen; Farhat, Nicole; Ding, Wenge; Swain, Gary; Prociuk, Maria; O’Donnell, Patricia; Drobatz, Kenneth; Gurda, Brittney; Wassif, Christopher; Remaley, Alan; Porter, Forbes; Vite, Charles

    2016-01-01

    Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear evidence of the therapeutic efficacy of 2-hydroxypropyl-β-cyclodextrin (HPβCD) in animal models resulted in the initiation of a phase I/IIa clinical trial in 2013 and a phase IIb/III trial in 2015. With clinical trials ongoing, validation of a biomarker to track disease progression and serve as a supporting outcome measure of therapeutic efficacy has become compulsory. In this study, we evaluated calcium-binding protein calbindin D-28K (calbindin) concentrations in the cerebrospinal fluid (CSF) as a biomarker of NPC1 disease. In the naturally occurring feline model, CSF calbindin was significantly elevated at 3 weeks of age, prior to the onset of cerebellar dysfunction, and steadily increased to >10-fold over normal at end-stage disease. Biweekly intrathecal administration of HPβCD initiated prior to the onset of neurologic dysfunction completely normalized CSF calbindin in NPC1 cats at all time points analyzed when followed up to 78 weeks of age. Initiation of HPβCD after the onset of clinical signs (16 weeks of age) resulted in a delayed reduction of calbindin levels in the CSF. Evaluation of CSF from patients with NPC1 revealed that calbindin concentrations were significantly elevated compared with CSF samples collected from unaffected patients. Off-label treatment of patients with NPC1 with miglustat, an inhibitor of glycosphingolipid biosynthesis, significantly decreased CSF calbindin compared with pretreatment concentrations. These data suggest that the CSF calbindin concentration is a sensitive biomarker of NPC1 disease that could be instrumental as an outcome measure of therapeutic efficacy in ongoing clinical trials. PMID:27307499

  19. 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

  20. Cerebrospinal Fluid Calbindin D Concentration as a Biomarker of Cerebellar Disease Progression in Niemann-Pick Type C1 Disease.

    PubMed

    Bradbury, Allison; Bagel, Jessica; Sampson, Maureen; Farhat, Nicole; Ding, Wenge; Swain, Gary; Prociuk, Maria; O'Donnell, Patricia; Drobatz, Kenneth; Gurda, Brittney; Wassif, Christopher; Remaley, Alan; Porter, Forbes; Vite, Charles

    2016-08-01

    Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear evidence of the therapeutic efficacy of 2-hydroxypropyl-β-cyclodextrin (HPβCD) in animal models resulted in the initiation of a phase I/IIa clinical trial in 2013 and a phase IIb/III trial in 2015. With clinical trials ongoing, validation of a biomarker to track disease progression and serve as a supporting outcome measure of therapeutic efficacy has become compulsory. In this study, we evaluated calcium-binding protein calbindin D-28K (calbindin) concentrations in the cerebrospinal fluid (CSF) as a biomarker of NPC1 disease. In the naturally occurring feline model, CSF calbindin was significantly elevated at 3 weeks of age, prior to the onset of cerebellar dysfunction, and steadily increased to >10-fold over normal at end-stage disease. Biweekly intrathecal administration of HPβCD initiated prior to the onset of neurologic dysfunction completely normalized CSF calbindin in NPC1 cats at all time points analyzed when followed up to 78 weeks of age. Initiation of HPβCD after the onset of clinical signs (16 weeks of age) resulted in a delayed reduction of calbindin levels in the CSF. Evaluation of CSF from patients with NPC1 revealed that calbindin concentrations were significantly elevated compared with CSF samples collected from unaffected patients. Off-label treatment of patients with NPC1 with miglustat, an inhibitor of glycosphingolipid biosynthesis, significantly decreased CSF calbindin compared with pretreatment concentrations. These data suggest that the CSF calbindin concentration is a sensitive biomarker of NPC1 disease that could be instrumental as an outcome measure of therapeutic efficacy in ongoing clinical trials. PMID:27307499

  1. Simple and validated UHPLC-MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage.

    PubMed

    Mohamed, Susan; Riva, Roberto; Contin, Manuela

    2016-08-15

    We present a simple, fast and validated method for the determination of nimodipine in plasma and cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Plasma or CSF 250μL aliquots were pretreated with acetonitrile spiked with lacosamide as internal standard. The chromatographic separation was performed on a Fusion (3μm) 50×2.0mm I.D. column with gradient elution of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile at a flow rate of 0.35mL/min. The MS/MS ion transitions were 419.1→343 for nimodipine and 251.1→91 for the internal standard. The linearity was determined from 2.0 to 40.0ng/mL in plasma and 40.0-800.0pg/mL in CSF. The lower limit of quantitation (LLOQ) of nimodipine was 0.4ng/mL in plasma and 40pg/mL in CSF. The mean recovery for nimodipine was ≥75% in plasma and ≥90% in CSF at all three considered concentrations. Intra- and interassay precision and accuracy were ≤15% at all quality control concentrations in plasma and CSF. The method was applied to measure plasma and CSF concentrations of nimodipine in a series of patients with subarachnoid haemorrhage treated with intravenous nimodipine. The present procedure, omitting time-consuming liquid-liquid extraction and drying steps, is faster, simpler and cheaper than published LC-MS/MS analytical methods for nimodipine in plasma and the first validated one for nimodipine in CSF. PMID:27327399

  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. Immune Activation and HIV-Specific CD8(+) T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers.

