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Sample records for cerebrospinal fluid samples

  1. Cerebrospinal fluid.

    PubMed

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

    2001-08-01

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

  2. 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

  3. 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

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

    PubMed Central

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

    2015-01-01

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

  5. 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

  6. 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

  7. [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

  8. Higher recovery rate of microorganisms from cerebrospinal fluid samples by the BACTEC culture system in comparison with agar culture.

    PubMed

    Calderaro, Adriana; Martinelli, Monica; Montecchini, Sara; Motta, Federica; Covan, Silvia; Larini, Sandra; Medici, Maria Cristina; Arcangeletti, Maria Cristina; Chezzi, Carlo; De Conto, Flora

    2016-04-01

    The aim of this study was to assess the diagnostic value of the BACTEC FX blood culture (BC) system as compared to the agar culture (AC) of cerebrospinal fluid samples (CSF), evaluating the recovery rate and the time to detection of microorganisms in a 3.5-year period. From December 2011 to May 2015, 1326 CSF samples (694 patients) were submitted to both AC and BC. Among the 150 positive samples (96 patients), 165 microorganisms were detected: 81 by both the protocols, 77 by BC alone, and 7 by AC alone, demonstrating a higher detection rate of BC (95.8%) than AC (53.3%). Although BC presents some disadvantages, it is able to improve the yield of clinically significant microorganisms, and it could potentially reduce the reporting time as compared to AC. The results obtained highlighted the necessity of a combined approach for the successful detection of central nervous system microbial infections. PMID:26867963

  9. 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 ...

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. [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

  17. 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

  18. 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

  19. 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

  20. Comparative Study of Paired Serum and Cerebrospinal Fluid Samples from Neurocysticercosis Patients for the Detection of Specific Antibody to Taenia solium Immunodiagnostic Antigen.

    PubMed

    Sako, Yasuhito; Takayanagui, Osvaldo M; Odashima, Newton S; Ito, Akira

    2015-09-01

    Neurocysticercosis (NCC) is an important disease of the central nervous system caused by infection with Taenia solium metacestodes. In addition to the clinical findings and the imaging analysis, the results of immunological tests are informative for the diagnosis of NCC. To compare the usefulness of serum and cerebrospinal fluid (CSF) samples for antibody detection, paired serum and CSF samples from patients with NCC and other neurological diseases were examined by an enzyme-linked immunosorbent assay with low-molecular-weight antigens purified from T. solium cyst fluid in a blinded fashion. The sensitivity of both serum and CSF samples was 25.0% in inactive NCC cases (n = 4) and 90.9% in active NCC cases (n = 33), and the specificity of serum and CSF was 100% and 95.8%, respectively. When the serum and CSF samples were combined, the sensitivity in active NCC cases became 100%. There was no difference in test performance between serum and CSF samples. Based on these results, we recommend the detection of specific antibodies in serum for the diagnosis of active NCC because of the ease of collection. When the antibody test is negative, however, CSF should be used to confirm NCC and to rule out other medical disorders of the central nervous system. Antibody detection test using only serum or CSF has a limited diagnostic value and cannot be recommended for the diagnosis of suspected inactive NCC cases. PMID:26543392

  1. Comparative Study of Paired Serum and Cerebrospinal Fluid Samples from Neurocysticercosis Patients for the Detection of Specific Antibody to Taenia solium Immunodiagnostic Antigen

    PubMed Central

    Sako, Yasuhito; Takayanagui, Osvaldo M; Odashima, Newton S; Ito, Akira

    2015-01-01

    Neurocysticercosis (NCC) is an important disease of the central nervous system caused by infection with Taenia solium metacestodes. In addition to the clinical findings and the imaging analysis, the results of immunological tests are informative for the diagnosis of NCC. To compare the usefulness of serum and cerebrospinal fluid (CSF) samples for antibody detection, paired serum and CSF samples from patients with NCC and other neurological diseases were examined by an enzyme-linked immunosorbent assay with low-molecular-weight antigens purified from T. solium cyst fluid in a blinded fashion. The sensitivity of both serum and CSF samples was 25.0% in inactive NCC cases (n = 4) and 90.9% in active NCC cases (n = 33), and the specificity of serum and CSF was 100% and 95.8%, respectively. When the serum and CSF samples were combined, the sensitivity in active NCC cases became 100%. There was no difference in test performance between serum and CSF samples. Based on these results, we recommend the detection of specific antibodies in serum for the diagnosis of active NCC because of the ease of collection. When the antibody test is negative, however, CSF should be used to confirm NCC and to rule out other medical disorders of the central nervous system. Antibody detection test using only serum or CSF has a limited diagnostic value and cannot be recommended for the diagnosis of suspected inactive NCC cases. PMID:26543392

  2. 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

  3. [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

  4. Simultaneous profiling of multiple neurochemical pathways from a single cerebrospinal fluid sample using GC/MS/MS with electron capture detection.

    PubMed

    Eckstein, James A; Ammerman, Gina M; Reveles, Jessica M; Ackermann, Bradley L

    2008-06-01

    Biogenic amines and amino acids are widely characterized in the pathways representing neurotransmission. Although several analytical methodologies have been used to detect specific target molecules in relevant fluids such as cerebrospinal fluid (CSF), multiple assays must be used to survey the primary pathways involved. This article describes the development of a GC/MS/MS method capable of analyzing up to 43 analytes (representing 20 amino acids and more than seven neurochemical pathways) from a single 50 microl CSF sample. In this procedure, a CSF sample is first treated with acetonitrile to precipitate proteins. The dried sample is then derivatized with a mixture of 2,2,3,3,3-pentafluoro-1-propanol and pentafluoropropionic acetic anhydride to replace all active hydrogen atoms with fluorine-containing groups. Due to the concentration difference between amino acids and neurotransmitters, these two compound classes are analyzed in separate injections of the same derivatized extract. The total run time for each injection is approximately 15-20 min. An essential feature of the method is the use of argon as a reagent gas for electron capture chemical ionization (ECCI), as the use of the more traditional gas (methane) lacked sufficient durability to be considered for use with the present instrumentation. This article describes the development of this method including a detailed investigation of the chemical ionization conditions used. The resultant conditions allow for the profiling of biogenic amines (e.g. serotonin, norepinephrine, and dopamine) in the low picogram per milliliter range. PMID:18286669

