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Sample records for hypotension cerebrospinal fluid

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

    PubMed

    Christiansen, Ingelise

    2015-01-05

    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.

  2. Effects of hypercapnia and arterial hypotension and hypertension on cerebrospinal fluid pulse pressure and intracranial volume-pressure relationships.

    PubMed Central

    Avezaat, C J; van Eijndhoven, J H; Wyper, D J

    1980-01-01

    In twelve anaesthetised, ventilated dogs the effects of hypercapnia and pharmacologically induced arterial hypotension and hypertension on the interrelation between volume-pressure response (VPR) and cerebro-spinal fluid (CSF) pulse pressure were studied during continuous inflation of a supratentorial extradural balloon. Hypercapnia did not significantly affect the intracranial volume-pressure relationships, but did cause a significant increase in gradient of the relationship between CSF pulse pressure and intracranial pressure (ICP). Alteration of the arterial blood pressure showed opposite effects on VPR and CSF pulse pressure. A decrease in VPR and an increase in pulse pressure were observed during arterial hypotension; the reverse was found during arterial hypertension. The discrepancy between the effects on VPR and CSF pulse pressure of the variables under study was explained by changes in the transient increase in cerebral blood volume per cardiac cycle. On the basis of the results of this study it will be possible, during clinical ICP monitoring, to interpret changes in the CSF pulse pressure to ICP ratio in terms of changes in intracranial volume-pressure relationships. PMID:7373319

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

    PubMed Central

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

    2012-01-01

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

  4. Cerebral vasospasm following intracranial hypotension caused by cerebrospinal fluid leak from an incidental lumbar durotomy. Case report.

    PubMed

    Chaves, Claudia; Freidberg, Stephen R; Lee, Grace; Zerris, Vasilios; Ries, Sarah; Chavali, Ram

    2005-01-01

    The authors report on the unusual case of a patient with intracranial hypotension following an incidental durotomy complicated by an extensive but reversible cerebral vasospasm. Despite the dural tear repair and correction of the intracranial hypotension, the vasospasm ran its course. The precise mechanism of the cerebral vasospasm in this patient is unclear.

  5. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension.

    PubMed

    Ohwaki, Kazuhiro; Yano, Eiji; Shinohara, Takayuki; Watanabe, Takehiro; Ogawa, Akiko; Fujii, Norio; Nakagomi, Tadayoshi

    2014-09-01

    Although many studies have described various features of neuroimaging tests associated with intracranial hypotension, few have examined their validity and reliability. We evaluated the association between CSF leaks detected by radionuclide cisternography and abnormal MRI findings in the accurate diagnosis of intracranial hypotension. We retrospectively assessed 250 patients who were suspected of intracranial hypotension and underwent subsequent radionuclide cisternography. We obtained 159 sagittal and 153 coronal T2-weighted MRI images and 101 gadolinium-enhanced T1-weighted MRI images. We assessed the CSF leaks in relation to a sagging brain, the maximum subdural space in sagittal and coronal images, and dural enhancement. Overall, 186 (74%) patients showed CSF leaks on radionuclide cisternography. A sagging brain was observed in 21 (13%) of the 159 patients with sagittal MRIs. A sagging brain was not associated with CSF leaks (14% vs. 10%; p=0.49). Compared to patients without CSF leaks, those with CSF leaks tended to have a larger maximum subdural space in both the sagittal (3.7 vs. 4.1mm) and coronal (2.5 vs. 2.8mm) images; however, the differences were not significant (p=0.18 and p=0.53, respectively). Dural enhancement was observed only in one patient, who presented with CSF leaks on radionuclide cisternography. Our study, which included a relatively large population, did not find any association between the findings of radionuclide cisternography and MRI. Future research should focus on identifying more valid neuroimaging findings to diagnose intracranial hypotension accurately. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

    PubMed

    Kaiserova, Michaela; Prikrylova Vranova, Hana; Galuszka, Jan; Stejskal, David; Mensikova, Katerina; Zapletalova, Jana; Mares, Jan; Kanovsky, Petr

    2015-10-01

    An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD.

  7. Epidural Blood Patch Performed for Severe Intracranial Hypotension Following Lumbar Cerebrospinal Fluid Drainage for Intracranial Aneurysm Surgery. Retrospective Series and Literature Review

    PubMed Central

    Tanweer, Omar; Kalhorn, Stephen P.; Snell, Jamaal T.; Lieber, Bryan A.; Agarwal, Nitin; Huang, Paul P.; Sutin, Kenneth M.

    2015-01-01

    Intracranial hypotension (IH) can occur following lumbar drainage for clipping of an intracranial aneurysm. We observed 3 cases of IH, which were all successfully treated by epidural blood patch (EBP). Herein, the authors report our cases. PMID:27065093

  8. Application of time-spatial labeling inversion pulse magnetic resonance imaging in the diagnosis of spontaneous intracranial hypotension due to high-flow cerebrospinal fluid leakage at C1-2

    PubMed Central

    Hattori, Natsuki; Inamasu, Joji; Nakae, Shunsuke; Hirose, Yuichi; Murayama, Kazuhiro

    2016-01-01

    Background: Spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid (CSF) leakage at C1-2 poses diagnostic and therapeutic challenges to spine surgeons. Although computed tomography (CT) myelography has been the diagnostic imaging modality of choice for identifying the CSF leakage point, extradural CSF collection at C1-2 on conventional CT myelography or magnetic resonance imaging (MRI) may often be a false localizing sign. Case Description: The present study reports the successful application of time-spatial labeling inversion pulse (T-SLIP) MRI, which enabled the precise identification of the CSF leakage point at C1-2 in a 28-year-old woman with intractable SIH. After identifying the leakage point using both CT myelography and T-SLIP MRI, surgery was performed to seal the CSF leak. Intraoperatively, a pouch suggestive of an extradural arachnoid cyst around the left C2 nerve root was found, which was repaired by packing the pouch with muscle and fibrin glue. Clinical improvement was observed shortly after surgery, and postoperative imaging revealed the disappearance of the CSF leakage. Conclusions: T-SLIP MRI may provide useful information on the flow dynamics of CSF in SIH patients due to high-flow leakage. However, further experience is required to assess its sensitivity and specificity as an imaging modality for identifying CSF leakage points. PMID:28144490

  9. Cerebrospinal fluid culture

    MedlinePlus

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

  10. Endoscopic repair of cerebrospinal fluid rhinorrhea.

    PubMed

    Kljajić, Vladimir; Vuleković, Petar; Vlaški, Ljiljana; Savović, Slobodan; Dragičević, Danijela; Papić, Vladimir

    Nasal liquorrhea indicates a cerebrospinal fluid fistula, an open communication between the intracranial cerebrospinal fluid and the nasal cavity. It can be traumatic and spontaneous. The aim of this study was to assess the outcome of endoscopic repair of cerebrospinal fluid fistula using fluorescein. This retrospective study included 30 patients of both sexes, with a mean age of 48.7 years, treated in the period from 2007 to 2015. All patients underwent lumbar administration of 5% sodium fluorescein solution preoperatively. Fistula was closed using three-layer graft and fibrin glue. Cerebrospinal fluid fistulas were commonly located in the ethmoid (37%) and sphenoid sinus (33%). Most patients presented with traumatic cerebrospinal fluid fistulas (2/3 of patients). The reported success rate for the first repair attempt was 97%. Complications occurred in three patients: one patient presented with acute hydrocephalus, one with reversible encephalopathy syndrome on the fifth postoperative day with bilateral loss of vision, and one patient was diagnosed with hydrocephalus two years after the repair of cerebrospinal fluid fistula. Endoscopic diagnosis and repair of cerebrospinal fluid fistulas using fluorescein intrathecally has high success rate and low complication rate. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. 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

  12. 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.

  13. Cerebrospinal fluid leaks following septoplasty.

    PubMed

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

    2014-12-01

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

  14. Assay of gentamicin in cerebrospinal fluid.

    PubMed Central

    Deacon, S

    1976-01-01

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

  15. Mollaret's meningitis associated with cerebrospinal fluid leak.

    PubMed

    Plit, M L; Miller, G B; Berkowitz, F E; Gear, J H

    1982-10-23

    Mollaret's meningitis or the benign recurrent meningitis syndrome is a rare disorder not previously described in Africa. The syndrome has a characteristic clinical presentation with spinal fluid pleocytosis, often with unusual 'epithelial' cells. With contemporary techniques no causative organism has been incriminated. The aetiology remains speculative, but we report on a patient found to have a cerebrospinal fluid leak, which may represent a factor in the pathogenesis of this disorder.

  16. 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

  17. Endonasal endoscopic closure of cerebrospinal fluid rhinorrhea.

    PubMed

    Schmerber, S; Righini, C; Lavielle, J P; Passagia, J G; Reyt, E

    2001-02-01

    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 (beta(2)-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.

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

    PubMed

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

    2013-09-17

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

  19. 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

  20. Fistula detection in cerebrospinal fluid leakage1

    PubMed Central

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

    1972-01-01

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

  1. Cerebrospinal fluid biomarkers in multiple sclerosis.

    PubMed

    Tumani, Hayrettin; Hartung, Hans-Peter; Hemmer, Bernhard; Teunissen, Charlotte; Deisenhammer, Florian; Giovannoni, Gavin; Zettl, Uwe K

    2009-08-01

    In patients with multiple sclerosis (MS) intensive efforts are directed at identifying biomarkers in bodily fluids related to underlying disease mechanisms, disease activity and progression, and therapeutic response. Besides MR imaging parameters cerebrospinal fluid (CSF) biomarkers provide important and specific information since changes in the CSF composition may reflect disease mechanisms inherent to MS. The different cellular and protein-analytical methods of the CSF and the recommended standard of the diagnostic CSF profile in MS are described. A brief update on possible CSF biomarkers that might reflect key pathological processes of MS such as inflammation, demyelination, neuroaxonal loss, gliosis and regeneration is provided.

  2. Cerebrospinal fluid tau proteins in status epilepticus.

    PubMed

    Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo F; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa

    2015-08-01

    Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Cerebrospinal fluid lactic acidosis in bacterial meningitis.

    PubMed Central

    Eross, J; Silink, M; Dorman, D

    1981-01-01

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

  4. [Cerebrospinal fluid diagnostics in multiple sclerosis].

    PubMed

    Ruprecht, K; Tumani, H

    2016-12-01

    As a chronic inflammatory disease of the central nervous system (CNS), multiple sclerosis (MS) is associated with characteristic abnormalities in cerebrospinal fluid (CSF). Thus, in addition to magnetic resonance imaging, CSF examination is a central diagnostic procedure in patients with MS, which can corroborate a diagnosis of MS and may also help to discern differential diagnoses. The most important CSF finding in MS is the detection of persistent polyspecific intrathecal immunoglobulin synthesis. This review summarizes CSF findings of patients with MS and addresses issues of relevance for clinical practice, potential diagnostic pitfalls as well as new developments in CSF diagnostics of MS.

  5. Burr Hole Drainage : Could Be Another Treatment Option for Cerebrospinal Fluid Leakage after Unidentified Dural Tear during Spinal Surgery?

    PubMed

    Huh, Jisoon

    2013-01-01

    Authors report a rare case of acute intracranial subdural and intraventricular hemorrhage that were caused by intracranial hypotension resulted from cerebrospinal fluid leakage through an unidentified dural tear site during spinal surgery. The initial brain computed tomography image showed acute hemorrhages combined with preexisting asymptomatic chronic subdural hemorrhage. One burr hole was made over the right parietal skull to drain intracranial hemorrhages and subsequent drainage of cerebrospinal fluid induced by closure of the durotomy site. Among various methods to treat cerebrospinal fluid leakage through unidentified dural injury site, primary repair and spinal subarachnoid drainage are well known treatment options. The brain imaging study to diagnose intracranial hemorrhage should be taken before selecting the treatment method, especially for spinal subarachnoid drainage. Similar mechanism to its spinal counterpart, cranial cerebrospinal fluid drainage has not been mentioned in previous article and could be another treatment option to seal off an unidentified dural tear in particular case of drainage of intracranial hemorrhage is needed.

  6. CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE

    PubMed Central

    Whedon, James M.; Glassey, Donald

    2010-01-01

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

  7. 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.

  8. Drug transport in brain via the cerebrospinal fluid

    PubMed Central

    2011-01-01

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

  9. Diagnostic value of circulating tumor cells in cerebrospinal fluid

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-09-01

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

  11. A new look at cerebrospinal fluid circulation.

    PubMed

    Brinker, Thomas; Stopa, Edward; Morrison, John; Klinge, Petra

    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.

  12. 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

  13. Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders

    PubMed Central

    Constantinescu, Radu; Mondello, Stefania

    2013-01-01

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

  14. 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). © The Author(s) 2016.

  15. [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.

  16. Cerebrospinal Fluid Biomarkers for Huntington's Disease.

    PubMed

    Byrne, Lauren M; Wild, Edward J

    2016-01-01

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

  17. Imhotep and the Discovery of Cerebrospinal Fluid

    PubMed Central

    Blomstedt, Patric

    2014-01-01

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

  18. Minimally invasive neurosurgery for cerebrospinal fluid disorders.

    PubMed

    Guillaume, Daniel J

    2010-10-01

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

  19. 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.

  20. 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.

  1. Elevated cerebrospinal fluid tau in Wernicke encephalopathy.

    PubMed

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

    2012-08-08

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

  2. 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.

  3. Cerebrospinal fluid eosinophilia in a child with neuroborreliosis.

    PubMed

    Buda, Piotr; Zawadka, Konrad; Wadowska-Kłopotek, Weronika; Smorczewska-Kiljan, Anna; Wieteska-Klimczak, Anna; Marczyńska, Magdalena; Książyk, Janusz

    2015-01-01

    Cerebrospinal fluid eosinophilia is rare and usually associated with eosinophilic meningitis caused by helminthic infections. It is also observed in bacterial or fungal meningitis (syphilis, tuberculosis, coccidioidomycosis), in patients with malignancies, ventriculoperitonial shunts, hypereosinophilic syndrome or allergy to some medications. Here we present a case of an 8-year-old boy admitted with fever and clinical signs of meningitis. Cerebrospinal fluid (CSF) analysis showed marked eosinophilia. Basing on further serological CSF testing the diagnosis of borreliosis was established. Cerebrospinal fluid eosinophilia in Borrelia burgdorferi infection has never been reported before.

  4. Oxygenation of the cerebrospinal fluid with artificial cerebrospinal fluid can ameliorate a spinal cord ischemic injury in a rabbit model.

    PubMed

    Kanda, Keisuke; Adachi, Osamu; Kawatsu, Satoshi; Sakatsume, Ko; Kumagai, Kiichiro; Kawamoto, Shunsuke; Saiki, Yoshikatsu

    2016-11-01

    We evaluated the effect of cerebrospinal fluid oxygenation for the prevention of spinal cord ischemic injury after infrarenal aortic occlusion in a rabbit model. Twenty white Japanese rabbits were categorized into the following 4 groups (5 in each): group S (sham), balloon catheter insertion on to the aorta; group C (control), spinal cord ischemic injury by infrarenal abdominal aortic balloon occlusion for 15 minutes; group N (nonoxygenated), spinal cord ischemic injury with cerebrospinal fluid replacement by nonoxygenated artificial cerebrospinal fluid; and group O (oxygenated), spinal cord ischemic injury with cerebrospinal fluid replacement by nanobubble-oxygenated artificial cerebrospinal fluid. The changes in cerebrospinal fluid partial pressure of oxygen during the peri-ischemic period, modified Tarlov score, and histopathology of the spinal cord 48 hours after aortic maneuvers were evaluated. Cerebrospinal fluid partial pressure of oxygen significantly increased in group O compared with group N after cerebrospinal fluid replacement (254.5 ± 54.8 mm Hg vs 136.1 ± 43.5 mm Hg, P = .02). After 15 minutes of spinal cord ischemic injury, cerebrospinal fluid partial pressure of oxygen in group C decreased to 65.8 ± 18.6 mm Hg compared with baseline (148.8 ± 20.6 mm Hg, P < .01), whereas cerebrospinal fluid partial pressure of oxygen in group O was maintained at remarkably high levels after spinal cord ischemic injury (291.9 ± 51.8 mm Hg), which was associated with improved neurologic function, with 20% of spinal cord ischemic injury having a Tarlov score less than 5 compared with 100% of spinal cord ischemic injury in group C. Preservation of anterior horn neurons in groups N and O was confirmed by histopathologic analysis with significant reduction of degenerated neurons compared with group C. Cerebrospinal fluid oxygenation with artificial cerebrospinal fluid can exert a protective effect against spinal cord ischemic injury in rabbits

  5. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Quantitative evaluation fo cerebrospinal fluid shunt flow

    SciTech Connect

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

    1984-01-01

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

  7. Doxepin concentrations in plasma and cerebrospinal fluid.

    PubMed

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

    2011-04-01

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

  8. 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.

  9. Analysis of extracellular RNA in cerebrospinal fluid

    PubMed Central

    Saugstad, Julie A.; Lusardi, Theresa A.; Van Keuren-Jensen, Kendall R.; Phillips, Jay I.; Lind, Babett; Harrington, Christina A.; McFarland, Trevor J.; Courtright, Amanda L.; Reiman, Rebecca A.; Yeri, Ashish S.; Kalani, M. Yashar S.; Adelson, P. David; Arango, Jorge; Nolan, John P.; Duggan, Erika; Messer, Karen; Akers, Johnny C.; Galasko, Douglas R.; Quinn, Joseph F.; Carter, Bob S.; Hochberg, Fred H.