    PubMed

    Ganesh, Anupama; Lemongello, Donna; Lee, Evelyn; Peterson, Julia; McLaughlin, Bridget E; Ferre, April L; Gillespie, Geraldine M; Fuchs, Dietmar; Deeks, Steven G; Hunt, Peter W; Price, Richard W; Spudich, Serena S; Shacklett, Barbara L

    2016-08-01

    The central nervous system (CNS) is an important target of HIV, and cerebrospinal fluid (CSF) can provide a window into host-virus interactions within the CNS. The goal of this study was to determine whether HIV-specific CD8(+) T cells are present in CSF of HIV controllers (HC), who maintain low to undetectable plasma viremia without antiretroviral therapy (ART). CSF and blood were sampled from 11 HC, defined based on plasma viral load (VL) consistently below 2,000 copies/ml without ART. These included nine elite controllers (EC, plasma VL <40 copies/ml) and two viremic controllers (VC, VL 40-2,000 copies/ml). All controllers had CSF VL <40 copies/ml. Three comparison groups were also sampled: six HIV noncontrollers (NC, VL >10,000 copies/ml, no ART); seven individuals with viremia suppressed due to ART (Tx, VL <40 copies/ml); and nine HIV-negative controls. CD4(+) and CD8(+) T cells in CSF and blood were analyzed by flow cytometry to assess expression of CCR5, activation markers CD38 and HLA-DR, and memory/effector markers CD45RA and CCR7. HIV-specific CD8(+) T cells were quantified by major histocompatibility complex class I multimer staining. HIV-specific CD8(+) T cells were detected ex vivo at similar frequencies in CSF of HC and noncontrollers; the highest frequencies were in individuals with CD4 counts below 500 cells/μl. The majority of HIV-specific CD8(+) T cells in CSF were effector memory cells expressing CCR5. Detection of these cells in CSF suggests active surveillance of the CNS compartment by HIV-specific T cells, including in individuals with long-term control of HIV infection in the absence of therapy. PMID:27019338

  4. The Impact of Spinal Cord Nerve Roots and Denticulate Ligaments on Cerebrospinal Fluid Dynamics in the Cervical Spine

    PubMed Central

    Heidari Pahlavian, Soroush; Yiallourou, Theresia; Tubbs, R. Shane; Bunck, Alexander C.; Loth, Francis; Goodin, Mark; Raisee, Mehrdad; Martin, Bryn A.

    2014-01-01

    Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (∼6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS. PMID:24710111

  5. Hydrodynamic and Longitudinal Impedance Analysis of Cerebrospinal Fluid Dynamics at the Craniovertebral Junction in Type I Chiari Malformation

    PubMed Central

    Martin, Bryn A.; Kalata, Wojciech; Shaffer, Nicholas; Fischer, Paul; Luciano, Mark; Loth, Francis

    2013-01-01

    Elevated or reduced velocity of cerebrospinal fluid (CSF) at the craniovertebral junction (CVJ) has been associated with type I Chiari malformation (CMI). Thus, quantification of hydrodynamic parameters that describe the CSF dynamics could help assess disease severity and surgical outcome. In this study, we describe the methodology to quantify CSF hydrodynamic parameters near the CVJ and upper cervical spine utilizing subject-specific computational fluid dynamics (CFD) simulations based on in vivo MRI measurements of flow and geometry. Hydrodynamic parameters were computed for a healthy subject and two CMI patients both pre- and post-decompression surgery to determine the differences between cases. For the first time, we present the methods to quantify longitudinal impedance (LI) to CSF motion, a subject-specific hydrodynamic parameter that may have value to help quantify the CSF flow blockage severity in CMI. In addition, the following hydrodynamic parameters were quantified for each case: maximum velocity in systole and diastole, Reynolds and Womersley number, and peak pressure drop during the CSF cardiac flow cycle. The following geometric parameters were quantified: cross-sectional area and hydraulic diameter of the spinal subarachnoid space (SAS). The mean values of the geometric parameters increased post-surgically for the CMI models, but remained smaller than the healthy volunteer. All hydrodynamic parameters, except pressure drop, decreased post-surgically for the CMI patients, but remained greater than in the healthy case. Peak pressure drop alterations were mixed. To our knowledge this study represents the first subject-specific CFD simulation of CMI decompression surgery and quantification of LI in the CSF space. Further study in a larger patient and control group is needed to determine if the presented geometric and/or hydrodynamic parameters are helpful for surgical planning. PMID:24130704

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

    PubMed

    Chamberlain, M C

    1994-04-01

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

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

    PubMed Central

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

    2016-01-01

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