  5. Identification of Common Bacterial Pathogens Causing Meningitis in Culture-Negative Cerebrospinal Fluid Samples Using Real-Time Polymerase Chain Reaction

    PubMed Central

    2016-01-01

    Background. Meningitis is a serious communicable disease with high morbidity and mortality rates. It is an endemic disease in Egypt caused mainly by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. In some settings, bacterial meningitis is documented depending mainly on positive cerebrospinal fluid (CSF) culture results or CSF positive latex agglutination test, missing the important role of prior antimicrobial intake which can yield negative culture and latex agglutination test results. This study aimed to utilize molecular technology in order to diagnose bacterial meningitis in culture-negative CSF samples. Materials and Methods. Forty culture-negative CSF samples from suspected cases of bacterial meningitis were examined by real-time polymerase chain reaction (real-time PCR) for the presence of lytA, bexA, and ctrA genes specific for Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, respectively. Results. Positive real-time PCR results for Streptococcus pneumoniae were detected in 36 (90%) of culture-negative CSF samples while no positive results for Haemophilus influenzae or Neisseria meningitidis were detected. Four (10%) samples were negative by real-time PCR for all tested organisms. Conclusion. The use of molecular techniques as real-time PCR can provide a valuable addition to the proportion of diagnosed cases of bacterial meningitis especially in settings with high rates of culture-negative results. PMID:27563310

  6. Identification of Common Bacterial Pathogens Causing Meningitis in Culture-Negative Cerebrospinal Fluid Samples Using Real-Time Polymerase Chain Reaction.

    PubMed

    Khater, Walaa Shawky; Elabd, Safia Hamed

    2016-01-01

    Background. Meningitis is a serious communicable disease with high morbidity and mortality rates. It is an endemic disease in Egypt caused mainly by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. In some settings, bacterial meningitis is documented depending mainly on positive cerebrospinal fluid (CSF) culture results or CSF positive latex agglutination test, missing the important role of prior antimicrobial intake which can yield negative culture and latex agglutination test results. This study aimed to utilize molecular technology in order to diagnose bacterial meningitis in culture-negative CSF samples. Materials and Methods. Forty culture-negative CSF samples from suspected cases of bacterial meningitis were examined by real-time polymerase chain reaction (real-time PCR) for the presence of lytA, bexA, and ctrA genes specific for Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, respectively. Results. Positive real-time PCR results for Streptococcus pneumoniae were detected in 36 (90%) of culture-negative CSF samples while no positive results for Haemophilus influenzae or Neisseria meningitidis were detected. Four (10%) samples were negative by real-time PCR for all tested organisms. Conclusion. The use of molecular techniques as real-time PCR can provide a valuable addition to the proportion of diagnosed cases of bacterial meningitis especially in settings with high rates of culture-negative results. PMID:27563310

  7. Quantitative Detection of Epstein-Barr Virus DNA in Cerebrospinal Fluid and Blood Samples of Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Musumeci, Rosario; Oggioni, Davide; Andreoni, Simona; Gardinetti, Margherita; Fusco, Letizia; Frigo, Maura; Banfi, Paola; Rottoli, Maria R.; Confalonieri, Paolo; Rezzonico, Monica; Ferrò, Maria T.; Cavaletti, Guido; Frigeni, Barbara; Mascoli, Nerina; Conti, Marta; Antozzi, Carlo; Andreetta, Francesca; Ambrosoni, Elena; Mainardi, Elsa

    2014-01-01

    The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC) positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity. PMID:24722060

  8. 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

  9. 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%.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Diagnostic Accuracy of Presepsin (sCD14-ST) for Prediction of Bacterial Infection in Cerebrospinal Fluid Samples from Children with Suspected Bacterial Meningitis or Ventriculitis

    PubMed Central

    Stubljar, David; Kopitar, Andreja Natasa; Groselj-Grenc, Mojca; Suhadolc, Kristina; Fabjan, Teja

    2015-01-01

    Children with temporary external ventricular drains (EVD) are prone to nosocomial infections. Diagnosis of bacterial meningitis and ventriculitis in these children is challenging due to frequent blood contamination of cerebrospinal fluid (CSF) and the presence of chemical ventriculitis. The aim of this study was to compare diagnostic accuracy of presepsin (sCD14-ST), a novel biomarker of bacterial infection in CSF, to predict bacterial infection in comparison to the accuracy of established biomarkers like those demonstrated in biochemical analysis of CSF. We conducted a prospective study with 18 children with suspected bacterial meningitis or ventriculitis who had 66 episodes of disease. CSF samples were taken from external ventricular drainage. We measured presepsin in CSF, as well as CSF leukocyte count, glucose, and proteins. CSF was also taken to prove bacterial infection with culture methods or with 16S rRNA gene broad-range PCR (SepsiTest; Molzym, Germany). Infection was clinically confirmed in 57 (86%) episodes of suspected meningitis or ventriculitis. Chemical ventriculitis was diagnosed in 9 (14%) episodes of suspected meningitis or ventriculitis. Diagnostic accuracies presented as area under the curve (AUC) for sCD14-ST, leukocytes, and proteins measured in CSF were 0.877 (95% confidence interval [CI], 0.793 to 0.961), 0.798 (95% CI, 0.677 to 0.920), and 0.857 (95% CI, 0.749 to 0.964), respectively. With CSF culture, we detected bacteria in 17 samples, compared to 37 detected with broad-range PCR. It was found that presepsin was present at a significantly higher level in children with clinically proven ventriculitis than in those without meningitis or ventriculitis. Diagnostic accuracies of presepsin were superior to those of leukocytes or proteins in CSF. Presepsin-guided 16S rRNA gene PCR could be used in everyday clinical practice to improve etiological diagnosis of meningitis and ventriculitis and to prescribe more appropriate antibiotics. PMID