    2017-01-01

    ABSTRACT We examined the extracellular vesicle (EV) and RNA composition of pooled normal cerebrospinal fluid (CSF) samples and CSF from five major neurological disorders: Alzheimer’s disease (AD), Parkinson’s disease (PD), low-grade glioma (LGG), glioblastoma multiforme (GBM), and subarachnoid haemorrhage (SAH), representing neurodegenerative disease, cancer, and severe acute brain injury. We evaluated: (I) size and quantity of EVs by nanoparticle tracking analysis (NTA) and vesicle flow cytometry (VFC), (II) RNA yield and purity using four RNA isolation kits, (III) replication of RNA yields within and between laboratories, and (IV) composition of total and EV RNAs by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing (RNASeq). The CSF contained ~106 EVs/μL by NTA and VFC. Brain tumour and SAH CSF contained more EVs and RNA relative to normal, AD, and PD. RT-qPCR and RNASeq identified disease-related populations of microRNAs and messenger RNAs (mRNAs) relative to normal CSF, in both total and EV fractions. This work presents relevant measures selected to inform the design of subsequent replicative CSF studies. The range of neurological diseases highlights variations in total and EV RNA content due to disease or collection site, revealing critical considerations guiding the selection of appropriate approaches and controls for CSF studies. PMID:28717417

  10. Endoscopic management of cerebrospinal fluid rhinorrhea

    PubMed Central

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

    2016-01-01

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

  11. Cerebellar hemorrhage caused by cerebrospinal fluid leak after spine surgery.

    PubMed

    Farag, Ehab; Abdou, Amgad; Riad, Ihab; Borsellino, Sam R; Schubert, Armin

    2005-02-01

    Spine surgery is associated with a wide range of surgical and anesthetic complications. Excessive cerebrospinal fluid leak can be a cause of cerebellar hemorrhage postoperatively. We report a 43-yr-old patient who had lumbar spine reexploration surgery complicated by a cerebrospinal fluid leak which led to cerebellar hemorrhage manifested by postoperative mental status changes. Early detection and proper management resulted in full recovery.

  12. Quantitative proteomics of delirium cerebrospinal fluid

    PubMed Central

    Poljak, A; Hill, M; Hall, R J; MacLullich, A M; Raftery, M J; Tai, J; Yan, S; Caplan, G A

    2014-01-01

    Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis. PMID:25369144

  13. Cerebrospinal fluid dynamics study in communicating hydrocephalus.

    PubMed

    Ramesh, Vengalathur Ganesan; Narasimhan, Vidhya; Balasubramanian, Chandramouli

    2017-01-01

    Communicating hydrocephalus often poses a challenge in diagnosis and management decisions. The objective of this study is to measure the opening pressure (Po), pressure volume index (PVI), and cerebrospinal fluid outflow resistance (Rout), in patients with communicating hydrocephalus using bolus lumbar injection method and to evaluate its diagnostic and prognostic value. The study was conducted in 50 patients with communicating hydrocephalus, including normal pressure hydrocephalus (NPH) (19), post-meningitic hydrocephalus (23) and post-traumatic hydrocephalus (8). An improvised bolus lumbar injection method [the Madras Institute of Neurology (MIN) method] was used. In the NPH Group, the CSF dynamics studies correlated well with the clinico-radiological classification. The prediction of shunt responsiveness by CSF dynamics studies correlated with good outcome in 87.5%. In the post-meningitic hydrocephalus group, the value of CSF dynamics studies in predicting patients needing shunt was 89.5%. The CSF dynamics studies detected patients who needed shunt earlier than clinical or radiological indications. In the post-traumatic hydrocephalus group, 62.5% of patients improved with the treatment based on CSF dynamics studies. The improvised bolus lumbar injection method (MIN method) is a very simple test with fairly reliable and reproducible results. Study of CSF dynamics is a valuable tool in communicating hydrocephalus for confirmation of diagnosis and predicting shunt responsiveness. This is the first time that the value of CSF dynamics has been studied in patients with post-meningitic hydrocephalus. It was also useful for early selection of cases for shunting and for identifying patients with atrophic ventriculomegaly, thereby avoiding unnecessary shunt.

  14. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus

    PubMed Central

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

    2017-01-01

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

  15. Subcommissural organ, cerebrospinal fluid circulation, and hydrocephalus.

    PubMed

    Pérez-Fígares, J M; Jimenez, A J; Rodríguez, E M

    2001-03-01

    Under normal physiological conditions the cerebrospinal fluid (CSF) is secreted continuously, although this secretion undergoes circadian variations. Mechanisms operating at the vascular side of the choroidal cells involve a sympathetic and a cholinergic innervation, with the former inhibiting and the latter stimulating CSF secretion. There are also regulatory mechanisms operating at the ventricular side of the choroidal cells, where receptors for monoamines such as dopamine, serotonin, and melatonin, and for neuropeptides such as vasopressin, atrial natriuretic hormone, and angiotensin II, have been identified. These compounds, that are normally present in the CSF, participate in the regulation of CSF secretion. Although the mechanisms responsible for the CSF circulation are not fully understood, several factors are known to play a role. There is evidence that the subcommissural organ (SCO)--Reissner's fiber (RF) complex is one of the factors involved in the CSF circulation. In mammals, the predominant route of escape of CSF into blood is through the arachnoid villi. In lower vertebrates, the dilatation of the distal end of the central canal, known as terminal ventricle or ampulla caudalis, represents the main site of CSF escape into blood. Both the function and the ultrastructural arrangement of the ampulla caudalis suggest that it may be the ancestor structure of the mammalian arachnoid villi. RF-glycoproteins reaching the ampulla caudalis might play a role in the formation and maintenance of the route communicating the CSF and blood compartments. The SCO-RF complex may participate, under physiological conditions, in the circulation and reabsorption of CSF. Under pathological conditions, the SCO appears to be involved in the pathogeneses of congenital hydrocephalus. Changes in the SCO have been described in all species developing congenital hydrocephalus. In these reports, the important question whether the changes occurring in the SCO precede hydrocephalus, or

  16. Sarcoid meningitis with fulminant delirium and markedly abnormal cerebrospinal fluid.

    PubMed

    Noble, James M; Anderson, Christopher Todd; Etienne, Mill; Williams, Olajide; Adams, David J

    2007-01-01

    To describe a patient with an acute fulminant delirium and eventual spinal fluid block secondary to sarcoid meningitis. Case report. Hospital and Neurology Clinic. A previously healthy, 24-year-old man. Antimicrobials, corticosteroids, lumbar puncture, myelography, and lymph node biopsy. Cerebrospinal fluid, clinical status. The patient improved after treatment with corticosteroids. Sarcoid meningitis may present with delirium and spinal block.

  17. New techniques and technology to repair cerebrospinal fluid rhinorrhea.

    PubMed

    Paludetti, G; Sergi, B; Rigante, M; Campioni, P; Galli, J

    2004-06-01

    Cerebrospinal fluid rhinorrhea occurs as a result of abnormal communication between the subarachnoid space and the pneumatized portion of the skull base, the paranasal sinuses and the middle ear. Conservative measures may be sufficient in the management of cerebrospinal fluid rhinorrhea, but, in some cases, surgical treatment may be required. Transnasal endoscopic techniques are constantly being used in preference to the intra- and extracranial approaches. Recently, image guidance systems have been adopted in neurosurgery, skull base and paranasal sinus surgery. The present report refers to 4 cases of nasal cerebrospinal fluid rhinorrhea leak successfully treated with a transnasal endoscopic approach using various techniques and materials to close the bone defect, in 2 of which, the navigation system (Stealth Station Treon ENT Image Guidance System with Landmark X, Software, Medtronic, XOMED, Jacksonville, FL, USA) was also used. In all cases, correct localization and repair of the leak was achieved and no major complications occurred. Following a review of the literature, the Authors conclude that, at present, transnasal endoscopic repair of cerebrospinal fluid rhinorrhea is the surgical treatment of choice when the techniques and materials are correctly used. Furthermore, preliminary findings indicate that it is possible to make routine use of the navigation systems and that this technology may be usefully employed, above all, in the management of cerebrospinal fluid leaks.

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

    PubMed

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

    2011-07-01

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

  19. 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

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

    PubMed

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

    2017-03-01

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

  1. 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

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    1998-01-01

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

  4. MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage.

    PubMed

    Bache, Søren; Rasmussen, Rune; Rossing, Maria; Laigaard, Finn Pedersen; Nielsen, Finn Cilius; Møller, Kirsten

    2017-09-01

    Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. In a prospective case-control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians. MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients (P<0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without (P<0.05) in both the screening and validation. SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791257. © 2017 The Authors.

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

    PubMed

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

    1994-07-01

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

  6. Entamoeba histolytica meningoencephalitis diagnosed by trophozoites in cerebrospinal fluid

    PubMed Central

    Goh, L M L; Marrone, J R

    2013-01-01

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

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

    PubMed

    Goh, L M L; Marrone, J R

    2013-10-01

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

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

    PubMed Central

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

    1973-01-01

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

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

    PubMed

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

    2017-10-01

    Cutaneous fistula of cerebrospinal fluid is a rare complication of neuroaxial blockade. We report the case of a parturient in whom an epidural catheter was placed for labour analgesia and 12h after the catheter was removed, presented an abundant asymptomatic fluid leak from the puncture site, compatible in the cyto-chemical analysis with cerebrospinal fluid. She was treated with acetazolamide, compression of skin orifice of the fluid leakage, antibiotic prophylaxis, hydration and rest, and progressed satisfactorily without requiring blood patch. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. 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)

  11. 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)

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

    PubMed

    Son, Byung-Chul; Ha, Sang-Woo; Lee, Si-Hoon; Choi, Jin-Gyu

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Interpretation of Cerebrospinal Fluid White Blood Cell Counts in Young Infants With a Traumatic Lumbar Puncture.

    PubMed

    Lyons, Todd W; Cruz, Andrea T; Freedman, Stephen B; Neuman, Mark I; Balamuth, Fran; Mistry, Rakesh D; Mahajan, Prashant; Aronson, Paul L; Thomson, Joanna E; Pruitt, Christopher M; Shah, Samir S; Nigrovic, Lise E

    2017-05-01

    We determine the optimal correction factor for cerebrospinal fluid WBC counts in infants with traumatic lumbar punctures. We performed a secondary analysis of a retrospective cohort of infants aged 60 days or younger and with a traumatic lumbar puncture (cerebrospinal fluid RBC count ≥10,000 cells/mm(3)) at 20 participating centers. Cerebrospinal fluid pleocytosis was defined as a cerebrospinal fluid WBC count greater than or equal to 20 cells/mm(3) for infants aged 28 days or younger and greater than or equal to 10 cells/mm(3) for infants aged 29 to 60 days; bacterial meningitis was defined as growth of pathogenic bacteria from cerebrospinal fluid culture. Using linear regression, we derived a cerebrospinal fluid WBC correction factor and compared the uncorrected with the corrected cerebrospinal fluid WBC count for the detection of bacterial meningitis. Of the eligible 20,319 lumbar punctures, 2,880 (14%) were traumatic, and 33 of these patients (1.1%) had bacterial meningitis. The derived cerebrospinal fluid RBCs:WBCs ratio was 877:1 (95% confidence interval [CI] 805 to 961:1). Compared with the uncorrected cerebrospinal fluid WBC count, the corrected one had lower sensitivity for bacterial meningitis (88% uncorrected versus 67% corrected; difference 21%; 95% CI 10% to 37%) but resulted in fewer infants with cerebrospinal fluid pleocytosis (78% uncorrected versus 33% corrected; difference 45%; 95% CI 43% to 47%). Cerebrospinal fluid WBC count correction resulted in the misclassification of 7 additional infants with bacterial meningitis, who were misclassified as not having cerebrospinal fluid pleocytosis; only 1 of these infants was older than 28 days. Correction of the cerebrospinal fluid WBC count substantially reduced the number of infants with cerebrospinal fluid pleocytosis while misclassifying only 1 infant with bacterial meningitis of those aged 29 to 60 days. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All

  15. Quantitation of free light chains in the cerebrospinal fluid reliably predicts their intrathecal synthesis.

    PubMed

    Zeman, David; Kušnierová, Pavlína; Bartoš, Vladimír; Hradílek, Pavel; Kurková, Barbora; Zapletalová, Olga

    2016-01-01

    The results of free light chains quantitation in the cerebrospinal fluid were recently compared with the presence of cerebrospinal fluid-restricted oligoclonal IgG, but not oligoclonal free kappa light chains and oligoclonal free lambda light chains. We therefore aimed to compare the performance of the quantitative tests with the qualitative one for the same molecule. Seventy-five paired cerebrospinal fluid and serum samples were analysed for oligoclonal IgG, oligoclonal free kappa light chains and oligoclonal free lambda light chains. Cerebrospinal fluid and serum free kappa and lambda light chains were quantified using Freelite™ kits on SPA Plus analyzer. ROC curves were analysed for the prediction of intrathecal synthesis and compared for cerebrospinal fluid concentration, cerebrospinal fluid/serum quotient (QfLC) and index (QfLC/QAlbumin). The presence of cerebrospinal fluid-restricted oligoclonal free kappa light chains and oligoclonal free lambda light chains bands was used as reference. No statistically significant differences were observed among cerebrospinal fluid concentration, QfLC and index for the prediction of free light chain intrathecal synthesis. Each parameter was able to predict the occurrence of cerebrospinal fluid-restricted oligoclonal free light chain bands (AUCs 0.932-0.999). However, we noted elevated cerebrospinal fluid free light chain concentrations in the absence of cerebrospinal fluid-restricted oligoclonal free light chain bands in two patients with very high serum free light chain values. Quantitation of cerebrospinal fluid free light chains reliably predicts their intrathecal synthesis. Yet, cerebrospinal fluid/serum quotient may still be preferred to correct for high serum free light chain concentrations. An appropriate formula should be sought to correct for blood-cerebrospinal fluid barrier status. © The Author(s) 2015.

  16. Cerebrospinal fluid drainage options for posthemorrhagic hydrocephalus in premature neonates.

    PubMed

    Melo, José Roberto Tude; Passos, Rosane Klein; Carvalho, Marcelo Liberato Coelho Mendes de

    2017-07-01

    The literature describes various cerebrospinal fluid (CSF) drainage techniques to alleviate posthemorrhagic hydrocephalus in preterm newborns; however, consensus has not been reached. The scope of this study was describing a case series of premature neonates with posthemorrhagic hydrocephalus and assessing the outcomes of different approaches used for CSF diversion. A consecutive review of the medical records of neonates with posthemorrhagic hydrocephalus treated with CSF drainage was conducted. Forty premature neonates were included. Serial lumbar puncture, ventriculosubgaleal shunt, and ventriculoperitoneal shunt were the treatments of choice in 25%, 37.5% and 37.5% of the cases, respectively. Cerebrospinal fluid diversion should be tailored to each case with preference given to temporary CSF drainage in neonates with lower age and lower birth-weight, while the permanent ventriculoperitoneal shunt should be considered in healthier, higher birth-weight neonates born closer to term.

  17. Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer’s disease

    PubMed Central

    Fagan, Anne M; Perrin, Richard J

    2012-01-01

    Dementia due to Alzheimer’s disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current AD clinical diagnosis, biomarkers of AD pathologies are currently being sought. Reductions in cerebrospinal fluid levels of β-amyloid 42 (a marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are well-established as biomarkers useful for AD diagnosis and prognosis. However, novel markers for other features of AD pathophysiology (e.g., β-amyloid processing, neuroinflammation and neuronal stress/dysfunction) and for other non-AD dementias are required to improve the accuracy of AD disease diagnosis, prognosis, staging and therapeutic monitoring (theragnosis). This article discusses the potential of several promising novel cerebrospinal fluid analytes, highlights the next steps critical for advancement in the field, and provides a prediction on how the field may evolve in 5–10 years. PMID:22917147

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

    PubMed

    Yamada, Shinya; Kelly, Erin

    2016-04-01

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

  19. Cerebrospinal fluid involvement in acute promyelocytic leukaemia at presentation

    PubMed Central

    Mishra, Jyoti; Gupta, Mayank

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2007-03-01

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

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

    PubMed

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

    2008-07-01

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

  3. Cerebrospinal fluid rhinorrhea and unilateral nasal polyposis: a case report.

    PubMed

    Gallina, E; Gallo, O; Bottai, G V; Ammannati, F

    1990-01-01

    We report a case of cerebrospinal fluid (CSF) rhinorrhea and unilateral polyposis in a 53-year-old woman. The clinical features, tomograms, and CT scan with Metrizamide infusion are examined. The analysis of this case evidences that: 1) A CSF can occur also after a long time (3 years) following a head injury; 2) CT cisternography with Metrizamide can demonstrate a leakage, but not always the fluid egress from the intracranial cavity; and 3) A CSF rhinorrhea may be the primary cause and not an occasional association or complication of a reactive phlogistic nasal disease.

  4. Vanishing calcification associated with a spontaneous ventral spinal cerebrospinal fluid leak.

    PubMed

    Schievink, Wouter I; Ross, Lindsey; Prasad, Ravi S; Maya, M Marcel

    2016-12-01

    Some patients with spontaneous intracranial hypotension have a ventral spinal cerebrospinal fluid (CSF) leak and these CSF leaks may be associated with calcified disk herniations. Identifying these calcifications is helpful in directing treatment. We report here the unusual case of a patient with a ventral CSF leak in whom the associated calcification absorbed over a five-month period. A 42-year-old woman developed orthostatic headaches and bilateral abducens nerve palsies. Magnetic resonance imaging of her brain showed typical findings of spontaneous intracranial hypotension. Magnetic resonance imaging of her spine showed an extensive cervicothoracic CSF leak. Computed tomographic myelography showed calcification at the Th1-2 disk space. Three epidural blood patches were performed, but her symptoms persisted. Digital subtraction myelography performed five months later showed an upper thoracic ventral CSF, but the calcification was no longer present. A dural tear, found at surgery at the Th1-2 level, was repaired and the patient made an uneventful recovery. The resorption of calcifications at the level of a ventral spinal CSF leak could explain the absence of any calcifications in at least some patients with such leaks and demonstrates the usefulness of reviewing previous imaging in patients with ventral CSF leaks if the exact site of the leak remains unknown. © International Headache Society 2016.