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning

    PubMed Central

    SCHIER, J. G.; HUNT, D. R.; PERALA, A.; MCMARTIN, K. E.; BARTELS, M. J.; LEWIS, L. S.; MCGEEHIN, M. A.; FLANDERS, W. D.

    2015-01-01

    Context Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. Objective To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. Methods In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. Results The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6 – 75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14 – 118.4) and only five (23%) controls (median,

  9. [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

  10. 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

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

    PubMed

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

    2015-11-01

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

  12. 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

  13. Cerebrospinal fluid proteome of patients with acute Lyme disease

    PubMed Central

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

    2012-01-01

    During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS) leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early-disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma. PMID:22900834

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

    PubMed Central

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

    1986-01-01

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

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

    PubMed Central

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

    1998-01-01

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

  16. 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)

  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. 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

  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. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Fluid sampling tool

    DOEpatents

    Garcia, Anthony R.; Johnston, Roger G.; Martinez, Ronald K.

    2000-01-01

    A fluid-sampling tool for obtaining a fluid sample from a container. When used in combination with a rotatable drill, the tool bores a hole into a container wall, withdraws a fluid sample from the container, and seals the borehole. The tool collects fluid sample without exposing the operator or the environment to the fluid or to wall shavings from the container.

  13. 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

  14. 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

  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. 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

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

    PubMed

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

    2004-09-01

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

  18. 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

  19. 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

  20. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    SciTech Connect

    Engbaek, F.; Voldby, B

    1982-04-01

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

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

    PubMed

    Cherebillo, Vyacheslav Yu; Elizarov, Andrei Yu; Polegaev, Andrei V

    2015-09-01

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

  4. Fluid sampling device

    NASA Technical Reports Server (NTRS)

    Studenick, D. K. (Inventor)

    1977-01-01

    An inlet leak is described for sampling gases, more specifically, for selectively sampling multiple fluids. This fluid sampling device includes a support frame. A plurality of fluid inlet devices extend through the support frame and each of the fluid inlet devices include a longitudinal aperture. An opening device that is responsive to a control signal selectively opens the aperture to allow fluid passage. A closing device that is responsive to another control signal selectively closes the aperture for terminating further fluid flow.

  5. 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

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

    PubMed Central

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

    2015-01-01

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

  7. EDA-containing fibronectin levels in the cerebrospinal fluid of children with meningitis.

    PubMed

    Pupek, Małgorzata; Jasonek, Jolanta; Kątnik-Prastowska, Iwona

    2013-01-01

    Fibronectin containing an alternatively spliced extra domain A (EDA-FN) participates in diverse biological cell functions, being also directly or indirectly engaged during an inflammatory response to brain injury and/or neuron regeneration. We analyzed FN and EDA-FN isoform levels by ELISA in 85 cerebrospinal fluid samples and 67 plasma samples obtained from children suffering from bacterial or viral meningitis and non-meningitis peripheral inflammation. We have found that the cerebrospinal level of EDA-FN was significantly lower in the bacterial meningitis group than in the viral- and non-meningitis groups. In the patients' plasma, EDA-FN was almost undetectable. The determination of fibronectin containing the EDA segment might be considered as an additional diagnostic marker of bacterial meningitis in children. PMID:23884219

  8. 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

  9. 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

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

    PubMed

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

    1993-06-01

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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2009-11-01

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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents

    PubMed Central

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

    2016-01-01

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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

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

    PubMed

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

    2014-08-28

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1982-05-01

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

  17. 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

  18. 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

  19. 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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    1996-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

  4. Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer's disease.

    PubMed

    Alcolea, Daniel; Vilaplana, Eduard; Pegueroles, Jordi; Montal, Victor; Sánchez-Juan, Pascual; González-Suárez, Andrea; Pozueta, Ana; Rodríguez-Rodríguez, Eloy; Bartrés-Faz, David; Vidal-Piñeiro, Dídac; González-Ortiz, Sofía; Medrano, Santiago; Carmona-Iragui, María; Sánchez-Saudinós, MaBelén; Sala, Isabel; Anton-Aguirre, Sofía; Sampedro, Frederic; Morenas-Rodríguez, Estrella; Clarimón, Jordi; Blesa, Rafael; Lleó, Alberto; Fortea, Juan

    2015-06-01

    Cerebrospinal fluid YKL-40 has been described as a marker of glial inflammation. We aimed to study the relationship between YKL-40 and brain structure and its interactions with core Alzheimer's disease (AD) biomarkers. We measured cortical thickness (CTh) and cerebrospinal fluid biomarkers (amyloid-β 1-42 [Aβ42], total tau, p-tau, and YKL-40) of 80 cognitively normal controls and 27 patients with amnestic mild cognitive impairment. Subjects were classified as Aβ42+ (<550 pg/mL) or Aβ42- (>550 pg/mL). CTh difference maps were derived from the interaction and correlation analyses in the whole sample and within clinical groups. There was a strong correlation between YKL-40 and markers of neurodegeneration (total tau and p-tau). In the whole sample, we found a negative correlation between YKL-40 and CTh in AD vulnerable areas in Aβ42+ subjects but not in Aβ42 participants. Our results suggest that YKL-40 could track the inflammatory processes associated to tau-related neurodegeneration in the presence of the AD pathophysiological process. PMID:25865441

  5. 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

  6. Fluid sampling tool

    DOEpatents

    Johnston, Roger G.; Garcia, Anthony R. E.; Martinez, Ronald K.

    2001-09-25

    The invention includes a rotatable tool for collecting fluid through the wall of a container. The tool includes a fluid collection section with a cylindrical shank having an end portion for drilling a hole in the container wall when the tool is rotated, and a threaded portion for tapping the hole in the container wall. A passageway in the shank in communication with at least one radial inlet hole in the drilling end and an opening at the end of the shank is adapted to receive fluid from the container. The tool also includes a cylindrical chamber affixed to the end of the shank opposite to the drilling portion thereof for receiving and storing fluid passing through the passageway. The tool also includes a flexible, deformable gasket that provides a fluid-tight chamber to confine kerf generated during the drilling and tapping of the hole. The invention also includes a fluid extractor section for extracting fluid samples from the fluid collecting section.

  7. [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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  19. 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

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

    SciTech Connect

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

    1982-11-01

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

  1. Wireline fluid sampling

    SciTech Connect

    Michaels, J.; Moody, M.; Shwe, T.

    1995-12-31

    Accurate PVT data are crucial to well completion and production, formation evaluation and reservoir characterization. This is especially true for initial reservoir characterization where the PVF sample needs to be obtained prior to production. It is essential that the fluid sample be recovered as closely as possible to in-situ conditions whether by drill stem or wireline formation for. The need to remove drilling mud filtrate prior to collecting a sample has been widely recognized. Wireline testers which can pump fluid from a formation until filtrate is reduced to a minimum overcome this problem. While reducing sample contamination has been addressed, little emphasis has been placed on the need to control inlet pressure during filtrate removal or during sampling. Reducing contamination is important; however, there is equal need to determine the critical sampling pressure. The purpose is to prevent phase separation in the formation by regulating the sampling process based on this information and thereby obtain a more representative reservoir fluid sample. A recently introduced wireline instrument provides the capability of measuring the critical pressure prior to sampling, of controlling the sample pressure and of increasing the pressure in the sample container to compensate for temperature decline during delivery of that sample to a testing laboratory. Example of pressure tests while pumping and during pressure buildup are presented along with indicated sample properties. Introduction Wireline Formation Testers (WFT) provide an cost effective means to determine pressure as a function of depth and to recover samples of fluid from formations at selected depths. No other method can provide this type of information. Pressure data are used to estimate mobility, fluid contact and fluid density.

  2. 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

  3. 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

  4. 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

  5. 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

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

    PubMed Central

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

    1985-01-01

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

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

    PubMed Central

    Jamal, Hira; Abrams, Gary

    2016-01-01

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

  8. Fluid sampling tool

    DOEpatents

    Garcia, Anthony R.; Johnston, Roger G.; Martinez, Ronald K.

    1999-05-25

    A fluid sampling tool for sampling fluid from a container. The tool has a fluid collecting portion which is drilled into the container wall, thereby affixing it to the wall. The tool may have a fluid extracting section which withdraws fluid collected by the fluid collecting section. The fluid collecting section has a fluted shank with an end configured to drill a hole into a container wall. The shank has a threaded portion for tapping the borehole. The shank is threadably engaged to a cylindrical housing having an inner axial passageway sealed at one end by a septum. A flexible member having a cylindrical portion and a bulbous portion is provided. The housing can be slid into an inner axial passageway in the cylindrical portion and sealed to the flexible member. The bulbous portion has an outer lip defining an opening. The housing is clamped into the chuck of a drill, the lip of the bulbous section is pressed against a container wall until the shank touches the wall, and the user operates the drill. Wall shavings (kerf) are confined in a chamber formed in the bulbous section as it folds when the shank advances inside the container. After sufficient advancement of the shank, an o-ring makes a seal with the container wall.

  9. Fluid sampling tool

    DOEpatents

    Garcia, A.R.; Johnston, R.G.; Martinez, R.K.

    1999-05-25

    A fluid sampling tool is described for sampling fluid from a container. The tool has a fluid collecting portion which is drilled into the container wall, thereby affixing it to the wall. The tool may have a fluid extracting section which withdraws fluid collected by the fluid collecting section. The fluid collecting section has a fluted shank with an end configured to drill a hole into a container wall. The shank has a threaded portion for tapping the borehole. The shank is threadably engaged to a cylindrical housing having an inner axial passageway sealed at one end by a septum. A flexible member having a cylindrical portion and a bulbous portion is provided. The housing can be slid into an inner axial passageway in the cylindrical portion and sealed to the flexible member. The bulbous portion has an outer lip defining an opening. The housing is clamped into the chuck of a drill, the lip of the bulbous section is pressed against a container wall until the shank touches the wall, and the user operates the drill. Wall shavings (kerf) are confined in a chamber formed in the bulbous section as it folds when the shank advances inside the container. After sufficient advancement of the shank, an o-ring makes a seal with the container wall. 6 figs.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Mattsson, Niklas

    2016-01-01

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

  12. 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

  13. 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

  14. 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

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  16. 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

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

    PubMed

    Simpson, S; Yung, M; Slater, A

    2006-10-01

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

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

    PubMed

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

    2016-09-01

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

  19. Analgesic and thermic effects, and cerebrospinal fluid and plasma pharmacokinetics, of intracerebroventricularly administered morphine in normal and sensitized rats.