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

    PubMed

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

    2011-12-01

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

  6. Cerebrospinal fluid eosinophilia associated with intraventricular shunts.

    PubMed

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

    2011-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Chemokine CXCL13 concentration in cerebrospinal fluid in patients with neuroborreliosis--own observations.

    PubMed

    Kępa, Lucjan; Oczko-Grzesik, Barbara; Sobala-Szczygieł, Barbara; Boroń-Kaczmarska, Anna

    2015-01-01

    of the study was to evaluate the usefulness of cerebrospinal fluid chemokine CXCL13 concentration assay in diagnostics of neuroborreliosis in adults. Investigations were carried out in 22 patients treated for neuroborreliosis , manifested as lymphocytic meningitis, at the Department of Infectious Diseases, Medical University of Silesia, in Bytom between 2011-2013. Based on the presence or absence of anti-borrelial antibodies in the cerebrospinal fluid, the examined individuals were divided into two groups on the day of admission: group I--patients with antiborrelial antibodies in the cerebrospinal fluid (confirmed diagnosis of neuroborreliosis), group II--patients without antiborrelial antibodies in the cerebrospinal fluid (possible diagnosis of neuroborreliosis). In all patients the cerebrospinal fluid CXCL13 level was assessed on the first day of hospitalization. Control tests were performed in both groups after 14 days of therapy with antibiotics. Mean cerebrospinal fluid CXCL13 concentration in group I on the 1st day was 4123 pg/mL, and in group II--3422 pg/mL. Differences in mean concentrations of this chemokine were statistically insignificant. No correlations between examined mean CXCL13 concentrations and other cerebrospinal fluid inflammatory parameters were revealed. The control tests showed the evident decrease of CXCL13 level in cerebrospinal fluid in both groups. Besides, in individuals of group II anti-Borrelia burgdorferi antibodies appeared in cerebrospinal fluid, whereas in group I, the control results of this parameter were similar to preliminary values. The obtained results indicate a kind of usefulness of estimation of cerebrospinal fluid chemokine CXCL13 concentration in diagnostics of early, acute neuroborreliosis, manifested as lymphocytic meningitis, especially in case of anti-borrelia antibodies absence in cerebrospinal fluid. Changes in this chemokine concentrations, opposite to cerebrospinal fluid levels of anti-borrelia antibodies, may

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

    PubMed

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

    2009-12-01

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

  10. 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

  11. 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.

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

    PubMed

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

    1995-11-27

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

  13. Cerebrospinal Fluid and Hydrocephalus: Physiology, Diagnosis, and Treatment.

    PubMed

    Filis, Andreas K; Aghayev, Kamran; Vrionis, Frank D

    2017-01-01

    Cerebrospinal fluid (CSF) is found around and inside the brain and vertebral column. CSF plays a crucial role in the protection and homeostasis of neural tissue. Key points on the physiology of CSF as well as the diagnostic and treatment options for hydrocephalus are discussed. Understanding the fundamentals of the production, absorption, dynamics, and pathophysiology of CSF is crucial for addressing hydrocephalus. Shunts and endoscopic third ventriculostomy have changed the therapeutic landscape of hydrocephalus. The treatment of hydrocephalus in adults and children represents a large part of everyday practice for the neurologist, both in benign cases and cancer-related diagnoses.

  14. [Strategies for cerebrospinal fluid analysis - Integrated results report].

    PubMed

    Uhr, M; Tumani, H; Lange, P

    2016-12-01

    Cerebrospinal fluid (CSF) analysis requires a combined assessment of all individual test findings in an integrated total report in order to achieve a reliable and specific diagnostic conclusion. Such a standard assessment strategy allows the identification of disease-typical result patterns and plausibility checks to avoid analytical errors. The integrated total report consists of 1) a basic CSF program with cytological and protein chemical parameters, 2) an expanded CSF program with special parameters for detection of pathogens and markers of neurodegeneration and 3) a final contextual interpretation considering methodological and clinical aspects.

  15. Methods for chromatofocusing of cerebrospinal fluid and serum immunoglobulin G.

    PubMed

    Gallo, P; Olsson, O; Sidén, A

    1985-06-26

    Chromatofocusing programs were designed for separations of submilligram amounts of normal and abnormal human IgG. The Pharmacia FPLC system, equipped with a Mono P column or a specially designed, small column was used for the separations. Normal IgG in paired cerebrospinal fluid and serum samples, paired samples from patients with intrathecal immunoglobulin G synthesis, as well as sera with IgG M components were examined. Abnormal immunoglobulin G components, especially those with pI values greater than ca. 7.0 pH units, were easily identified.

  16. Entamoeba histolytica encephalitis diagnosed by PCR of cerebrospinal fluid.

    PubMed

    Solaymani-Mohammadi, Shahram; Lam, Maggie M; Zunt, Joseph R; Petri, William A

    2007-03-01

    Extra-intestinal amebiasis is secondary to invasive intestinal infections and usually results in an amebic liver abscess. Other organs, including lungs, brain, skin, spleen and kidneys, may be involved. Diagnosis of the cerebral infection is of the utmost importance and is most often made by detection of the organism at the time of brain biopsy or at autopsy. We report the first case of Entamoeba histolytica encephalitis diagnosed by PCR of the cerebrospinal fluid. The patient was treated successfully with metronidazole. PCR is an increasingly useful tool for the diagnosis of central nervous system infection and can provide rapid diagnosis.

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

    PubMed

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

    2017-01-01

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

  18. Pathogenesis of non-traumatic cerebrospinal fluid rhinorrhea.

    PubMed

    Bjerre, P; Lindholm, J; Gyldensted, C

    1982-08-01

    15 consecutive patients with non-traumatic cerebrospinal fluid rhinorrhea were studied. 13 operations were performed on 10 patients. In 8 transcranial operations, an assumed defect in the anterior fossa was plugged with muscle, but only 3 operations were successful. In 4 operations, either transcranial or transsphenoidal, the sella was packed with muscle and rhinorrhea ceased immediately. Based on radiological and operative findings, 3 groups of patients appeared (1) 9 patients had pathology related to the pituitary gland or the sella turcica: enlarged sella, empty sella, pituitary tumour, intrasellar cyst or erosion of the sellar osseous border. (2) 2 patients had rhinorrhea from extrasellar origin. (3) In 4 patients no abnormality could be found. Prior to the rhinorrhea, 6 patients (5 from group 1 and 1 from group 3) had experienced episodes of neurological symptoms, compatible with a pituitary apoplexy. It is suggested that non-traumatic cerebrospinal fluid rhinorrhea in most cases is the result of a spontaneous necrosis in a pituitary adenoma, which has caused sellar bony erosion.

  19. Extremely rare complications in cerebrospinal fluid shunt operations.

    PubMed

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

    2002-06-01

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

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

    PubMed

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

    2012-12-01

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

  1. 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.

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

    PubMed Central

    2010-01-01

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

  3. 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

  4. 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.

  5. Spectrophotometry of cerebrospinal fluid in subacute and chronic subdural haematomas

    PubMed Central

    Kjellin, K. G.; Steiner, L.

    1974-01-01

    Spectrophotometric examinations were performed on cerebrospinal and subdural fluids in subacute (five patients) and chronic (20 patients) subdural haematomas, with special reference to the diagnostic aid of CSF spectrophotometry. Spectrophotometric xanthochromia of haemorrhagic origin was found in all CSFs examined, while definite visible xanthochromia was observed in only 28% and the CSF was judged as colourless in 52% of those cases. Characteristic bleeding patterns were found spectrophotometrically in all the 20 CSFs examined within 24 hours after lumbar puncture, haematoma patterns being detected in 90-95% of the cases. In many cases the electrophoretically separated protein fractions of CSF and subdural fluids were spectrophotometrically examined. In conclusion, CSF spectrophotometry is a simple, fast, and extremely sensitive method, which in our opinion should be used routinely in the diagnosis of suspected subdural haematomas, if lumbar puncture is not contraindicated. PMID:4140892

  6. Correction of Cerebrospinal Fluid Protein in Infants With Traumatic Lumbar Punctures.

    PubMed

    Lyons, Todd W; Cruz, Andrea T; Freedman, Stephen B; Arms, Joseph L; Aronson, Paul L; Fleming, Alesia H; Kulik, Dina M; Mahajan, Prashant; Mistry, Rakesh D; Pruitt, Christopher M; Thompson, Amy D; Nigrovic, Lise E

    2017-10-01

    In our multicenter cohort of infants ≤60 days of age, we identified 2646 infants with a traumatic lumbar puncture, of which 31 (1.2%) had bacterial meningitis. For every 1000 cerebrospinal fluid red blood cells/mm, cerebrospinal (cerebrospinal fluid) protein increased 1.1 mg/dL (95% confidence interval: 1.0-1.2 mg/dL).

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

    NASA Astrophysics Data System (ADS)

    Staroń, Waldemar; Herbowski, Leszek; Gurgul, Henryk

    2007-04-01

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

  8. Floating dural sac sign is a sensitive magnetic resonance imaging finding of spinal cerebrospinal fluid leakage.

    PubMed

    Hosoya, Takaaki; Hatazawa, Jun; Sato, Shinya; Kanoto, Masafumi; Fukao, Akira; Kayama, Takamasa

    2013-01-01

    We would like to propose floating dural sac sign, which is observed as a hyperintense band or rim around the spinal dural sac on axial T2-weighted images, as a sensitive sign to identify cerebrospinal fluid (CSF) leakage. One hundred patients with orthostatic headache were prospectively registered in 11 hospitals. These patients were examined by brain magnetic resonance (MR) imaging (n = 89), radioisotope cisternography (n = 89), MR myelography (n = 86), axial T2-weighted imaging of the spine (n = 70), and computed tomography myelography (n = 2). In this study, we separately evaluated the imaging findings of intracranial hypotension and spinal CSF leakage. Among 100 patients, 16 patients were diagnosed as having spinal CSF leaks. Of 70 patients examined with axial T2-weighted imaging, 14 patients were diagnosed with spinal CSF leaks, and floating dural sac sign was observed in 17 patients, 13 patients with spinal CSF leaks and 4 without CSF leaks (sensitivity 92.9%, specificity 92.9%). Of 86 patients examined by MR myelography, extradural fluid was observed in only 3 patients (sensitivity 21.4%, specificity 100%). The floating dural sac sign was a sensitive sign that can be used to identify CSF leakage. Spinal axial T2-weighted imaging might be a good screening method for spinal CSF leakage that can help to avoid the need for lumbar puncture.

  9. Dinosaur Tail Sign: A Useful Spinal MRI Finding Indicative of Cerebrospinal Fluid Leakage.

    PubMed

    Sakurai, Keita; Kanoto, Masafumi; Nakagawa, Motoo; Shimohira, Masashi; Tokumaru, Aya M; Kameyama, Masashi; Shimoji, Keigo; Morimoto, Satoru; Matsukawa, Noriyuki; Nishio, Minoru; Shibamoto, Yuta

    2017-06-01

    To evaluate the imaging characteristics and diagnostic utility of the "Dinosaur tail sign" in the diagnosis of cerebrospinal fluid (CSF) leakage. The authors propose the "Dinosaur tail sign," defined as a combination of the dorsal epidural hyperintensities, fat tissue, spinal cord, and cauda equine on lumbosacral sagittal fat-suppressed T2-weighted image (FST2WI), as a sensitive indicator for diagnosing CSF leakage. Imaging characteristics of the "Dinosaur tail sign" was evaluated in seven spontaneous intracranial hypotension (SIH) and 23 iatrogenic CSF leakage (ICSFL) patients. Additionally, the diagnostic index was compared between the "Dinosaur tail sign" and other previously reported useful magnetic resonance imaging (MRI) and magnetic resonance myelography (MRM) findings. In contrast to other imaging findings including the epidural expansion, floating dural sac sign, and distension of the spinal epidural veins on MRI, and paraspinal fluid collections (PFC) on MRM, the "Dinosaur tail sign" was found equally in both SIH and ICSFL patients (6 SIH and 19 ICSFL; 83% of all patients with CSF leakage). The "Dinosaur tail sign" showed sufficient diagnostic utility (sensitivity 83%, specificity 94%, accuracy 89%) that was comparable to that of PFC. The "Dinosaur tail sign" is a useful imaging finding suggestive of CSF leakage. Evaluation of subtle interspinous arched hyperintensities on spinal MRI is mandatory for the diagnosis of SIH and ICSFL. © 2017 American Headache Society.

  10. Cerebrospinal fluid outflow resistance as a diagnostic marker of spontaneous cerebrospinal fluid leakage.

    PubMed

    Beck, Jürgen; Fung, Christian; Ulrich, Christian T; Fiechter, Michael; Fichtner, Jens; Mattle, Heinrich P; Mono, Marie-Luise; Meier, Niklaus; Mordasini, Pasquale; Z'Graggen, Werner J; Gralla, Jan; Raabe, Andreas

    2017-08-01

    OBJECTIVE Spinal CSF leakage causes spontaneous intracranial hypotension (SIH). The aim of this study was to characterize CSF dynamics via lumbar infusion testing in patients with and without proven spinal CSF leakage in order to explore possible discriminators for the presence of an open CSF leak. METHODS This analysis included all patients with suspected SIH who were treated at the authors' institution between January 2012 and February 2015. The gold standard for "proven" CSF leakage is considered to be extrathecal contrast accumulation after intrathecal contrast injection. To characterize CSF dynamics, the authors performed computerized lumbar infusion testing to measure lumbar pressure at baseline (opening pressure) and at plateau, as well as pulse amplitude, CSF outflow resistance (RCSF), craniospinal elastance, and pressure-volume index. RESULTS Thirty-one patients underwent clinical imaging and lumbar infusion testing and were included in the final analysis. A comparison of the 14 patients with proven CSF leakage with the 17 patients without leakage showed a statistically significantly lower lumbar opening pressure (p < 0.001), plateau pressure (p < 0.001), and RCSF (p < 0.001) in the group with leakage. Sensitivity, specificity, and positive and negative predictive values for an RCSF cutoff of ≤ 5 mm Hg/(ml/min) were 0.86, 1.0, 1.0, and 0.89 (area under the curve of 0.96), respectively. The median pressure-volume index was higher (p = 0.003), and baseline (p = 0.017) and plateau (p < 0.001) pulse amplitudes were lower in patients with a proven leak. CONCLUSIONS Lumbar infusion testing captures a distinct pattern of CSF dynamics associated with spinal CSF leakage. RCSF assessed by computerized lumbar infusion testing has an excellent diagnostic accuracy and is more accurate than evaluating the lumbar opening pressure. The authors suggest inclusion of RCSF in the diagnostic criteria for SIH.

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

    PubMed

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

    2016-12-01

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

  12. [The characteristics and treatment of empty sella combined cerebrospinal fluid leakage of nasal].

    PubMed

    Zhai, Xiang; Zhang, Jinling; Liu, Gang

    2012-12-01

    To study the feature and treatment method of patients with empty sella merger cerebro-spinal fluid leakage of nasal. There were 8 cases with empty sella merger cerebrospinal fluid leakage of nasal, 2 cases were accepted the repairing surgery of cerebrospinal fluid leakage one time, 4 cases were accepted the repairing surgery of cerebrospinal fluid leakage used endoscope 2 times, 1 case was accepted repairing surgery of cerebrospinal fluid leakage used endoscope merge craniotomy and ventricle celiac bypass, 1 case recurrences after repairing surgery of cerebrospinal fluid was recurred after conservative treatment. Some postoperative were stayed in bed for three weeks and lumbar drainage for 1 week. One case of cerebral hemorrhage after surgery was cured with craniotomy, followed for 2 years without recurrence. One case was recurred after conservative treatment. Two cases recurrences after surgery 3 years ago were accepted surgery again followed by one year without recurrence. One case who recurrence 1 year later was accepted repairing surgery of cerebrospinal fluid leakage used endoscope merge craniotomy and ventricle celiac bypass followed six months without recurrence. One cash after once surgery was followed half a year without recurrence. One case with recurrence 5 years later was accepted repairing surgery again. The patient with empty sella combined cerebrospinal fluid leakage of nasal was rare, the main method was endoscopic sinus surgery treatment, but it recurred usually. The patients with repeatedly recurrence can be considered to accepted the surgery of ventricle celiac bypass. It required long-term postoperative follow-up and review.

  13. Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection.

    PubMed

    Natale, Fabio; Bizzarri, Bianca; Cardi, Veronica; Gaeta, Aurelia; Villani, Paola; Liuzzi, Giuseppina; De Curtis, Mario

    2015-03-31

    Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here, we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection.

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

    PubMed Central

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

    2013-01-01

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

  15. 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.