    PubMed

    Bhargava, H N; Villar, V M; Cortijo, J; Morcillo, E J

    1998-02-01

    The relationship between asthma and opioids has barely been investigated. This study examines whether active sensitization of rats changes the analgesic and thermic effects of intracerebroventricular morphine or the pharmacokinetics of the drug. Morphine (5, 10 and 20 microg) was given intracerebroventricularly to sensitized (active immunization to ovalbumin and Al(OH)3 then airway challenge with ovalbumin after 12 days) and normal (i.e. non-sensitized) male Sprague-Dawley rats. The tail-flick latencies and changes in colon temperature were determined before morphine injection and at 30 min intervals for a period of 300 min afterwards. Results were expressed as the area under the time-response curve. The analgesic and hyperthermic response to morphine for sensitized rats was less than that obtained for normal rats. Cerebrospinal fluid and blood samples were collected periodically for a period of 240 min and morphine levels were determined by a highly sensitive radioimmunoassay. The pharmacokinetic parameters half-life, terminal elimination rate constant and the mean residence time were determined in both cerebrospinal fluid and plasma by non-compartmental analysis. The area under the cerebrospinal fluid concentration-time curve from time zero to infinity was higher for sensitized rats than for normal rats for all three doses of morphine but these differences did not correspond with similar changes in pharmacological responses. In conclusion, the attenuated analgesic and thermic responses to intracerebroventricular morphine in the sensitized rats might be a result of pharmacodynamic alterations rather than to pharmacokinetic changes. PMID:9530988

  20. 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

  1. 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

  2. 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...

  3. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-06-01

    Central catecholamine deficiency characterizes α-synucleinopathies such as Parkinson's disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson's disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinal fluid catechols were assayed in 146 subjects-108 synucleinopathy patients (34 Parkinson's disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinal fluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson's disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinal fluid dihydroxyphenylacetic acid [0.86 ± 0.09 (SEM), 1.00 ± 0.09, 1.32 ± 0.12 nmol/l] than controls (2.15 ± 0.18 nmol/l; P < 0.0001; P < 0.0001; P = 0.0002). Dihydroxyphenylglycol was also lower in the three synucleinopathies (8.82 ± 0.44, 7.75 ± 0.42, 5.82 ± 0.65 nmol/l) than controls (11.0 ± 0.62 nmol/l; P = 0.009, P < 0.0001, P < 0.0001). Dihydroxyphenylacetic acid was lower and dihydroxyphenylglycol higher in Parkinson's disease than in pure autonomic failure. Dihydroxyphenylacetic acid was 100% sensitive at 89% specificity in separating patients with recent onset of parkinsonism from controls but was of no value in differentiating Parkinson's disease from multiple system atrophy. Synucleinopathies feature cerebrospinal fluid neurochemical evidence for central dopamine and norepinephrine deficiency. Parkinson's disease and pure autonomic failure involve differential dopaminergic versus noradrenergic lesions. Cerebrospinal fluid

  6. 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

  7. 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

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

    PubMed Central

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

    2016-01-01

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

  9. 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.

  10. 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

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

    PubMed

    Lenart, Mark J; Carness, Jeffrey M

    2016-09-01

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

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

    PubMed

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

    2005-05-01

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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Scheld, W M; Brodeur, J P

    1983-01-01

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

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

    PubMed

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

    2016-08-01

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

  1. 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

  2. Fluid sampling system

    DOEpatents

    Houck, Edward D.

    1994-01-01

    An fluid sampling system allows sampling of radioactive liquid without spillage. A feed tank is connected to a liquid transfer jet powered by a pumping chamber pressurized by compressed air. The liquid is pumped upwardly into a sampling jet of a venturi design having a lumen with an inlet, an outlet, a constricted middle portion, and a port located above the constricted middle portion. The liquid is passed under pressure through the constricted portion causing its velocity to increase and its pressure to decreased, thereby preventing liquid from escaping. A septum sealing the port can be pierced by a two pointed hollow needle leading into a sample bottle also sealed by a pierceable septum affixed to one end. The bottle is evacuated by flow through the sample jet, cyclic variation in the sampler jet pressure periodically leaves the evacuated bottle with lower pressure than that of the port, thus causing solution to pass into the bottle. The remaining solution in the system is returned to the feed tank via a holding tank.

  3. Fluid sampling system

    DOEpatents

    Houck, E.D.

    1994-10-11

    An fluid sampling system allows sampling of radioactive liquid without spillage. A feed tank is connected to a liquid transfer jet powered by a pumping chamber pressurized by compressed air. The liquid is pumped upwardly into a sampling jet of a venturi design having a lumen with an inlet, an outlet, a constricted middle portion, and a port located above the constricted middle portion. The liquid is passed under pressure through the constricted portion causing its velocity to increase and its pressure to be decreased, thereby preventing liquid from escaping. A septum sealing the port can be pierced by a two pointed hollow needle leading into a sample bottle also sealed by a pierceable septum affixed to one end. The bottle is evacuated by flow through the sample jet, cyclic variation in the sampler jet pressure periodically leaves the evacuated bottle with lower pressure than that of the port, thus causing solution to pass into the bottle. The remaining solution in the system is returned to the feed tank via a holding tank. 4 figs.

  4. Fluid sampling system

    SciTech Connect

    Houck, E.D.

    1993-12-31

    This invention comprises a fluid sampling system which allows sampling of radioactive liquid without spillage. A feed tank is connected to a liquid transfer jet powered by a pumping chamber pressurized by compressed air. The liquid is pumped up into a sampling jet of venturi design having a lumen with an inlet, an outlet, a constricted middle portion, and a port located above the constricted middle portion. The liquid is passed under pressure through the constricted portion causing its velocity to increase and its pressure to decrease, thereby preventing liquid from escaping. A septum sealing the port can be pierced by a two pointed hollow needle leading into a sample bottle also sealed by a pierceable septum affixed to one end. The bottle is evacuated by flow through the sample jet, cyclic variation in the sampler jet pressure periodicially leaves the evacuated bottle with lower pressure than that of the port, thus causing solution to pass into the bottle. The remaining solution in the system is returned to the feed tank via a holding tank.