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

    PubMed

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

    2014-04-01

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

  17. Duloxetine enters the brain - But why is it not found in the cerebrospinal fluid.

    PubMed

    Paulzen, Michael; Gründer, Gerhard; Veselinovic, Tanja; Wolf, Bernhard; Hiemke, Christoph; Lammertz, Sarah E

    2016-01-01

    Antidepressants enter the brain to reach their site of action in a different extent. However, there has been no study to date about duloxetine's ability to enter the brain and cerebrospinal fluid. Aim of this study was to measure blood and cerebrospinal fluid concentrations of duloxetine and to account for the distribution between the two compartments. Concentrations of duloxetine were measured in blood serum and cerebrospinal fluid of 19 patients treated with daily doses of 30-120mg. Daily doses were correlated with serum and cerebrospinal fluid concentrations and serum concentrations were correlated with concentrations in cerebrospinal fluid. Serum concentrations of duloxetine showed a moderate but significant correlation with the applied daily dose, r=+0.473, p=0.04. Duloxetine concentrations in the cerebrospinal fluid above the designated limit of quantification of 2.0ng/mL were only found in three of the 19 patients. Contrasting to own preceding studies on venlafaxine, mirtazapine and citalopram with comparably high concentrations in cerebrospinal fluid, the here presented findings indicate that duloxetine shows a very different distribution pattern. Very low concentrations in the cerebrospinal fluid may be due to the fact that the drug crosses the blood-cerebrospinal fluid barrier much worse than other antidepressants do, suggesting a low ability of duloxetine to enter the brain. Alternatively, low drug concentrations may be interpreted in a sense of a missing residence time in cerebrospinal fluid due to active transport mechanisms out of this environment either back into the bloodstream or into the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    1989-01-01

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

  1. Thermal effect of dielectrophoresis manipulation on cerebrospinal fluid.

    PubMed

    Miled, Amine

    2014-01-01

    This paper introduces an investigation on the thermal effects of dielectrophoresis on cerebrospinal fluid (CSF). It highlights the temperature propagation in CSF according to applied voltage and generated electrical field in a limited area of the brain. Through the described study, the temperature increase is considerable in the close surrounding area of electrodes where applied voltage goes up to 20 V(rms) in order to generate dielectrophoretic forces for CSF sampling. Matlab simulations detailed in this work are based on the assumption that the propagation of temperature in CSF is linear. The objective of this research is to study the thermal side effects of direct measurements and manipulations of neurotransmitters in the brain versus in-channel measurement of neurotransmitter concentration. Indeed, according to simulation results, if the temperature in the top of electrodes is 46.85 °C then it will decrease only to 45.35 °C at 1 mm away from electrode surface.

  2. 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

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

    PubMed

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

    2002-09-01

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

  4. Cerebrospinal fluid levels of insulin in patients with Alzheimer's disease.

    PubMed

    Molina, J A; Jiménez-Jiménez, F J; Vargas, C; Gómez, P; de Bustos, F; Gómez-Escalonilla, C; Zurdo, M; Tallón, A; Martínez-Salio, A; Porta-Etessam, J; Villanueva, C; Arenas, J

    2002-12-01

    Some previous reports suggested a potential role of insulin in memory and in the pathophysiology of Alzheimer's disease (AD). We assessed the cerebrospinal fluid (CSF) levels of insulin in patients with AD and in age and sex-matched controls trying to elucidate whether this value could be related with the risk or severity of AD. We measured the CSF insulin levels in 27 patients with AD and 16 matched controls using a RadioImmunoanalysis method. CSF insulin levels did not differ significantly between AD-patient and control groups. These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. These results suggest that CSF insulin concentrations are not related with the risk or severity of AD. Copyright Blackwell Munksgaard 2002

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

  8. 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

  9. Sphingomonas Paucimobilis: A Rare Infectious Agent Found in Cerebrospinal Fluid.

    PubMed

    Göker, Tuncer; Aşık, Rahile Zülal; Yılmaz, Muhammet Bahadır; Çelik, İlhami; Tekiner, Ayhan

    2017-07-01

    Sphingomonas paucimobilis (S. paucimobilis) is a gram negative bacillus. It has existed in soil, drinking water and plants. It has been isolated from distilled water tanks, respirators, and hemodialysis devices at the hospital setting. Patients with chronic disorders or immune suppression may be susceptible to infections with it. This microorganism has also been reported to infect healthy persons. Both nosocomial and community-acquired infections have been reported. So far, a variety of infections have been reported, including sepsis, septic pulmonary embolism, septic arthritis, peritonitis, and endophthalmitis. Only 2 cases of meningitis have been reported so far in the literature. So far, no previous reports of culture proliferation have been reported in patients with external ventricular drains, as was the case in our patient. Therefore, our case is the first to have S. paucimobilis proliferation in cerebrospinal fluid culture during intensive care unit stay for an external ventricular drain.

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

    PubMed Central

    Zappaterra, Mauro W.; Lehtinen, Maria K.

    2013-01-01

    The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury. PMID:22415326

  11. Cerebrospinal fluid otorrhea through a congenitally patent fallopian canal.

    PubMed

    Foyt, D; Brackmann, D E

    2000-04-01

    Cerebrospinal fluid (CSF) otorrhea is a relatively rare entity that may occur either as a spontaneous occurrence or as a result of trauma or surgery. Spontaneous CSF leaks may be found during tympanocentesis, myringotomy, or tube insertion for chronic middle ear effusion. Rapid identification of the problem and timely treatment are required to avoid life-threatening complications such as meningitis. The site of leakage must also be identified so that the disorder can be treated effectively. Computed tomography, magnetic resonance imaging, and radionucleotide localization scanning all play a role in the early identification of the leakage site. A detailed knowledge of possible CSF leakage pathways aids in evaluating imaging studies. We report 2 rare cases of CSF otorrhea through a congenitally patent facial canal and their management.

  12. Massive Cerebrospinal Fluid Leak of the Temporal Bone

    PubMed Central

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

    2016-01-01

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

  13. Massive Cerebrospinal Fluid Leak of the Temporal Bone.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-10-01

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

  15. Orbital cerebrospinal fluid accumulation after complicated pterional-orbitozygomatic craniotomy.

    PubMed

    Yoon, Michael K; Piluek, Wachirapon Jordan; Ruggiero, Jason P; McDermott, Michael W; McCulley, Timothy J

    2014-12-01

    We describe 2 patients who developed postoperative orbital cerebrospinal fluid (CSF) collection after orbitozygomatic pterional craniotomy. An 18-year-old woman underwent exploratory pterional-orbitozygomatic craniotomy. Five days postoperatively, after removal of a lumbar drain, proptosis and a compressive optic neuropathy developed. Computed tomography demonstrated a CSF collection contiguous with the craniotomy site. Resolution followed percutaneous aspiration and replacement of the lumbar drain. A 57-year-old woman underwent a pterional-orbitozygomatic craniotomy for removal of a left anterior clinoid meningioma, complicated by a large left hemorrhagic stroke requiring decompressive hemicraniectomy. Extracranial CSF collections accumulated in both the orbit and subgaleal spaces. Resolution followed placement of an external ventricular drain. Based on these cases, the mechanism seems to be the combination of iatrogenic formation of a communication with the subarachnoid space and elevated intracranial pressure. Resolution was achieved by normalizing intracranial pressure.

  16. Cerebrospinal fluid galactorrhea: a rare complication of ventriculoperitoneal shunting.

    PubMed

    Lee, Sai-Cheung; Chen, Jyi-Feng; Tu, Po-Hsun; Lee, Shih-Tseng

    2008-06-01

    In this report we describe a 26-year-old woman who had an intra-abdominal pseudocyst located at the peritoneal catheter tip following ventriculo-peritoneal (VP) shunt implantation. Retrograde cerebrospinal fluid (CSF) flowed outside the catheter and communicated with the right breast lactiferous ductal system and leaked from the nipple orifice. CSF galactorrhea only occurs when the lactiferous duct is injured during VP shunt implantation, in combination with the formation of an intra-abdominal CSF pseudocyst prior to lactiferous duct healing. Leakage of CSF from the nipple orifice can be successfully treated by simply guiding the peritoneal catheter tip into the peritoneal cavity through a new laparotomy; that is, shunt revision is not always required.

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

    PubMed Central

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

    2012-01-01

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

  18. Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.

    PubMed

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

    2014-06-25

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

  19. Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

    PubMed

    Vinther-Jensen, T; Simonsen, A H; Budtz-Jørgensen, E; Hjermind, L E; Nielsen, J E

    2015-10-01

    Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers. Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset. © 2015 EAN.

  20. Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease.

    PubMed

    Yang, Yue; Keene, C Dirk; Peskind, Elaine R; Galasko, Douglas R; Hu, Shu-Ching; Cudaback, Eiron; Wilson, Angela M; Li, Ge; Yu, Chang-En; Montine, Kathleen S; Zhang, Jing; Baird, Geoffrey S; Hyman, Bradley T; Montine, Thomas J

    2015-07-01

    Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study was to develop a method to quantify CSF particles and evaluate their relationship to aging and neurodegenerative diseases. We used a flow cytometric assay to detect annexin V-, apoE-, apoAI-, apoJ-, and amyloid (A) β42-positive particles in CSF from 131 research volunteers who were neurologically normal or had mild cognitive impairment (MCI), Alzheimer disease (AD) dementia, or Parkinson disease. APOE ε4/ε4 participants had CSF apoE-positive particles that were more frequently larger but at an 88% lower level versus those in APOE ε3/ε3 or APOE ε3/ε4 patients; this finding was reproduced in conditioned medium from mouse primary glial cell cultures with targeted replacement of apoE. Cerebrospinal fluid apoE-positive and β-amyloid (Aβ42)-positive particle concentrations were persistently reduced one-third to one-half in middle and older age subjects; apoAI-positive particle concentration progressively increased approximately 2-fold with age. Both apoAI-positive and annexin V-positive CSF particle levels were reduced one-third to one-half in CSF of MCI and/or AD dementia patients versus age-matched controls. Our approach provides new methods to investigate CNS lipid biology in relation to neurodegeneration and perhaps develop new biomarkers for diagnosis or treatment monitoring.

  1. 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

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

    PubMed

    Sweetman, Brian; Linninger, Andreas A

    2011-01-01

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

  3. Reversal of Progressive Conscious Disturbance with Epidural Blood Patch for Cerebrospinal Fluid Leakage at C2 Level.

    PubMed

    Lai, Yi-Chen; Chia, Yuan-Yi; Lien, Wei-Hung

    2017-03-01

    Intracranial hypotension syndrome (IHS) is generally caused by cerebrospinal fluid (CSF) leakage. Complications include bilateral subdural hygroma or haematoma and herniation of the cerebellar tonsils. Epidural blood patch (EBP) therapy is indicated if conservative treatment is ineffective. We reported the case of a 46-year-old man with a history of postural headache and dizziness. The patient was treated with bed rest and daily hydration with 2000 mL of fluid for 2 weeks. However, dizziness and headache did not resolve, and he became drowsy and disoriented with incomprehensible speech. Magnetic resonance imaging demonstrated diffuse dural enhancement on the postcontrast study, sagging of the midbrain, and CSF leakage over right lateral posterior thecal sac at C2 level. We performed EBP at the level of T10-T11. We injected 14 mL of autologous blood slowly in the Trendelenburg position. Within 30 minutes, he became alert and oriented to people, place, and time. We chose thoracic EBP as first line treatment in consideration of the risk of cervical EBP such as spinal cord and nerve root compression or puncture, chemical meningitis. Also we put our patient in Trendelenburg position to make blood travel towards the site of the leak. Untreated IHS may delay the course of resolution and affect the patient's consciousness. Delivery of EBP via an epidural catheter inserted from the thoracic spine is familiar with most of anesthesiologists. It can be a safe and effective treatment for patients with IHS caused by CSF leak even at C2.Key words: Anaesthetic techniques, regional, thoracic; cerebrospinal fluid leakage; epidural blood patch; heavily T2-weighted magnetic resonance myelography; intracranial hypotension syndrome; Trendelenburg position.

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

    PubMed

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

    2014-08-28

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

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

    PubMed Central

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

    2014-01-01

    Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications. PMID:25165051

  6. Surgical treatment of cervical disc protrusion causing intracranial hypotension following chiropractic manipulation.

    PubMed

    Wilson, David; Steel, Timothy; Sutton, Ian

    2015-09-01

    We describe a woman with intracranial hypotension provoked by a combination of calcified disc protrusion and chiropractic manipulation who required surgical intervention for definitive treatment. Intracranial hypotension is a rare but increasingly well recognized cause of orthostatic headache that arises due to spinal cerebrospinal fluid leakage from meningeal diverticula or dural perforations.

  7. 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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

    Finley, P R; Williams, R J

    1983-01-01

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

  10. Prehospital management and fluid resuscitation in hypotensive trauma patients admitted to Karolinska University Hospital in Stockholm.

    PubMed

    Talving, Peep; Pålstedt, Joakim; Riddez, Louis

    2005-01-01

    Few previous studies have been conducted on the prehospital management of hypotensive trauma patients in Stockholm County. The aim of this study was to describe the prehospital management of hypotensive trauma patients admitted to the largest trauma center in Sweden, and to assess whether prehospital trauma life support (PHTLS) guidelines have been implemented regarding prehospital time intervals and fluid therapy. In addition, the effects of the age, type of injury, injury severity, prehospital time interval, blood pressure, and fluid therapy on outcome were investigated. This is a retrospective, descriptive study on consecutive, hypotensive trauma patients (systolic blood pressure < or = 90 mmHg on the scene of injury) admitted to Karolinska University Hospital in Stockholm, Sweden, during 2001-2003. The reported values are medians with interquartile ranges. Basic demographics, prehospital time intervals and interventions, injury severity scores (ISS), type and volumes of prehospital fluid resuscitation, and 30-day mortality were abstracted. The effects of the patient's age, gender, prehospital time interval, type of injury, injury severity, on-scene and emergency department blood pressure, and resuscitation fluid volumes on mortality were analyzed using the exact logistic regression model. In 102 (71 male) adult patients (age > or = 15 years) recruited, the median age was 35.5 years (range: 27-55 years) and 77 patients (75%) had suffered blunt injury. The predominant trauma mechanisms were falls between levels (24%) and motor vehicle crashes (22%) with an ISS of 28.5 (range: 16-50). The on-scene time interval was 19 minutes (range: 12-24 minutes). Fluid therapy was initiated at the scene of injury in the majority of patients (73%) regardless of the type of injury (77 blunt [75%] / 25 penetrating [25%]) or injury severity (ISS: 0-20; 21-40; 41-75). Age (odds ratio (OR) = 1.04), male gender (OR = 3.2), ISS 21-40 (OR = 13.6), and ISS >40 (OR = 43.6) were the

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Palmqvist, Sebastian; Mattsson, Niklas; Hansson, Oskar

    2016-04-01

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

  13. Spontaneous bilateral and concurrent cerebrospinal fluid otorrhoea: case presentation and literature review.

    PubMed

    Tikka, T; Opeodu, A; Irving, R; Murphy, J

    2016-08-01

    Cerebrospinal fluid otorrhoea is a rare entity. Only a few cases of spontaneous bilateral cerebrospinal fluid otorrhoea have been reported. In all cases, there was a definite time interval between the two (left and right) presentations. To raise awareness and report on the very rare entity of bilateral spontaneous cerebrospinal fluid otorrhoea. This paper reports the case of a bilateral, synchronous, spontaneous cerebrospinal fluid otorrhoea in a 44-year-old female. The patient had grommets surgically inserted on two separate occasions for treatment of otitis media with effusion, and received several courses of oral and topical antibiotics. Five years following the patient's initial presentation, a suspicion of concurrent bilateral cerebrospinal fluid otorrhoea was raised. The otorrhoea sample collected proved to be cerebrospinal fluid. Cross-sectional imaging revealed bilateral defects in the tegmen tympani of the skull base. She underwent staged middle fossa craniotomies to repair the defects. Careful observation of the middle-ear fluid characteristics following myringotomy can allow for prompt diagnosis.

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

    PubMed

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

    2016-03-01

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

  15. Cerebrospinal fluid biomarkers of simian immunodeficiency virus encephalitis

    PubMed Central

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

    2016-01-01

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

  16. 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.

  17. Florbetapir positron emission tomography and cerebrospinal fluid biomarkers

    PubMed Central

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

    2015-01-01

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

  18. Bioinformatic software for cerebrospinal fluid spectrophotometry in suspected subarachnoid haemorrhage.

    PubMed

    Collet, Nicolas; Garcelon, Nicolas; Robbe, Valentin; Lucas-Clerc, Catherine; Cuggia, Marc; Bendavid, Claude

    2012-03-01

    Diagnosis of subarachnoid haemorrhage (SAH) is firstly based on imaging and secondly on spectrophotometry. Bilirubin may be detected in the cerebrospinal fluid (CSF) for up to two weeks after SAH. CSF pigment analysis is commonly performed according to the Chalmers manual technique but may be prone to operator error. We propose an online software solution, based on the United Kingdom National External Quality Assessment Service (UKNEQAS) recommendations, to support the interpretation of CSF pigment analysis. Based on the manual Chalmers technique, we have developed a web application (in Personal Home Page language including JpGraph module and an Oracle database(®)) that enables the calculation of net oxyhaemoglobin absorbance and net bilirubin absorbance. It uses data from the CSF spectrophotometry, CSF and serum protein concentrations, and serum bilirubin concentration to provide an interpretation based on the NEQAS decision tree. The application was retrospectively validated using the spectra from 350 patients, previously analysed by the manual method. In total, 91.1% interpretations from spectra analysed with the web application were in accordance with the results obtained manually. The 8.9% discordant results were mostly related to an incorrect interpretation using the manual technique. The software developed in our laboratory to interpret CSF pigment analysis results is a precise, robust and useful tool that allows reproducible conclusions to be drawn. This software is available through a web interface.

  19. Free and Total Vitamin B12 in Cerebrospinal Fluid

    PubMed Central

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

    1963-01-01

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

  20. Choroid plexus protects cerebrospinal fluid against toxic metals

    SciTech Connect

    Wei, Zheng; Perry, D.F.; Nelson, D.L.; Aposhian, H.V. )

    1991-05-01

    Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cysteine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.

  1. 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

  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.

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

    PubMed

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

    1991-04-01

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

  4. Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

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

    2011-01-01

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

  5. 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.

  6. 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

  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. Cerebrospinal fluid neopterin and cryopyrin-associated periodic syndrome.

    PubMed

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

    2009-12-01

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

  9. Progranulin Protein Levels in Cerebrospinal Fluid in Primary Neurodegenerative Dementias.

    PubMed

    Morenas-Rodríguez, Estrella; Cervera-Carles, Laura; Vilaplana, Eduard; Alcolea, Daniel; Carmona-Iragui, María; Dols-Icardo, Oriol; Ribosa-Nogué, Roser; Muñoz-Llahuna, Laia; Sala, Isabel; Belén Sánchez-Saudinós, M; Blesa, Rafael; Clarimón, Jordi; Fortea, Juan; Lleó, Alberto

    2016-01-01

    Progranulin is implicated in frontotemporal dementia (FTD), but its role in other neurodegenerative disorders is unknown. To investigate the levels of progranulin (PGRN) in cerebrospinal fluid (CSF) in different neurodegenerative dementias and their correlation with levels in plasma in cognitively normal subjects. We measured PGRN in CSF in 229 patients with amnestic mild cognitive impairment, Alzheimer's disease dementia, sporadic FTD, dementia with Lewy bodies, corticobasal syndrome, or progressive supranuclear palsy. We also measured PGRN in CSF and plasma in 74 cognitively normal individuals. We examined the correlation between PGRN levels in CSF and diagnosis, cortical thickness, genetic factors and other CSF biomarkers. We also investigated the correlation between plasma and CSF levels of PGRN in cognitively normal individuals. CSF levels did not differ across diagnoses or correlate with cortical thickness. Polymorphism rs5848 in GRN influenced CSF PGRN levels, but APOEɛ4 allele did not. Amyloid-β42, t-tau, p-tau, and YKL-40 levels correlated weakly with PGRN in CSF. We found a weak correlation (r = 0.362) between plasma and CSF PGRN levels in cognitively normal individuals. Our findings do not support a diagnostic value of CSF PGRN in neurodegenerative diseases. Our data confirm that levels of PGRN in plasma do not reflect accurately levels in CSF in cognitively normal controls. These data should be considered in clinical trials aiming to increase PGRN.

  10. Endoscopic repair of frontal sinus cerebrospinal fluid leaks.

    PubMed

    Woodworth, B A; Schlosser, R J; Palmer, J N

    2005-09-01

    To describe endoscopic management of frontal sinus cerebrospinal fluid (CSF) leaks. Retrospective. We reviewed all frontal sinus CSF leaks treated using an endoscopic approach at our institutions from 1998 to 2003. CSF leaks originated immediately adjacent to or within the frontal recess or frontal sinus proper for inclusion in the study. Data collected included demographics, presenting signs and symptoms, site and size of skull-base defect, surgical approach, repair technique, and clinical follow up. Seven frontal sinus CSF leaks in six patients were repaired endoscopically. Average age of presentation was 45 years (range 25-65 years). Aetiology was idiopathic (three), congenital (one), accidental trauma (one), and surgical trauma (two). All patients presented with CSF rhinorrhea; two patients presented with meningitis. Four defects originated in the frontal recess, while two others involved the posterior table and frontal sinus outflow tract. Four patients had associated encephaloceles. We performed endoscopic repair in all six patients with one patient requiring an adjuvant osteoplastic flap without obliteration. All repairs were successful at the first attempt with a mean follow up of 13 months. All frontal sinuses remained patent on both post-operative endoscopic and radiographic exam. Endoscopic repair of frontal sinus CSF leaks and encephaloceles can be an effective method if meticulous attention is directed toward preservation of the frontal sinus outflow tract, thus avoiding an osteoplastic flap and obliteration. The major limiting factor for an endoscopic approach is extreme extension superiorly or laterally within the posterior table beyond the reach of current instrumentation.

  11. Fluorescence imaging of lymphatic outflow of cerebrospinal fluid in mice.

    PubMed

    Kwon, Sunkuk; Janssen, Christopher F; Velasquez, Fred Christian; Sevick-Muraca, Eva M

    2017-10-01

    Cerebrospinal fluid (CSF) is known to be reabsorbed by the lymphatic vessels and drain into the lymph nodes (LNs) through peripheral lymphatic vessels. In the peripheral lymphatics, the contractile pumping action of lymphangions mediates lymph drainage; yet it is unknown whether lymphatic vessels draining cranial and spinal CSF show similar function. Herein, we used non-invasive near-infrared fluorescence imaging (NIRFI) to image (i) indocyanine green (ICG) distribution along the neuraxis and (ii) routes of ICG-laden CSF outflow into the lymphatics following intrathecal lumbar administration. We demonstrate lymphatic contractile function in peripheral lymphatics draining from the nasal lymphatics to the mandibular LNs. In addition, we observed afferent sciatic lymphatic vessels, which also show contractile activity and transport spinal CSF into the sciatic LNs. This drainage pattern was also visualized by NIRFI following intrathecal thoracic injection. In situ intravital imaging following intrathecal lumbar injection of blue dye shows similar distributions to that seen in vivo with ICG. NIRFI could be used as a tool to probe CSF pathology including neurological disorders by imaging CSF outflow dynamics to lymphatics. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Hepatic cerebrospinal fluid pseudocyst: A rare complication of ventriculoperitoneal shunt

    PubMed Central

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

    2013-01-01

    Background: Ventriculoperitoneal (VP) shunts are among the most frequently performed operations in the management of hydrocephalus. Hepatic cerebrospinal fluid (CSF) pseudocyst is a rare but important complication in patients with a VP shunt insertion. In addition to presenting our own case, we performed a PubMed search to comprehensively illustrate the predisposing factors, clinical picture, diagnostic methods, and surgical treatment. This article represents an update for this condition. Case Description: A 40-year-old male was admitted to a hospital complaining of fever, abdominal distention, and pain. He had undergone a VP shunt for communicating hydrocephalus caused by a head trauma one year earlier. Laboratory studies showed liver enzymes alterations, and imaging studies demonstrated a well-defined intraaxially hepatic cyst with the shunt catheter placed inside. Staphylococcus epidermis was cultured via CSF. After removing the VP shunt and an adequate antibiotic treatment, the complication of hepatic CSF pseudocyst was resolved. Conclusion: Hepatic CSF pseudocyst is a rare complication of a VP shunt. Once the diagnosis is verified and if the CSF is sterile, just simply remove the peritoneal catheter and reposition a new one in the abdomen. We believe that it is not necessary to remove or aspirate the hepatic intraaxial pseudocyst, because of the risk of bleeding. In case of CSF infection, the VP shunt can be removed and/or an external derivation can be made, and after treatment with antibiotics, a new VP shunt is placed in the opposite side of the peritoneum. PMID:24523999

  13. Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases.

    PubMed

    Lleó, Alberto; Cavedo, Enrica; Parnetti, Lucilla; Vanderstichele, Hugo; Herukka, Sanna Kaisa; Andreasen, Niels; Ghidoni, Roberta; Lewczuk, Piotr; Jeromin, Andreas; Winblad, Bengt; Tsolaki, Magda; Mroczko, Barbara; Visser, Pieter Jelle; Santana, Isabel; Svenningsson, Per; Blennow, Kaj; Aarsland, Dag; Molinuevo, José Luis; Zetterberg, Henrik; Mollenhauer, Brit

    2015-01-01

    Alzheimer disease (AD) and Parkinson disease (PD) are the most common neurodegenerative disorders. For both diseases, early intervention is thought to be essential to the success of disease-modifying treatments. Cerebrospinal fluid (CSF) can reflect some of the pathophysiological changes that occur in the brain, and the number of CSF biomarkers under investigation in neurodegenerative conditions has grown rapidly in the past 20 years. In AD, CSF biomarkers are increasingly being used in clinical practice, and have been incorporated into the majority of clinical trials to demonstrate target engagement, to enrich or stratify patient groups, and to find evidence of disease modification. In PD, CSF biomarkers have not yet reached the clinic, but are being studied in patients with parkinsonism, and are being used in clinical trials either to monitor progression or to demonstrate target engagement and downstream effects of drugs. CSF biomarkers might also serve as surrogate markers of clinical benefit after a specific therapeutic intervention, although additional data are required. It is anticipated that CSF biomarkers will have an important role in trials aimed at disease modification in the near future. In this Review, we provide an overview of CSF biomarkers in AD and PD, and discuss their role in clinical trials.

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

    PubMed

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

    2014-12-01

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

  15. Subtotal Petrosectomy and Cerebrospinal Fluid Leakage in Unilateral Anacusis

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Ferreira, Alexandra

    2016-01-01

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

  17. Cerebrospinal fluid shunt operations without cranial bandaging. Clinical article.

    PubMed

    Winston, Ken R; Trinidad, Elizabeth; Wilkinson, C Corbett; McBride, Lori A

    2009-06-01

    Cranial bandages are commonly applied over scalp incisions immediately after cerebrospinal fluid (CSF) shunt surgery, putatively to prevent complications, particularly infection. These bandages require resources, consume the time of healthcare workers, and incur non-negligible expenses. It is therefore both reasonable and important to examine the efficacy of cranial bandaging. The combined experience of 3 neurosurgeons over 6.75 years with using no cranial bandaging after operations for implantation or revision of CSF shunts is the basis of this report. These data were prospectively accrued and retrospectively analyzed. The infection rate was 4.2% (95% CI 3.1-5.6%) for 1064 operations performed without postoperative cranial bandaging after either shunt insertion or revision surgery through clean or clean-contaminated wounds. The age distribution extended from premature infants through adults 77 years of age. The results of this investigation support the position that bandaging scalp wounds after CSF shunt implantation or revision surgery adds no benefit beyond the easier, simpler, faster, and cheaper practice of using antibiotic ointment as a dressing without bandaging.

  18. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.

    PubMed

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

    2010-03-01

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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. Oscillations of cerebrospinal fluid pressure in nonhydrocephalic persons.

    PubMed

    Droste, D W; Krauss, J K

    1997-04-01

    Spontaneous cerebrospinal fluid (CSF) pressure oscillations with a wavelength of 0.5-2/min (B-waves) are used as a criterion for shunt insertion in hydrocephalic patients. We describe CSF pressure oscillations in two nonhydrocephalic patients with normal baseline CSF pressure. Intracranial pressure was recorded via a ventricular drainage in a 54-year-old male who had a lumber CSF leak after surgery for lumbar spinal stenosis and disc herniation after the leak was closed. In the second patient, a 42-year-old male, CSF pressure was monitored via a lumbar drainage which was placed for treatment of a subcutaneous CSF effusion after resection of a recurrent temporal meningioma. CSF pressure oscillations of a wavelength of 0.5-2/min were observed with a relative frequency of 50% (patient 1) and 60% (patient 2) of the recorded time. Also longer waves were observed. Our data suggest that CSF pressure oscillations are not confined to hydrocephalic patients with raised intracranial pressure.

  2. Nimodipine transfer into human breast milk and cerebrospinal fluid.

    PubMed

    Carcas, A J; Abad-Santos, F; de Rosendo, J M; Frias, J

    1996-02-01

    To report nimodipine concentrations in breast milk and cerebrospinal fluid (CSF) of a lactating woman who was given the drug to prevent a vascular spasm secondary to angiographic examination. A 36-year-old woman received a total dose of nimodipine 46 mg iv over 24 hours. She extracted milk when she noted mammary tightness, and blood samples were taken simultaneously by venipuncture in the arm contralateral to that of the nimodipine infusion. A CSF sample also was taken in a diagnostic lumbar puncture. Nimodipine concentration in milk was much lower than that in serum, with a milk/serum ratio of 0.06-0.15. The CSF/serum ratio was 0.01. We estimate that the infant would have received between 0.008% and 0.092% of the weight-adjusted dose that was administered to the mother if the baby had been nursed. Nimodipine is transferred to human milk in a lower proportion than are other calcium-channel blockers. These results suggest that treating the mother with nimodipine would entail no risk to the nursing infant.

  3. Cerebrospinal fluid ascorbic acid levels in neurological disorders.

    PubMed

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

    1984-02-01

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

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis.

    PubMed

    Verbeek, M M; Notting, E A; Faas, B; Claessens-Linskens, R; Jongen, P J H

    2010-05-01

    To investigate chitotriosidase (CTTS) activity in serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients in relation to disease course and CSF markers for immune activation or inflammation. We studied 80 patients with relapsing-remitting MS (RRMS), 24 with secondary progressive MS (SPMS), 20 with primary progressive MS (PPMS) and 29 patients with other neurological disorders (OND). We measured CTTS activity and studied the correlation with CSF mononuclear cell count (MNC) and intrathecal IgG production. CTTS activity was significantly higher in CSF, but not in serum, from the total MS group compared with OND and controls. In RRMS and SPMS CTTS, index was increased compared with controls (RRMS, 0.10 +/- 0.21; SPMS, 0.10 +/- 0.15; controls, 0.021 +/- 0.020), but not in PPMS (0.061 +/- 0.052). CTTS index was higher in MS patients with elevated MNC or CSF-restricted oligoclonal IgG bands than in MS patients without these CSF findings. CTTS index is elevated in RRMS and SPMS. The CTTS index is related to CSF markers of inflammation or immune activation.

  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.

  7. 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

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

    PubMed

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

    2017-01-01

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

  9. Diagnosis of lymphomatous leptomeningitis by cerebrospinal fluid lymphocyte cell surface markers.

    PubMed

    Goodson, J D; Strauss, G M

    1979-06-01

    We present a patient with metastatic lymphomatous leptomeningitis in whom the diagnosis was made on the basis of cerebrospinal fluid lymphocyte surface markers and later confirmed by cerebrospinal fluid cytology. The diagnosis of metastatic leptomeningitis can be elusive, and the differential includes a wide variety of infectious and noninfectious processes. We propose that lymphocyte surface marker studies can be a useful technique in expediting the evaluation of certain patients with lymphoma who have evidence of central nervous sytem involvement.

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

    PubMed

    van den Doel, E M

    1987-12-01

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

  11. 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.

  12. Choroidal Proteins Involved in Cerebrospinal Fluid Production may be Potential Drug Targets for Alzheimer's Disease Therapy.

    PubMed

    Wostyn, Peter; Audenaert, Kurt; De Deyn, Peter Paul

    2011-02-23

    Alzheimer's disease is known to be the most common form of dementia in the elderly. It is clinically characterized by impairment of cognitive functions, as well as changes in personality, behavioral disturbances and an impaired ability to perform activities of daily living. To date, there are no effective ways to cure or reverse the disease. Genetic studies of early-onset familial Alzheimer's disease cases revealed causative mutations in the genes encoding β-amyloid precursor protein and the γ-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of β-amyloid in the pathogenesis of Alzheimer's disease. Compromised function of the choroid plexus and defective cerebrospinal fluid production and turnover, with diminished clearance of β-amyloid, may play an important role in late-onset forms of Alzheimer's disease. If reduced cerebrospinal fluid turnover is a risk factor for Alzheimer's disease, then therapeutic strategies to improve cerebrospinal fluid flow are reasonable. However, the role of deficient cerebrospinal fluid dynamics in Alzheimer's disease and the relevance of choroidal proteins as potential therapeutic targets to enhance cerebrospinal fluid turnover have received relatively little research attention. In this paper, we discuss several choroidal proteins, such as Na(+)-K(+) ATPase, carbonic anhydrase, and aquaporin 1, that may be targets for pharmacological up-regulation of cerebrospinal fluid formation. The search for potentially beneficial drugs useful to ameliorate Alzheimer's disease by facilitating cerebrospinal fluid production and turnover may be an important area for future research. However, the ultimate utility of such modulators in the management of Alzheimer's disease remains to be determined. Here, we hypothesize that caffeine, the most commonly used psychoactive drug in the world, may be an attractive therapeutic candidate for treatment of Alzheimer's disease since long-term caffeine consumption may

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

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

    2017-01-01

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

  15. Metabolite profile of cerebrospinal fluid in patients with spina bifida: a proton magnetic resonance spectroscopy study.

    PubMed

    Pal, Kamalesh; Sharma, Uma; Gupta, D K; Pratap, Akshay; Jagannathan, N R

    2005-02-01

    The present study was carried out to assess the metabolic differences between cerebrospinal fluid samples of patients with spina bifida and age-matched control individuals. To study the metabolite profile of cerebrospinal fluid of patients with spina bifida using proton magnetic resonance spectroscopy, compare the levels of metabolites with controls, establish correlation of underlying neuronal dysfunction with metabolic changes in patients with spina bifida, and evaluate the potential use of this technique as an additional tool for diagnostic assessment. Combination of embryopathy, stretching, ischemia, compression, and trauma is responsible for cord dysfunction in spina bifida. Changes in neuronal metabolism leads to changes in the local milieu of cerebrospinal fluid in the cord. Change in metabolite profile of cerebrospinal fluid in spina bifida in terms of increase in products of anaerobic metabolism, nerve membrane integrity, and nerve ischemia has not yet been studied. Cerebrospinal fluid obtained from patients and control individuals were characterized using various one- and two-dimensional proton magnetic resonance spectroscopy techniques. Concentration of various metabolites was calculated using the area under the nuclear magnetic resonance peak. Statistically significantly higher levels of lactate, choline, glycerophosphocholine, acetate, and alanine in the cerebrospinal fluid of patients with spina bifida was observed compared with control individuals. Significantly higher levels of metabolites were observed in patients with spina bifida, representing a state of nerve ischemia, anaerobic metabolism, and disruption of neuronal membrane.