  5. Lack of usutu virus RNA in cerebrospinal fluid of patients with encephalitis of unknown etiology, Tuscany, Italy.

    PubMed

    Maggi, Fabrizio; Mazzetti, Paola; Focosi, Daniele; Macera, Lisa; Scagnolari, Carolina; Manzin, Aldo; Antonelli, Guido; Nelli, Luca Ceccherini

    2015-06-01

    Usutu virus (USUV) is an African mosquito-borne flavivirus associated with human neurological disorders in Europe. Recently, USUV introduction in Europe has been traced back to Eurasian blackbirds deaths in the Tuscany region of Italy in 1996. Ninety-six cerebrospinal fluid (CSF) samples from patients with encephalitis of unknown etiology diagnosed in 2010-2013 were screened to determine whether USUV circulates in humans in Tuscany. Using real-time polymerase chain reaction, no positive patient was found. USUV does not seem to cause neuroinvasive disorders in humans in Tuscany. PMID:25712912

  6. 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

  7. 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

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

    PubMed Central

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

    2008-01-01

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

  9. 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

  10. 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.

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

    PubMed Central

    Dotevall, L; Hagberg, L

    1989-01-01

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

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

    PubMed

    MOHUN, A F; COOK, I J

    1962-03-01

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

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

    PubMed

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

    2016-02-01

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

  14. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Ikeda, K; Nakano, M; Tani, E

    1978-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

  19. 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

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

    PubMed Central

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

    2009-01-01

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

  1. 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

  2. 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

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

    PubMed Central

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

    2016-01-01

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

  4. 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

  5. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease.

    PubMed

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M; Lewczuk, Piotr; de Leon, Mony J; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  6. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

    PubMed Central

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  7. The UKNEQAS scheme for cerebrospinal fluid haem pigments: a paradigm for service improvement.

    PubMed

    Beetham, Robert; Egner, William; Patel, Dina

    2011-11-01

    We describe the programme of an established External Quality Assurance (EQA) provider and a Specialist Advisory Group (SAG) to develop a successful EQA scheme for cerebrospinal fluid (CSF) haem pigments as an example of a professionally led, unfunded initiative with the real potential to benefit patients. Within three years, we had assured sample stability, stoichiometry, and published best practice guidelines, enabling both analytical results and interpretation to be assessed and reported with an educative summary of the desired responses. Misclassification scoring of analysis and interpretation was introduced. Following audit, guidelines were modified and republished. The outcomes were as follows: Participant numbers increased from 63 at inception to 150 10 years later; The percentage of participants using visual inspection, a poor practice indicator, decreased from 27% to less than 1%; In all, 94-100% of participants consistently detected minor increases in bilirubin over the last four years of the scheme; More than 93% of participants were able to interpret analytical results linked to straightforward clinical scenarios; Misclassification scoring demonstrated that more complex scenarios repeatedly posed problems and is the next challenge to address. Scheme success is attributed to the experience of the operator and the formation of a voluntary expert advisory group, with both concerned to advance science and patient safety and thus contribute unpaid time and effort in order to succeed. In times of fiscal constraint, such resource may not be so readily available, yet is a vital part of continuous quality improvement for the benefit of patients. PMID:21948489

  8. 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

  9. 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

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

    PubMed Central

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

    2013-01-01

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

  11. Detection Of Human Herpesvirus-6 In Cerebrospinal Fluid Of Patients With Encephalitis

    PubMed Central

    Yao, Karen; Honarmand, Somayeh; Espinoza, Alex; Akhyani, Nahid; Glaser, Carol; Jacobson, Steven

    2009-01-01

    Objective Virus infections are the most common causes of encephalitis, a syndrome characterized by acute inflammation of the brain. Over 150 different viruses have been implicated in the pathogenesis of encephalitis, however due to limitations with diagnostic testing, etiologies of over half of the cases remain unknown. Methods To investigate whether HHV-6 is an etiological agent of encephalitis, we examined for evidence of virus infection by determining the presence of viral sequence using PCR and assessed HHV-6 antibody reactivity in the cerebrospinal fluids (CSF) of encephalitis patients with unknown etiology. In a cohort study, we compared virus specific antibody levels in CSF samples of patients with encephalitis, relapsing-remitting MS and other neurologic diseases (OND). Results Our results demonstrated elevated levels of HHV-6 IgG as well as IgM levels in a subset of encephalitis patients compared with OND. Moreover, cell-free viral DNA that is indicative of active infection was detected in 40% (14/35) of encephalitis patients, while no amplifiable viral sequence was found in either relapsing-remitting MS or OND patients. Additionally, a significant correlation between PCR detection and anti-HHV-6 antibody response was also demonstrated. Interpretation Collectively, these results suggested HHV-6 as a possible pathogen in a subset of encephalitis cases. PMID:19334059

  12. 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

  13. 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.