  16. Prehospital fluid resuscitation in hypotensive trauma patients: do we need a tailored approach?

    PubMed

    Geeraedts, Leo M G; Pothof, Leonie A H; Caldwell, Erica; de Lange-de Klerk, Elly S M; D'Amours, Scott K

    2015-01-01

    The ideal strategy for prehospital intravenous fluid resuscitation in trauma remains unclear. Fluid resuscitation may reverse shock but aggravate bleeding by raising blood pressure and haemodilution. We examined the effect of prehospital i.v. fluid on the physiologic status and need for blood transfusion in hypotensive trauma patients after their arrival in the emergency department (ED). Retrospective analysis of trauma patients (n=941) with field hypotension presenting to a level 1 trauma centre. Regression models were used to investigate associations between prehospital fluid volumes and shock index and blood transfusion respectively in the emergency department and mortality at 24h. A 1L increase of prehospital i.v. fluid was associated with a 7% decrease of shock index in the emergency department (p<0.001). Volumes of 0.5-1L and 1-2L were associated with reduced likelihood of shock as compared to volumes of 0-0.5L: OR 0.61 (p=0.03) and OR 0.54 (p=0.02), respectively. Volumes of 1-2L were also associated with an increased likelihood of receiving blood transfusion in ED: OR 3.27 (p<0.001). Patients who had received volumes of >2L have a much greater likelihood of receiving blood transfusion in ED: OR 9.92 (p<0.001). Mortality at 24h was not associated with prehospital i.v. fluids. In hypotensive trauma patients, prehospital i.v. fluids were associated with a reduction of likelihood of shock upon arrival in ED. However, volumes of >1L were associated with a markedly increased likelihood of receiving blood transfusion in ED. Therefore, decision making regarding prehospital i.v. fluid resuscitation is critical and may need to be tailored to the individual situation. Further research is needed to clarify whether a causal relationship exists between prehospital i.v. fluid volume and blood transfusion. Also, prospective trials on prehospital i.v. fluid resuscitation strategies in specific patient subgroups (e.g. traumatic brain injury and concomitant haemorrhage) are

  17. The cerebrospinal fluid in multiple sclerosis: far beyond the bands.

    PubMed

    Domingues, Renan Barros; Fernandes, Gustavo Bruniera Peres; Leite, Fernando Brunale Vilela de Moura; Tilbery, Charles Peter; Thomaz, Rodrigo Barbosa; Silva, Gisele Sampaio; Mangueira, Cristóvão Luis Pitangueira; Soares, Carlos Augusto Senne

    2017-01-01

    The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions. RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos

  18. 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

  19. Alterations in Cerebrospinal Fluid in Patients with Bipolar Syndromes

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1983-08-01

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

  1. 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

  2. Physician accountability in iatrogenic cerebrospinal fluid leak litigation.

    PubMed

    Kovalerchik, Olga; Mady, Leila J; Svider, Peter F; Mauro, Andrew C; Baredes, Soly; Liu, James K; Eloy, Jean Anderson

    2013-09-01

    The potentially severe complications resulting from cerebrospinal fluid (CSF) leak makes iatrogenic injury a medicolegal area of concern for otolaryngologists and neurosurgeons. The objectives of this analysis were to study legal outcomes as well as medical and nonmedical elements affecting malpractice litigation. Public court records available in the Westlaw legal database (Thomson Reuters, New York, NY) were searched for medical malpractice litigation related to iatrogenic CSF leak. Of the 18 jury verdicts and settlements included, outcomes and awards, patient demographic data, and other factors instrumental in determining legal responsibility were recorded for comparison. Ten (55.6%) cases were resolved in the defendant's favor, 2 (11.1%) resulted in damages awarded by a jury, and 6 (33.3%) were settled out of court before resolution of trial. Mean damages awarded were $1.1 million, while out of court settlements averaged $966,887. Malpractice stemming from patients who underwent endoscopic sinus surgery comprised 77.8% of cases analyzed. The most frequent alleged factors cited for litigation included having to undergo additional surgery (88.9%), developing meningitis (50.0%), and failing to recognize complications in a timely manner (44.4%). Perceived deficits in informed consent were alleged in one-third of cases. Although a slight majority of cases were resolved in the defendant's favor, payments made were considerable, averaging approximately $1 million. Strategies to decrease liability and allow patients to make more informed decisions should include clear communication with patients that explicitly states potential risks, such as meningitis, and possible need to undergo additional reparative surgery. © 2013 ARS-AAOA, LLC.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. [Management of cerebrospinal fluid leaks according to size. Our experience].

    PubMed

    Alobid, Isam; Enseñat, Joaquim; Rioja, Elena; Enriquez, Karla; Viscovich, Liza; de Notaris, Matteo; Bernal-Sprekelsen, Manuel

    2014-01-01

    We present our experience in the reconstruction of cerebrospinal fluid (CSF) leaks according to their size and location. Fifty-four patients who underwent advanced skull base surgery (large defects) and 62 patients with CSF leaks of different origin (small and medium-sized defects) were included. Large defects were reconstructed with a nasoseptal pedicled flap positioned on fat and fascia lata and lumbar drainage was used. In small and medium-sized leaks of other origin, intrathecal fluorescein 5% was applied previously to identify the defect. Fascia lata in an underlay position was used for reconstruction, which was then covered with mucoperiosteum from the turbinate. Perioperative antibiotics were administered for 5-7 days. Nasal packing was removed after 24-48 hours. The most frequent aetiology for small and medium-sized defects was spontaneous (48.4%), followed by trauma (24.2%), iatrogenic (5%) and others. The success rate was of 91% after the first surgery and 98% in large skull base defects and small/medium-sized respectively. After rescue surgery, the rate of closure achieved was 100%. The follow-up was 15.6 ± 12.4 months for large defects and 75.3 ± 51.3 months for small/medium-sized defects without recurrence. Endoscopic surgery for closure of any type of skull base defect is the gold standard approach. Defect size does not play a significant role in the success rate. Fascia lata and mucoperiosteum allow a reconstruction of small/medium-sized defects. For larger skull base defects, a combination of fat, fascia lata and nasoseptal pedicled flaps provide a successful reconstruction. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy.

    PubMed

    Yilmaz, Aylin; Yiannoutsos, Constantin T; Fuchs, Dietmar; Price, Richard W; Crozier, Kathryn; Hagberg, Lars; Spudich, Serena; Gisslén, Magnus

    2013-05-10

    Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.

  7. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

    PubMed Central

    2013-01-01

    Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008

  8. Cerebrospinal Fluid Aβ to Tau Ratio and Postoperative Cognitive Change

    PubMed Central

    Xie, Zhongcong; McAuliffe, Sayre; Swain, Celeste A.; Ward, Sarah A. P.; Crosby, Catherine A.; Zheng, Hui; Sherman, Janet; Dong, Yuanlin; Zhang, Yiying; Sunder, Neelakantan; Burke, Dennis; Washicosky, Kevin J.; Tanzi, Rudolph E.; Marcantonio, Edward R.

    2013-01-01

    Objective Determination of biomarker and neuropathogenesis of postoperative cognitive change (POCC) or postoperative cognitive dysfunction. Background POCC is one of the most common postoperative complications in elderly patients. Whether preoperative cerebrospinal fluid (CSF) β-amyloid protein (Aβ) to tau ratio, an Alzheimer disease biomarker, is a biomarker for risk of POCC remains unknown. We therefore set out to assess the association between preoperative CSF Aβ42 or Aβ40 to tau ratio and POCC. Methods Patients who had total hip/knee replacement were enrolled. The CSF was obtained during the administration of spinal anesthesia. Cognitive tests were performed with these participants at 1 week before and at 1 week and 3 to 6 months after the surgery. Z scores of the changes from preoperative to postoperative on several key domains of the cognitive battery were determined. We then examined the association between preoperative CSF Aβ42/tau or Aβ40/tau ratio and the outcome measures described earlier, adjusting for age and sex. Results Among the 136 participants (mean age = 71 ± 5 years; 55% men), preoperative CSF Aβ42/tau ratio was associated with postoperative Hopkins Verbal Learning Test Retention [Z score 8.351; age, sex-adjusted (adj.) P = 0.003], and the Benton Judgment of Line= Orientation (Z score 1.242; adj. p = 0.007). Aβ40/tau ratio was associated with Brief Visuospatial Memory Test Total Recall (Z score = 1.045; adj. P = 0.044). Conclusions Preoperative CSF Aβ/tau ratio is associated with postoperative changes in specific cognitive domains. The presence of the Alzheimer's disease biomarker, specifically the Aβ/tau ratio, may identify patients at higher risk for cognitive changes after surgery. PMID:23732272

  9. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis.

    PubMed

    Komori, Mika; Blake, Andrew; Greenwood, Mark; Lin, Yen Chih; Kosa, Peter; Ghazali, Danish; Winokur, Paige; Natrajan, Muktha; Wuest, Simone C; Romm, Elena; Panackal, Anil A; Williamson, Peter R; Wu, Tianxia; Bielekova, Bibiana

    2015-07-01

    The management of complex patients with neuroimmunological diseases is hindered by an inability to reliably measure intrathecal inflammation. Currently implemented laboratory tests developed >40 years ago either are not dynamic or fail to capture low levels of central nervous system (CNS) inflammation. Therefore, we aimed to identify and validate biomarkers of CNS inflammation in 2 blinded, prospectively acquired cohorts of untreated patients with neuroimmunological diseases and embedded controls, with the ultimate goal of developing clinically useful tools. Because biomarkers with maximum utility reflect immune phenotypes, we included an assessment of cell specificity in purified primary immune cells. Biomarkers were quantified by optimized electrochemiluminescent immunoassays. Among markers with cell-specific secretion, soluble CD27 is a validated biomarker of intrathecal T-cell activation, with an area under the receiver operating characteristic curve of 0.97. Comparing the quantities of cerebrospinal fluid (CSF) immune cells and their respective cell-specific soluble biomarkers (released by CSF cells as well as their counterparts in CNS tissue) provided invaluable information about stationary CNS immune responses, previously attainable via brain biopsy only. Unexpectedly, progressive and relapsing-remitting multiple sclerosis (MS) patients have comparable numbers of activated intrathecal T and B cells, which are preferentially embedded in CNS tissue in the former group. The cell-specific biomarkers of intrathecal inflammation may improve diagnosis and management of neuroimmunological diseases and provide pharmacodynamic markers for future therapeutic developments in patients with intrathecal inflammation that is not captured by imaging, such as in progressive MS. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  10. Cerebrospinal Fluid Biomarker for Alzheimer Disease Predicts Postoperative Cognitive Dysfunction.

    PubMed

    Evered, Lisbeth; Silbert, Brendan; Scott, David A; Ames, David; Maruff, Paul; Blennow, Kaj

    2016-02-01

    Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD. CSF samples were collected from 59 patients 60 yr or older who received combined spinal and general anesthesia for elective total hip replacement. Patients underwent neuropsychological testing preoperatively and at 7 days, 3 months, and 12 months postoperatively. POCD at 3 months and cognitive decline at 12 months were calculated by using the reliable change index. CSF amyloid β1-42 (Aβ1-42), total-tau, phosphorylated-tau, and neurofilament light were assayed with enzyme-linked immunosorbent assay methods. POCD was identified in 5 of 57 patients (8.8%) at 3 months. For Aβ1-42, 11 patients were below the cut-point for AD neuropathology of whom 3 were classified with POCD (27.3%; 95% CI, 6.0 to 61%), whereas of the 46 patients above the cut-point, 2 were classified with POCD (4.3%; 95% CI, 0.5 to 14.8%) (P = 0.01). There was no significant difference in the incidence of POCD in relation to the cut-points for any of the other analytes. Low CSF Aβ1-42 may be a significant predictor of POCD at 3 months. This indicates that patients with AD neuropathology even in the absence of clinically detectable AD symptoms may be susceptible to POCD.

  11. Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease

    PubMed Central

    Yang, Yue; Keene, C. Dirk; Peskind, Elaine R.; Galasko, Douglas R.; Hu, Shu-Ching; Cudaback, Eiron; Wilson, Angela M.; Li, Ge; Yu, Chang-En; Montine, Kathleen S.; Zhang, Jing; Baird, Geoffrey S.; Hyman, Bradley T.; Montine, Thomas J.

    2015-01-01

    Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study was to develop a method to quantify CSF particles and evaluate their relationship to aging and neurodegenerative diseases. We used a flow cytometric assay to detect annexin V-, apoE-, apoAI-, apoJ- and amyloid (A) β42-positive particles in CSF from 131 research volunteers who were neurologically normal or had mild cognitive impairment (MCI), Alzheimer disease (AD) dementia, or Parkinson disease. APOE ε4/ε4 participants had CSF apoE-positive particles that were more frequently larger but at an 88% lower level vs. those in APOE ε3/ε3 or APOE ε3/ε4 patients; this finding was reproduced in conditioned medium from mouse primary glial cell cultures with targeted replacement of apoE. CSF apoE-positive and β-amyloid (Aβ42)-positive particle concentrations were persistently reduced one-third to one-half in middle and older age subjects; apoAI-positive particle concentration progressively increased approximately 2-fold with age. Both apoAI-positive and annexin V-positive CSF particle levels were reduced one-third to one-half in CSF of MCI and/or AD dementia patients vs. age-matched controls. Our approach provides new methods to investigate CNS lipid biology in relation to neurodegeneration and perhaps develop new biomarkers for diagnosis or treatment monitoring. PMID:26083568

  12. Increased cerebrospinal fluid Helicobacter pylori antibody in Alzheimer's disease.

    PubMed

    Kountouras, Jannis; Boziki, Marina; Gavalas, Emmanuel; Zavos, Christos; Deretzi, Georgia; Grigoriadis, Nikolaos; Tsolaki, Magda; Chatzopoulos, Dimitrios; Katsinelos, Panagiotis; Tzilves, Dimitrios; Zabouri, Athina; Michailidou, Ifigenia

    2009-01-01

    Helicobacter pylori (H. pylori) infection may play a role in Alzheimer's disease (AD). A prospective, nonrandomized, comparative study was car- ried out to examine the levels of anti-H. pylori-specific IgG antibodies in the cerebrospinal fluid (CSF) and serum of AD patients, compared with those of age-matched cognitively normal controls. CSF was aspirated from 27 AD patients and 27 age-matched cognitively normal patients with prostate hyperplasia or long-bone fractures necessitating surgery after epidural anesthesia. Serum samples were obtained from AD patients and the day before surgery from controls. CSF and serum anti-H. pylori IgG concentrations were measured by means of an enzyme-linked immunosorbent assay. The mean concentration of anti-H. pylori-specific IgG was significantly greater in (a) the CSF of AD patients (10.53 +/- 12.54 U/mL) than in controls (8.63 +/- 8.01 U/mL, p = 0.047), and (b) the serum of AD patients (30.44 +/- 33.94 U/mL) than in controls (16.24 +/- 5.77 U/mL, p = 0.041). CSF anti-H. pylori IgG antibodies correlated with the degree of severity of the disease. H. pylori-specific IgG antibody levels are significantly increased in CSF and serum of AD; its titer in CSF might reflect the AD severity, thereby supporting a role for this common infection in the pathobiology of the disease.

  13. Hyperventilation and cerebrospinal fluid acidosis caused by topiramate.

    PubMed

    Montcriol, Ambroise; Meaudre, Eric; Kenane, Nadia; Asencio, Yves; Bordes, Julien; Palmier, Bruno

    2008-04-01

    To report a case of hyperventilation caused by topiramate therapy and propose a pathophysiologic mechanism for this disorder. A 52-year-old woman with refractory seizure disorder was admitted to the burn care unit with burns over 10% of her body. Her seizure medications, unchanged and well tolerated for several months, included carbamazepine 1200 mg, lamotrigine 500 mg, phenobarbital 80 mg, and topiramate 150 mg per day. During hospitalization, despite a relatively normal arterial pH, the woman developed persistent hyperventilation, with respiratory rates up to 50 breaths/min. Alkalinization did not reduce the hyperventilation. Thoracic contrast-enhanced computed tomographic scan ruled out pulmonary embolism and persistent pneumonia. Salicylate and biguanide screening were negative; results of repeated thyroid and liver function tests were normal. Cerebral magnetic resonance imaging excluded a cerebral pathology. After cerebrospinal fluid (CSF) analysis showed acidosis (pH 7.14), topiramate was withdrawn and the patient's general condition rapidly improved. Forty-eight hours later, the CSF pH had increased to 7.26. The woman was discharged from the burn care unit on the 42nd hospital day. Hyperchloremic normal anion gap metabolic acidosis, which can lead to hyperventilation, has been reported as an adverse effect of topiramate treatment. However, our patient had respiratory alkalosis. Concurrent etiologies of peripheral hyperventilation were excluded, leaving central neurogenic hyperventilation as the remaining etiology. Such central neurogenic hyperventilation associated with topiramate has previously been reported in intensive care. Our case report demonstrates CSF acidosis. Withdrawing topiramate reduced both CSF acidosis and hyperventilation. The mechanism of topiramate-induced CSF acidosis remains unclear. According to the Naranjo probability scale, the relationship of hyperventilation to administration of topiramate in our patient was probable. Normal doses

  14. An applicable method of drawing cerebrospinal fluid in rats.

    PubMed

    Li, Yan; Zhang, Bo; Liu, Xue-Wei; Liu, Ming; Huang, Shu-Ming

    2016-07-01

    Component analysis of cerebrospinal fluid (CSF) is frequently required to probe the causes and pathologic mechanisms of disease and effective drugs in experimental studies of the central nervous system. Rat and mouse are two kinds of most frequently used animals in experimental studies. Rats are considered to be the most suitable animal for experimental analysis of CSF both on cost and manipulability as mice are too small for drawing CSF. However, drawing CSF from rats is still not easy, which makes many researchers choose bigger animals, such as rabbits. This paper introduced a highly applicable technique of CSF collection from cerebellomedullary cistern (CC) in rats. CSF collection with this technique was performed by direct CC puncture using a collection apparatus with negative pressure. The apparatus consists of a 1ml syringe, a disposable intravenous infusion needle and a clip. The needle was cut and made less sharp than the original one to avoid injury to the brain and spinal cord. We have collected CSF multiple times from each rat with this approach and the collection lasted less than 30s each time on average. The length of the collection needles of the CSF was conformed to the different body sizes (weight) of the rats in the 3 groups. Compared with currently existing methods, this is faster, safer, simpler and repeatable. CSF collection by CC puncture using a negative pressure collection apparatus is fast to operate, safe to the rats, and maximum amount of CSF can be collected. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Cerebrospinal fluid from a dog with neurologic collapse.

    PubMed

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

    2003-01-01

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

  16. 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

  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. 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

  19. 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.

  20. Orthostatic Hypotension (Postural Hypotension)

    MedlinePlus

    ... This condition is more common in older adults. Risk factors The risk factors for orthostatic hypotension include: Age. Orthostatic hypotension is ... a result of orthostatic hypotension can be a risk factor for stroke due to the reduced blood supply ...

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

    PubMed

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

    2017-02-01

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

  2. 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.

  3. Abdominal cerebrospinal fluid pseudocyst: a complication of ventriculoperitoneal shunt in a Brazilian Amazon woman. Case report.

    PubMed

    Sena, F Gonçalves; Sousa, R Maia de; Meguins, L Crociati

    2010-01-01

    Ventriculoperitoneal shunt (VPS) is the most common treatment for hydrocephalus, however it is not free of complications. Abdominal cerebrospinal fluid pseudocyst (ACP) is an uncommon, but potentially life-threatening, complication of VPS. It is characterized by a fluid filled collection of cerebrospinal fluid (CSF) in the peritoneal cavity containing the distal end of the VPS catheter and is surrounded by a wall composed of fibrous tissues without an epithelial lining. We report the case a Brazilian Amazon woman that presented ACP fifteen years after the placement of a VPS. Physicians should be aware of this possible complication once early diagnosis would improve outcome and reduce patient's suffering and distress.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    1965-01-01

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

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

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

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

  7. Decreased levels of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension.

    PubMed

    Doppler, Kathrin; Schütt, Morten; Sommer, Claudia

    2016-12-01

    Idiopathic intracranial hypertension is characterized by increased intracranial pressure. Its pathogenesis is largely unknown. Aquaporins may play a role in the homeostasis of cerebrospinal fluid. We aimed to elucidate the role of aquaporins in idiopathic intracranial hypertension by measuring the level of aquaporin-1 and aquaporin-4 in the cerebrospinal fluid and plasma of 28 patients and 29 controls by enzyme-linked immunosorbent assay. The adipokines leptin and retinol-binding protein 4 were also measured. We found a reduction in aquaporin-4 in the cerebrospinal fluid of patients. Leptin levels were increased in the cerebrospinal fluid and plasma of patients and were correlated with weight, body mass index and body fat. There was no difference between patients and controls in the levels of aquaporin-4 and retinol-binding protein 4. Our data suggest that an imbalance of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension may contribute to the pathogenesis of this disorder. © International Headache Society 2016.

  8. Extracranial outflow of particles solved in cerebrospinal fluid: Fluorescein injection study.

    PubMed

    Akai, Takuya; Hatta, Toshihisa; Shimada, Hiroki; Mizuki, Keiji; Kudo, Nae; Hatta, Taizo; Otani, Hiroki

    2017-10-04

    Cerebrospinal fluid is thought to be mainly absorbed into arachnoid granules in the subarachnoid space and drained into the sagittal sinus. However, some observations such as late outbreak of arachnoid granules in fetus brain and recent cerebrospinal fluid movements study by magnetic resonance images, conflict with this hypothesis. In this study, we investigated the movement of cerebrospinal fluid in fetuses. Several kinds of fluorescent probes with different molecular weights were injected into the lateral ventricle or subarachnoid space in mouse fetuses at a gestational age of 13 days. The movements of the probes were monitored by live imaging under fluorescent microscope. Following intraventricular injection, the probes dispersed into the 3(rd) ventricle and aqueduct immediately, but did not move into the 4(th) ventricle and spinal canal. After injection of low and high molecular weight conjugated probes, both probes dispersed into the brain but only the low molecular weight probe dispersed into the whole body. Following intra-subarachnoid injection, both probes diffused into the spinal canal gradually. Neither probe dispersed into the brain and body. The probe injected into the lateral ventricle moved into the spinal central canal by the fetus head compression, and returned into the aqueduct by its release. We conclude this study as follows; 1) The movement of metabolites in cerebrospinal fluid in the ventricles will be restricted by molecular weight. 2) Cerebrospinal fluid in the ventricle and in the subarachnoid space move differently. 3) Cerebrospinal fluid may not appear to circulate. In the event of high intracranial pressure, the fluid may move into the spinal canal. This article is protected by copyright. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  10. 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

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

    PubMed

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

    2017-01-01

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

  13. Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects

    PubMed Central

    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.

    2015-01-01

    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

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

    PubMed

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

    2017-03-01

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

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

    PubMed

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

    1978-02-01

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

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Cerebrospinal fluid levels of tau and phospho-tau-181 proteins during pregnancy.

    PubMed

    Lederer, Wolfgang; Dominguez, Cristina Alomar; Popovscaia, Marina; Putz, Günther; Humpel, Christian

    2016-10-01

    During pregnancy various interactions occur between structural alterations of the maternal brain and placental metabolism. The aim of the present study was to investigate whether cerebrospinal fluid concentrations of tau and phospho-tau-181 protein vary during normal pregnancy and in women with preeclampsia and HELLP syndrome. We measured cerebrospinal fluid biomarkers, tau and phospho-tau-181 protein levels in 90 pregnant women electively assigned for regional anaesthesia during pregnancy or for cesarean section using enzyme-linked immunosorbent assays. Cerebrospinal fluid concentrations for tau and phospho-tau-181 in 66 women with normal pregnancy were 308.5±117.3pg/mL and 50.5±16.7pg/mL, respectively. Blood pressure, liver function, clotting activity and kidney function were significantly different in eleven women with preeclampsia and HELLP syndrome. The weight of the newly born (p<0.001; HR: 0.998), the weight of the placenta (p=0.018) and concentrations for phospho-tau-181 (p=0.043; HR: 1.211) correlated significantly with the disease. Mean concentrations of cerebrospinal fluid tau and phospho-tau-181 protein during pregnancy were evaluated. Phospho-tau-181 protein concentrations correlated with placental function supporting the hypothesis that altered expression of neuronal factors during pregnancy may affect development of the placenta. Copyright © 2016. Published by Elsevier B.V.

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

    USDA-ARS?s Scientific Manuscript database

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

  1. Spontaneous cerebrospinal fluid leaks in the anterior skull base secondary to idiopathic intracranial hypertension.

    PubMed

    Martínez-Capoccioni, Gabriel; Serramito-García, Ramón; Martín-Bailón, Maria; García-Allut, Alfredo; Martín-Martín, Carlos

    2017-05-01

    Spontaneous cerebrospinal fluid (CSF) leaks represent a clinical entity in which CSF rhinorrhea occurs in the absence of any inciting event. Spontaneous CSF leaks are associated with elevated intracranial pressure (ICP) or have underlying idiopathic intracranial hypertension (IIH). We report a cohort of patients who have undergone nasal endoscopic repair for spontaneous CSF leaks. We review our perioperative complications and the effectiveness of the nasal endoscopic approach to repair spontaneous CSF leaks. Also, we examine the evidence correlating spontaneous CSF leaks and IIH and the role of decreasing ICP in the treatment of nasal spontaneous CSF leaks. A retrospective analysis of patients with nasal spontaneous cerebrospinal fluid leaks was performed. Data on the nature of presentation, patient body mass index, defect location and size, ICP, clinical follow-up, and complications were collected. Thirty-five patients had nasal spontaneous cerebrospinal fluid leaks with evidence of IIH's symptoms. The most common sites were the cribriform plate, the ethmoid roof, and sphenoid lateral pterygoid recess. All patients underwent endonasal endoscopic surgery to repair the defect. Postoperatively, all patients underwent lumbar drainage and acetazolamide therapy. Nasal spontaneous cerebrospinal fluid leaks represent a surgical challenge because of their high recurrence rates. The most important factor for obtaining a successful repair in these patients is reducing their intracranial pressure through nutritional, medical, or surgical means.

  2. Using diffusion MRI for measuring the temperature of cerebrospinal fluid within the lateral ventricles.

    PubMed

    Kozak, L R; Bango, M; Szabo, M; Rudas, G; Vidnyanszky, Z; Nagy, Z

    2010-02-01

    Hypothermia is often induced to reduce brain injury in newborns, following perinatal hypoxic-ischaemic events, and in adults following traumatic brain injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion-weighted MRI, to measure non-invasively the temperature of the cerebrospinal fluid in the lateral ventricles. The well-known temperature dependence of the water diffusion constant was used for the estimation of temperature. We carried out diffusion MRI measurements on a 3T Philips Achieva Scanner involving phantoms (filled with water or artificial cerebrospinal fluid while slowly cooling from 41 to 32 degrees C) and healthy adult volunteers. The estimated temperature of water phantoms followed that measured using a mercury thermometer, but the estimates for artificial cerebrospinal fluid were 1.04 degrees C lower. After correcting for this systematic difference, the estimated temperature within the lateral ventricles of volunteers was 39.9 degrees C. Using diffusion directions less sensitive to cerebrospinal fluid flow, it was 37.7 degrees C, which was in agreement with the literature. Although further improvements are needed, measuring the temperature within the lateral ventricles using diffusion MRI is a viable method that may be useful for clinical applications. We introduced the method, identified sources of error and offered remedies for each.

  3. 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

  4. Using diffusion MRI for measuring the temperature of cerebrospinal fluid within the lateral ventricles

    PubMed Central

    Kozak, LR; Bango, M; Szabo, M; Rudas, G; Vidnyanszky, Z; Nagy, Z

    2010-01-01

    Aim: Hypothermia is often induced to reduce brain injury in newborns, following perinatal hypoxic–ischaemic events, and in adults following traumatic brain injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion-weighted MRI, to measure non-invasively the temperature of the cerebrospinal fluid in the lateral ventricles. Methods: The well-known temperature dependence of the water diffusion constant was used for the estimation of temperature. We carried out diffusion MRI measurements on a 3T Philips Achieva Scanner involving phantoms (filled with water or artificial cerebrospinal fluid while slowly cooling from 41 to 32°C) and healthy adult volunteers. Results: The estimated temperature of water phantoms followed that measured using a mercury thermometer, but the estimates for artificial cerebrospinal fluid were 1.04°C lower. After correcting for this systematic difference, the estimated temperature within the lateral ventricles of volunteers was 39.9°C. Using diffusion directions less sensitive to cerebrospinal fluid flow, it was 37.7°C, which was in agreement with the literature. Conclusion: Although further improvements are needed, measuring the temperature within the lateral ventricles using diffusion MRI is a viable method that may be useful for clinical applications. We introduced the method, identified sources of error and offered remedies for each. PMID:19845565

  5. Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study.

    PubMed

    Silversides, Jonathan A; Pinto, Ruxandra; Kuint, Rottem; Wald, Ron; Hladunewich, Michelle A; Lapinsky, Stephen E; Adhikari, Neill K J

    2014-11-18

    In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT). We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors. In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 μmol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did

  6. 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

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

    PubMed

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

    2010-03-01

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

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

    PubMed Central

    Holmes, Courtney; Sharabi, Yehonatan

    2012-01-01

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

  9. A presedation fluid bolus does not decrease the incidence of propofol-induced hypotension in pediatric patients.

    PubMed

    Jager, Matthew D; Aldag, Jean C; Deshpande, Girish G

    2015-02-01

    Propofol is commonly used in pediatric sedation, which may cause hypotension during induction. Our goal was to determine the effect of a preinduction 20-mL/kg isotonic fluid bolus on propofol-induced hypotension, assess clinical signs of hypoperfusion during hypotension, and evaluate for age-related propofol dosing differences. This prospective, randomized, controlled, nonblinded study was conducted at Children's Hospital of Illinois. Patients were children 6 to 60 months of age who needed sedation for MRI or auditory brainstem-evoked response testing. The treatment group received a preinduction 20-mL/kg isotonic saline bolus before procedure initiation. Patients were continuously monitored via cardiorespiratory monitor with pulse oximetry and end-tidal carbon dioxide measurements. Cardiovascular indices and clinical signs of hypoperfusion were compared between groups, and propofol dosing differences were compared between age groups. One hundred twenty-six patients were randomly assigned to treatment (n=52) or control (n=74) conditions. Twelve patients in the treatment group and 14 patients in the control group experienced postinduction hypotension, as defined by the Pediatric Advanced Life Support guidelines. One patient in each group was given volume resuscitation when blood pressure did not improve after a reduction in the propofol infusion rate. No hypotensive patients had physical signs of hypoperfusion, and patients≤1 year of age needed significantly more propofol. A 20-mL/kg preinduction isotonic saline bolus does not prevent propofol-induced hypotension. No clinical signs of hypoperfusion were noted with induced hypotension, and infants≤12 months old need significantly more propofol per kilogram for procedures. Copyright © 2015 by the American Academy of Pediatrics.

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

    PubMed Central

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

    2012-01-01

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

  11. Cerebrospinal fluid testing for the diagnosis of central nervous system infection.

    PubMed

    Zunt, J R; Marra, C M

    1999-11-01

    The central nervous system (CNS) is susceptible to bacterial, viral, and fungal infections, and prion diseases. Examination of the cerebrospinal fluid (CSF) is crucial in diagnosing these infections. Cerebrospinal tests may directly identify an organism and its nucleic acid and surface constituents by culture, polymerase chain reaction (PCR), or antigen detection. Alternatively, antibody to an organism may be identified in CSF by enzyme-linked immunosorbent assay (ELISA), Western blot, or complement fixation assay. This article discusses how these CSF tests are performed and addresses the sensitivity and specificity of such tests for the diagnosis of selected CNS infections.

  12. Morphological characterization of cardiac induced intracranial pressure (ICP) waves in patients with overdrainage of cerebrospinal fluid and negative ICP.

    PubMed

    Eide, Per Kristian; Sroka, Marek; Wozniak, Aleksandra; Sæhle, Terje

    2012-10-01

    Symptomatic overdrainage of cerebrospinal fluid (CSF) can be seen in shunted hydrocephalus patients and in non-shunted patients with spontaneous intracranial hypotension (SIH). In these patients, intracranial pressure (ICP) monitoring often reveals negative static ICP, while it is less understood how the pulsatile ICP (cardiac induced ICP waves) is affected. This latter aspect is addressed in the present study. A set of 40 ICP recordings from paediatric and adult hydrocephalus patients were randomly selected. Each cardiac induced ICP wave was automatically identified and manually verified by the beginning and ending diastolic minimum pressures and the systolic maximum pressure. The ICP wave parameters (static pressure, amplitude, rise time, rise time coefficient, downward coefficient, wave duration, and area-under-curve) were then automatically computed. The material of 40 ICP recordings provided a total of 3,192,166 cardiac induced ICP waves (1,292,522 in paediatric patients and 1,899,644 in adult patients). No apparent changes in ICP wave parameters were seen when mean ICP became negative, except that the parameters amplitude, rise time coefficient, downward coefficient and area under curve somewhat increased when mean ICP was below -15 mmHg.

  13. Cerebrospinal fluid leak after acoustic neuroma surgery: a comparison of the translabyrinthine, middle fossa, and retrosigmoid approaches.

    PubMed

    Becker, Samuel S; Jackler, Robert K; Pitts, Lawrence H

    2003-01-01

    To determine whether the choice of surgical approach affects the rate of postoperative cerebrospinal fluid leakage in patients who have undergone surgical resection of acoustic neuroma. Retrospective chart review. Tertiary referral center. Three hundred patients who underwent surgery for acoustic neuromas were selected by consecutive medical record number until 100 resections via each surgical approach (translabyrinthine, middle fossa, and retrosigmoid) had been gathered. Surgical approach used, cerebrospinal fluid leak incidence, tumor size, patient age. Postoperative cerebrospinal fluid leak of any severity was observed in 13% of translabyrinthine, 10% of middle fossa, and 10% of retrosigmoid patients. These difference in the rate of cerebrospinal fluid leakage were not statistically significant (p = 0.82). The majority of leaks were managed conservatively with fluid and activity restriction, often accompanied by a period of lumbar subarachnoid drainage. There was a need to return to the operating room for a definitive procedure in 4% of translabyrinthine, 2% of middle fossa, and 3% retrosigmoid patients; again not statistically different among the approaches (p = 0.43). Tumor size was not correlated with cerebrospinal fluid leak rate (p = 0.13). Patient age, for patients older than 50 years, was suggestive of increased odds of cerebrospinal fluid leak (p = 0.06). Neither surgical approach nor tumor size affects the rate of postoperative cerebrospinal fluid leakage or the necessity of managing a leak with a return to the operating room. Cerebrospinal fluid leakage rates have remained stable in recent decades despite numerous innovative attempts to improve dural closure, seal transected air cell tracts, and occlude anatomic pathways. The finding that leak rates were similar among three dissimilar surgical techniques suggests that factors other than techniques of wound closure, such as transient postoperative rises in cerebrospinal fluid pressure, may be

  14. Albumin heterogeneity in low-abundance fluids. The case of urine and cerebro-spinal fluid.

    PubMed

    Bruschi, Maurizio; Santucci, Laura; Candiano, Giovanni; Ghiggeri, Gian Marco

    2013-12-01

    Serum albumin is a micro-heterogeneous protein composed of at least 40 isoforms. Its heterogeneity is even more pronounced in biological fluids other than serum, the major being urine and cerebrospinal fluid. Modification 'in situ' and/or selectivity of biological barriers, such as in the kidney, determines the final composition of albumin and may help in definition of inflammatory states. This review focuses on various aspects of albumin heterogeneity in low 'abundance fluids' and highlights the potential source of information in diseases. The electrical charge of the protein in urine and CSF is modified but with an opposite change and depending on clinical conditions. In normal urine, the bulk of albumin is more anionic than in serum for the presence of ten times more fatty acids that introduce equivalent anionic charges and modify hydrophobicity of the protein. At the same time, urinary albumin is more glycosylated compared to the serum homolog. Finally, albumin fragments can be detected in urine in patients with proteinuria. For albumin in CSF, we lack information relative to normal conditions since ethical problems do not allow normal CSF to be studied. In multiple sclerosis, the albumin charge in CSF is more cationic than in serum, this change possibly involving structural anomalies or small molecules bindings. Massively fatty albumin could be toxic for tubular cells and be eliminated on this basis. Renal handling of glycosylated albumin can alter the normal equilibrium of filtration/reabsorption and trigger mechanisms leading to glomerulosclerosis and tubulo-interstitial fibrosis. This article is part of a Special Issue entitled Serum Albumin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  15. 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.