  14. 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

  15. Cerebrospinal Fluid Metabolome in Mood Disorders-Remission State has a Unique Metabolic Profile

    PubMed Central

    Kaddurah-Daouk, Rima; Yuan, Peixiong; Boyle, Stephen H.; Matson, Wayne; Wang, Zhi; Zeng, Zhao Bang; Zhu, Hongjie; Dougherty, George G.; Yao, Jeffrey K.; Chen, Guang; Guitart, Xavier; Carlson, Paul J.; Neumeister, Alexander; Zarate, Carlos; Krishnan, Ranga R.; Manji, Husseini K.; Drevets, Wayne

    2012-01-01

    Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion. PMID:22993692

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed

    Christiansen, Ingelise

    2015-01-01

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

  1. Application of Control Volume Analysis to Cerebrospinal Fluid Dynamics

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

  2. Coupling poroelasticity and CFD for cerebrospinal fluid hydrodynamics.

    PubMed

    Tully, Brett; Ventikos, Yiannis

    2009-06-01

    This research uses a novel coupling of poroelastic theory and computational fluid dynamics to investigate acute hydrocephalus resulting from stenosis of the cerebral aqueduct. By coupling poroelastic theory with a multidimensional simulation of the cerebral aqueduct we are able to investigate, for the first time, the impact of physically relevant stenosis patterns on ventricular enlargement, accounting for the nonintuitive long time history responses of the ventricular system. Preliminary findings demonstrate clearly the importance that the fluidic-poroelastic coupling plays: ventricular enlargement is significantly smaller with local stenosis patterns and almost all of the observable pressure drop occurs across the stenosis. Short timescale effects [O(heartbeat)] are explored and their contribution to the long timescales interrogated. PMID:19304478

  3. 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

  4. 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

  5. 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

  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. 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. 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

  9. High-performance liquid chromatography of amino acids in urine and cerebrospinal fluid.

    PubMed

    Lam, S; Azumaya, H; Karmen, A

    1984-10-19

    Two different methods for analyzing amino acids by reversed-phase high-performance liquid chromatography (HPLC), both of which can separate D- and L- stereoisomers, have been used for studying the amino acid composition of cerebrospinal fluid (CSF) and urine. One method, by which Dns derivatives of amino acids are separated as mixed chelate complexes with Cu(II) and a single stereoisomer of a second amino acid, was used to analyze CSF. CSF contains ca. 10 mumole/l per amino acid, compared to 100 mumole/l in serum. The high sensitivity of fluorescence detection enabled complete analysis, starting with 50 microliter of fluid. The second method, which uses lower concentrations of both the copper and the second amino acid and detects amino acids by the change in absorbance of the copper complex, was used to measure the urine concentration of the lysine metabolite, pipecolic acid (piperidine-2-carboxylic acid), a secondary amino acid that is difficult to detect by the more usual detection methods. Our procedure involves passing urine through a cation-exchange column, collecting the fraction containing pipecolic acid, and chromatographing it on a reversed-phase HPLC column with a mobile phase containing L-aspartame and Cu(II). To assess the utility of the method, urine samples from a patient given loading doses of D- or L-isomers were analyzed. When either isomer was administered, both D- and L-isomers were detected, but in different proportions. Varying proportions and concentrations of both isomers were also detected in the urines of patients with hyperpipecolatemia from different metabolic abnormalities. PMID:6501504

  10. 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

  11. Lack of KIs virus DNA in plasma and cerebrospinal fluid in Italy.

    PubMed

    Macera, Lisa; Focosi, Daniele; Manzin, Aldo; Ceccherini Nelli, Luca; Pistello, Mauro; Maggi, Fabrizio

    2015-10-01

    Dear Sirs, Satoh et al. recently screened 516 Japanese blood donors with PCR using primers constructed from the consensus domain of the helicase of positive-stranded RNA viruses. They reported a novel enveloped virus with a circular double-stranded DNA genome (tentatively named KIs virus, KIs-V) (Satoh et al., 2011) occurring in 36 out of the 100 hepatitis E (HEV) antibody-positive donors with elevated alanine aminotransferase (ALT) levels (>60 IU/L). More recently, Biagini et al. failed to find KIs-V in plasma from 576 French blood donors with unknown HEV serostatus and unknown ALT values (Biagini et al., 2012). Based on an HEV seroprevalence of 3-52% in France, the authors suggested an uncommon frequency of KIs-V infection in healthy persons in France. To date, no information has been available on the prevalence of KIs-V DNA in Italy. In the present paper, we analyzed KIs-V in 242 plasma samples of blood donors, transplant recipients, and patients with chronic viral infections, and in 52 cerebrospinal fluid (CSF) samples of patients with different neurological disorders. Informed consent was obtained from all patients and the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its amendments. Viral DNA extraction was carried out on 200 μl of plasma or 200 μl of CSF by using QIAamp DNA blood kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Extracted nucleic acids were amplified for KIs-V DNA with the nested PCR protocol developed by Satoh et al. (2011) and used for screening Japanese blood donors. The first and second PCR rounds were designed on 458 and 304 nt-length fragments, respectively. To validate the amplification process, positive controls obtained from plasma dilutions of a synthetic template corresponding to the target sequence were run in each PCR. PCR sensitivity was less than 5 copies of target sequence. Fourteen liver and 16 kidney and/or pancreas transplant

  12. [A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

    PubMed

    Arita, Yuki; Tono, Toshihiro; Hosoda, Tomohiro; Taguchi, Hiroaki; Sakamoto, Mitsuo; Osone, Yasuo; Nozaki, Hiroyuki

    2016-05-01

    We report a patient with leptospirosis caused by infection with Leptospira interrogans serovar Rachmati. A 30-year-old Japanese man took part in a survival camp on Iriomote Island, Okinawa, from July 9 to July 15, 2014. During the camp, he swam in the river and kayaked. He developed a high fever and fatigue 7 days after completing his trip and was admitted to our hospital on July 22. On admission, he complained of a posterior cervical pain and a loss of appetite. Laboratory findings revealed granulocytosis, mildly elevated AST and ALT levels, elevated BUN and Cr levels, and a significantly elevated CRP level. No pathogenic bacteria were isolated from blood, urine, or cerebrospinal fluid cultures. We included leptospirosis in the differential diagnosis because of the patient's history of participating in a survival camp on Iriomote Island. Minocycline 200 mg, p.o. showed an excellent efficacy. The Leptospira flagellar gene FlaB was detected using a cerebrospinal fluid PCR. A microscopic agglutination test (MAT) during the convalescent stage demonstrated significant increases in antibodies against L. interrogans serovar Rachmati, confirming the diagnosis of leptospirosis. A medical history including occupation and recent travel history, and an adequate specimen sampling are crucial for the accurate and early diagnosis of leptospirosis. PMID:27529969

  13. 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

  14. 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

  15. 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

  16. 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

  17. Cerebrospinal fluid leakage and headache after lumbar puncture: a prospective non-invasive imaging study.

    PubMed

    Wang, Yen-Feng; Fuh, Jong-Ling; Lirng, Jiing-Feng; Chen, Shih-Pin; Hseu, Shu-Shya; Wu, Jaw-Ching; Wang, Shuu-Jiun

    2015-06-01

    The spatial distribution and clinical correlation of cerebrospinal fluid leakage after lumbar puncture have not been determined. Adult in-patients receiving diagnostic lumbar punctures were recruited prospectively. Whole-spine heavily T2-weighted magnetic resonance myelography was carried out to characterize post-lumbar puncture spinal cerebrospinal fluid leakages. Maximum rostral migration was defined as the distance between the most rostral spinal segment with cerebrospinal fluid leakage and the level of lumbar puncture. Eighty patients (51 female/29 male, mean age 49.4 ± 13.3 years) completed the study, including 23 (28.8%) with post-dural puncture headache. Overall, 63.6% of periradicular leaks and 46.9% of epidural collections were within three vertebral segments of the level of lumbar puncture (T12-S1). Post-dural puncture headache was associated with more extensive and more rostral distributions of periradicular leaks (length 3.0 ± 2.5 versus 0.9 ± 1.9 segments, P = 0.001; maximum rostral migration 4.3 ± 4.7 versus 0.8 ± 1.7 segments, P = 0.002) and epidural collections (length 5.3 ± 6.1 versus 1.0 ± 2.1 segments, P = 0.003; maximum rostral migration 4.7 ± 6.7 versus 0.9 ± 2.4 segments, P = 0.015). In conclusion, post-dural puncture headache was associated with more extensive and more rostral distributions of periradicular leaks and epidural collections. Further, visualization of periradicular leaks was not restricted to the level of dural defect, although two-thirds remained within the neighbouring segments. PMID:25688077

  18. Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla.

    PubMed

    Stocker, Sean D; Lang, Susan M; Simmonds, Sarah S; Wenner, Megan M; Farquhar, William B

    2015-12-01

    Elevated NaCl concentrations of the cerebrospinal fluid increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or polysynaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to cerebrospinal fluid hypernatremia. Lateral ventricle infusion of 0.15 mol/L, 0.6 mol/L, and 1.0 mol/L NaCl (5 µL/10 minutes) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure, despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the gamma-aminobutyric acid (GABAA) agonist muscimol abolished the sympathoexcitatory response to intracerebroventricular infusion of 1 mol/L NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and arterial blood pressure. Finally, single-unit recordings of spinally projecting RVLM neurons revealed 3 distinct populations based on discharge responses to intracerebroventricular infusion of 1 mol/L NaCl: type I excited (46%; 11/24), type II inhibited (37%; 9/24), and type III no change (17%; 4/24). All neurons with slow conduction velocities were type I cells. Collectively, these findings suggest that acute increases in cerebrospinal fluid NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and arterial blood pressure. PMID:26416846

  19. 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

  20. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-03-15

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

  4. 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

  5. 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.

  6. 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

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

    PubMed

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

    2016-06-01

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

  8. 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

  9. Cucurbitacin I blocks cerebrospinal fluid and platelet derived growth factor-BB stimulation of leptomeningeal and meningioma DNA synthesis

    PubMed Central

    2013-01-01

    Background Currently, there are no consistently effective chemotherapies for recurrent and inoperable meningiomas. Recently, cucurbitacin I (JSI-124), a naturally occurring tetracyclic triterpenoid compound used as folk medicines has been found to have cytoxic and anti-proliferative properties in several malignancies thru inhibition of activator of transcription (STAT3) activation. Previously, we have found STAT3 to be activated in meningiomas, particularly higher grade tumors. Methods Primary leptomeningeal cultures were established from 17, 20 and 22 week human fetuses and meningioma cell cultures were established from 6 World Health Organization (WHO) grade I or II meningiomas. Cells were treated with cerebrospinal fluid from patients without neurologic disease. The effects of cucurbitacin I on cerebrospinal fluid stimulation of meningioma cell DNA synthesis phosphorylation/activation of JAK1, STAT3, pMEK1/2, p44/42MAPK, Akt, mTOR, Rb and caspase 3 activation were analyzed in human leptomeningeal and meningioma cells. Results Cerebrospinal fluid significantly stimulated DNA synthesis in leptomeningeal cells. Co-administration of cucurbitacin I (250 nM) produces a significant blockade of this effect. Cucurbitacin I alone also produced a significant reduction in basal DNA synthesis. In grade I and II meningiomas, cerebrospinal fluid also significantly stimulated DNA synthesis. Co-administration of cucurbitacin I (250 nM) blocked this effect. In the leptomeningeal cultures, cerebrospinal fluid stimulated STAT3 phosphorylation but not p44/42MAPK, Akt or mTOR. Cucurbitacin I had no effect on basal STAT3 phosphorylation but co-administration with cerebrospinal fluid blocked cerebrospinal fluid stimulation of STAT3 phosphorylation in each. In the grade I meningiomas, cerebrospinal fluid stimulated phosphorylation of STAT3 and decreased MEK1/2 and cucurbitacin I had no effect on basal STAT3, p44/42MAPK, Akt, JAK1, mTOR, or Rb phosphorylation. In the grade II

  10. 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