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    1993-10-01

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

  18. Cerebrospinal fluid levels of thiamine in patients with Parkinson's disease.

    PubMed

    Jiménez-Jiménez, F J; Molina, J A; Hernánz, A; Fernández-Vivancos, E; de Bustos, F; Barcenilla, B; Gómez-Escalonilla, C; Zurdo, M; Berbel, A; Villanueva, C

    1999-08-13

    Thiamine is an essential cofactor for several important enzymes involved in brain oxidative metabolism, such as the alpha-ketoglutarate dehydrogenase complex (KGDHC), pyruvate-dehydrogenase complex, and transketolase. The activity of KGDHC is decreased in the substantia nigra or patients with Parkinson's disease (PD). We measured cerebrospinal (CSF) levels of thiamine-diphosphate, thiamine-monophosphate, free thiamine, and total thiamine, using ion-pair reversed phase high performance liquid chromatography, in 24 PD patients and 40 matched controls. The mean CSF levels of thiamine-derivatives did not differ significantly from those of controls, with the exception of lower CSF free thiamine levels in the PD-patient group. PD patients under levodopa therapy had significantly higher CSF thiaminediphosphate and total thiamine than those not treated with this drug. CSF thiamine levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. These results suggest that low CSF free thiamine levels could be related with the risk for PD.

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    2013-01-01

    We present a case of a 49-year old man who suffered from immediate paraplegia upon awakening from anaesthesia after surgery for acute aortic dissection Type A. A catheter was promptly inserted into the spinal canal for cerebrospinal fluid drainage, and the cerebrospinal fluid pressure was maintained <10 cmH2O. Although magnetic resonance imaging showed extensive spinal cord ischaemia, the patient gradually recovered from the paraplegia and was able to walk by himself after rehabilitation. In some cases, cerebrospinal fluid drainage can be effective for the treatment of immediate postoperative spinal cord damage. PMID:24014618

  1. 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

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

    PubMed

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

    2015-08-01

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

  3. 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

  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. Increased selenoprotein P in choroid plexus and cerebrospinal fluid in Alzheimer's disease brain.

    PubMed

    Rueli, Rachel H L H; Parubrub, Arlene C; Dewing, Andrea S T; Hashimoto, Ann C; Bellinger, Miyoko T; Weeber, Edwin J; Uyehara-Lock, Jane H; White, Lon R; Berry, Marla J; Bellinger, Frederick P

    2015-01-01

    Subjects with Alzheimer's disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium.

  6. Intraoperative seizure and cerebrospinal fluid leak during adult cochlear implant surgery.

    PubMed

    Musser, Alexander B; Golub, Justin S; Samy, Ravi N; Phero, James C

    2016-01-01

    To report a rare case of cerebrospinal fluid gusher and subsequent seizure immediately after cochlear implant electrode insertion. After the cochlear implant electrode was inserted, brisk flow of 10 mL of cerebrospinal fluid was seen. The electrode was promptly inserted and the leak was additionally sealed with fascia. Seconds later, the patient had a tonic-clonic seizure lasting 30 seconds. Two additional episodes occurred during the case. Her postoperative course was uneventful with no subsequent seizures. The device has been successfully activated. Intervention & Technique: Postoperative imaging showed correct intracochlear placement of the electrode as well as an incidental enlarged vestibular aqueduct. Neurology consultation including electroencephalogram was unremarkable. To our knowledge, this is the first report of a seizure temporally associated with cochlear implant electrode insertion. The significance and possible casual relationship between these two events is discussed.

  7. Proteomic Biomarker Identification in Cerebrospinal Fluid for Leptomeningeal Metastases with Neurological Complications.

    PubMed

    Galicia, Norma; Díez, Paula; Dégano, Rosa M; Guest, Paul C; Ibarrola, Nieves; Fuentes, Manuel

    2017-01-01

    Leptomeningeal metastases (LM) from solid tumours, lymphoma and leukaemia are characterized by multifocal neurological deficits with a high mortality rate. Early diagnosis and initiation of treatment are essential to kerb neurological deterioration. However, this is not always possible as 25% of cerebrospinal fluid samples produce false-negative results at first cytological examination. The identification of biomarkers that allow stratification of individuals according to risk for developing LM would be a major benefit. Proteomic-based approaches are now in increasing use for this purpose, and these are reviewed in this chapter with a focus on cerebrospinal fluid (CSF) analyses. The construction of a CSF proteome disease database would also facilitate analysis of other neurological disorders.

  8. Occurrence and surgical management of a cerebrospinal fluid-filled cystoid space following routine enucleation.

    PubMed

    Elmalem, Valerie I; Harris, Gerald J

    2012-01-01

    A 73-year-old woman underwent routine enucleation for a blind, painful eye related to end-stage diabetic retinopathy and neovascular glaucoma. A large cystoid space, in continuity with the optic nerve stump, formed around the implant in the first few weeks following surgery. Aspirated contents were positive for β-2 transferrin, confirming cerebrospinal fluid origin. Multiple comorbidities delayed surgical intervention, but the condition was ultimately managed with exposure of the patent optic nerve sheath at the compartment's base, temporary control of cerebrospinal fluid leakage with pulmonary hyperventilation and topical fibrin glue, dissection and vascular-clip ligation of the nerve stump, and capping with a dermis-fat graft. To the authors' knowledge, this postenucleation entity has not been previously described, and asymptomatic idiopathic intracranial hypertension may have been an underlying factor.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Mohun, A. F.; Cook, I. J. Y.

    1962-01-01

    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

  11. Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.

    PubMed

    Isgren, Anniella; Jakobsson, Joel; Pålsson, Erik; Ekman, Carl Johan; Johansson, Anette G M; Sellgren, Carl; Blennow, Kaj; Zetterberg, Henrik; Landén, Mikael

    2015-01-01

    Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. 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

  13. 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

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

    PubMed

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

    1991-01-01

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

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

    PubMed

    Blennow, Kaj; Zetterberg, Henrik

    2013-05-01

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

  16. 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

  17. Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis.

    PubMed

    García-Hernández, Pablo; Prieto, Belén; Martínez-Morillo, Eduardo; Rodríguez, Verónica; Álvarez, Francisco V

    2016-01-01

    Microbiological culture of cerebrospinal fluid is the gold standard to differentiate between aseptic and bacterial meningitis, but this method has low sensitivity. A fast and reliable new marker would be of interest in clinical practice. Interleukin-6, secreted by T cells in response to meningeal pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a marker of acute meningitis. A total of 150 cerebrospinal fluid samples were analysed by an electrochemiluminescence method, selected according to patient diagnosis: (a) bacterial meningitis confirmed by positive culture (n = 26); (b) bacterial meningitis with negative culture or not performed (n = 15); (c) viral meningitis confirmed by polymerase chain reaction or immunoglobulin G determination (n = 23); (d) viral meningitis with polymerase chain reaction negative or not performed (n = 42); and (e) controls (n = 44). Cerebrospinal fluid interleukin-6 concentration showed significant differences between all pathologic groups and the control group (P < 0.001). As a diagnostic tool for bacterial meningitis, interleukin-6 showed an area under the curve of 0.937 (95% confidence intervals: 0.895-0.978), significantly higher than those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5% sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6% sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis. Interleukin-6 measured by electrochemiluminescence method is a promising marker for early differentiation between aseptic and bacterial meningitis. More studies are needed to validate clinical implications for future practice in an emergency laboratory. © The Author(s) 2015.

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

    PubMed

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

    1984-06-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Grevel, V; Machus, B

    1992-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine.

    PubMed

    Duke, B O; Vincelette, J; Moore, P J

    1976-06-01

    Microfilariae of Onchocerca volvulus were found in the cerebrospinal fluid (CSF) of 5/8 heavily infected onchocerciasis patients. During treatment with diethylcarbamazine citrate 10/11 patients showed increased numbers of 0. volvulus microfilariae in the CSF. Patients with concentrations of 8-31 mf/ml CSF developed severe vertigo, and some other neurological manifestations, during treatment. A hypothesis is put forward to account for this clinical piciture, and its importance in relation to the treatment of onchocerciasis is discussed.

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

    PubMed

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

    2015-07-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Amtorp, O; Sorensen, S C

    1974-12-01

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

  6. Spontaneous Intracranial Hypotension Secondary to Lumbar Disc Herniation

    PubMed Central

    Kim, Kyoung-Tae

    2010-01-01

    Spontaneous intracranial hypotension is often idiopathic. We report on a patient presenting with symptomatic intracranial hypotension and pain radiating to the right leg caused by a transdural lumbar disc herniation. Magnetic resonance (MR) imaging of the brain revealed classic signs of intracranial hypotension, and an additional spinal MR confirmed a lumbar transdural herniated disc as the cause. The patient was treated with a partial hemilaminectomy and discectomy. We were able to find the source of cerebrospinal fluid leak, and packed it with epidural glue and gelfoam. Postoperatively, the patient's headache and log radiating pain resolved and there was no neurological deficit. Thus, in this case, lumbar disc herniation may have been a cause of spontaneous intracranial hypotension. PMID:20157378

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

    PubMed

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

    2015-01-01

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

  8. Cerebrospinal fluid otorrhea and pseudomonal meningitis in a child with Mondini dysplasia: case report.

    PubMed

    Hernandez, R Nick; Changa, Abhinav R; Bassani, Luigi; Jyung, Robert W; Liu, James K

    2015-09-01

    Mondini dysplasia is a rare congenital inner ear malformation that presents with abnormal cochlear development with accompanied vestibular dilation and vestibular aqueduct enlargement. This dysfunctional anatomy provides the potential for sensorineural hearing deficits, cerebrospinal fluid leaks, and severe cases of recurrent meningitis. We present the case of a child with Mondini dysplasia who presented with unilateral hearing loss and cerebrospinal fluid (CSF) otorrhea that was surgically repaired through a combined middle fossa/transmeatal middle ear approach to alleviate any recurrence of infection and cerebrospinal fluid otorrhea. Postoperatively, the patient remained neurologically stable without any further CSF leakage. CSF cultures revealed a Pseudomonas aeruginosa infection, a rare occurrence within the context of Mondini dysplasia. Retrograde bacterial spread from the external ear canal into the CSF space has been theorized as the possible pathogenesis of the resulting meningitis. The patient was successfully treated with intravenous antibiotics without any neurologic complications. Although Mondini dysplasia is a rare malformation, the life-threatening sequelae of meningitis that can result from the dysfunctional anatomy makes it a condition that requires elevated clinical vigilance, especially when considering children with hearing loss associated with recurrent meningitis, otorrhea, or rhinorrhea.

  9. Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children

    PubMed Central

    Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

    2017-01-01

    ABSTRACT Objective To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. Methods A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. Results The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. Conclusion Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone. PMID:28767914

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

    SciTech Connect

    Engbaek, F.; Voldby, B

    1982-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Ventricle wall movements and cerebrospinal fluid flow in hydrocephalus.

    PubMed

    Penn, Richard D; Basati, Sukhraaj; Sweetman, Brian; Guo, Xiaodong; Linninger, Andreas

    2011-07-01

    The dynamics of fluid flow in normal pressure hydrocephalus (NPH) are poorly understood. Normally, CSF flows out of the brain through the ventricles. However, ventricular enlargement during NPH may be caused by CSF backflow into the brain through the ventricles. A previous study showed this reversal of flow; in the present study, the authors provide additional clinical data obtained in patients with NPH and supplement these data with computer simulations to better understand the CSF flow and ventricular wall displacement and emphasize its clinical implications. Three NPH patients and 1 patient with aqueductal stenosis underwent cine phase-contrast MR imaging (cine MR imaging) for measurement of CSF flow and ventricle wall movement during the cardiac cycle. These data were compared to data previously obtained in 8 healthy volunteers. The CSF flow measurements were obtained at the outlet of the aqueduct of Sylvius. Calculation of the ventricular wall movement was determined from the complete set of cine MR images obtained axially at the middle of the lateral ventricle. The data were obtained before and after CSF removal with a ventriculoperitoneal shunt with an adjustable valve. To supplement the clinical data, a computational model was used to predict the transmural pressure and flow. In healthy volunteers, net CSF aqueductal flow was 1.2 ml/minute in the craniocaudal direction. In patients with NPH, the net CSF flow was in the opposite direction--the caudocranial direction--before shunt placement. After shunting, the magnitude of the abnormal fluid flow decreased or reversed, with the flow resembling the normal flow patterns observed in healthy volunteers. The authors' MR imaging-based measurements of the CSF flow direction and lateral ventricle volume size change and the results of computer modeling of fluid dynamics lead them to conclude that the directional pattern and magnitude of CSF flow in patients with NPH may be an indication of the disease state. This has

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

    PubMed Central

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

    1984-01-01

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

  14. 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.

  15. Dynamics of cerebrospinal fluid flow in slit ventricle syndrome.

    PubMed

    Eymann, Regina; Schmitt, Melanie; Antes, Sebastian; Shamdeen, Mohammed Ghiat; Kiefer, Michael

    2012-01-01

    Although slit ventricle syndrome (SVS) is identified as a serious complication in shunt-treated hydrocephalus, cerebral spinal fluid (CSF) flow via external ventricular drainage (EVD) or shunts in SVS have not been studied up to now. A new apparatus (LiquoGuard(®); Möller-Medical, Fulda, Germany) was used for EVD in a child with SVS. The LiquoGuard actively controls CSF drainage, based on intracranial pressure (ICP). To achieve well-tolerated clinical conditions, an ICP level of 4 mmHg was necessary; realizable by drainage rates between 0 and 35 mL/h. Drainage rate variations typically occurred with repetitive time intervals of 2 h causing a "saw tooth" shaped CSF flow pattern throughout 24 h. SVS seems to be characterized largely by quickly varying CSF drainage demands. Whether this is a general phenomenon or just true for this case has still to be studied and needs further clarification.

  16. Basic cerebrospinal fluid flow patterns in ventricular catheters prototypes.

    PubMed

    Galarza, Marcelo; Giménez, Ángel; Valero, José; Pellicer, Olga; Martínez-Lage, Juan F; Amigó, José M

    2015-06-01

    A previous study by computational fluid dynamics (CFD) of the three-dimensional (3-D) flow in ventricular catheters (VC) disclosed that most of the total fluid mass flows through the catheter's most proximal holes in commercially available VC. The aim of the present study is to investigate basic flow patterns in VC prototypes. The general procedure for the development of a CFD model calls for transforming the physical dimensions of the system to be studied into a virtual wire-frame model which provides the coordinates for the virtual space of a CFD mesh, in this case, a VC. The incompressible Navier-Stokes equations, a system of strongly coupled, nonlinear, partial differential conservation equations governing the motion of the flow field, are then solved numerically. New designs of VC, e.g., with novel hole configurations, can then be readily modeled, and the corresponding flow pattern computed in an automated way. Specially modified VCs were used for benchmark experimental testing. Three distinct types of flow pattern in prototype models of VC were obtained by varying specific parameters of the catheter design, like the number of holes in the drainage segments and the distance between them. Specifically, we show how to equalize and reverse the flow pattern through the different VC drainage segments by choosing appropriate parameters. The flow pattern in prototype catheters is determined by the number of holes, the hole diameter, the ratio hole/segment, and the distance between hole segments. The application of basic design principles of VC may help to develop new catheters with better flow circulation, thus reducing the possibility of becoming occluded.

  17. 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

  18. Numerical simulation of cerebrospinal fluid hydrodynamics in the healing process of hydrocephalus patients

    NASA Astrophysics Data System (ADS)

    Gholampour, S.; Fatouraee, N.; Seddighi, A. S.; Seddighi, A.

    2017-05-01

    Three-dimensional computational models of the cerebrospinal fluid (CSF) flow and brain tissue are presented for evaluation of their hydrodynamic conditions before and after shunting for seven patients with non-communicating hydrocephalus. One healthy subject is also modeled to compare deviated patients data to normal conditions. The fluid-solid interaction simulation shows the CSF mean pressure and pressure amplitude (the superior index for evaluation of non-communicating hydrocephalus) in patients at a greater point than those in the healthy subject by 5.3 and 2 times, respectively.

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

    PubMed

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

    1996-12-01

    The intracranial distribution of [14C]sucrose, an extracellular marker infused for 30 s into one lateral ventricle, was determined by autoradiography of frozen-dried brain sections. Within 3.5 min [14C]sucrose appeared in: (i) the third ventricle, including optic, infundibular and mammillary recesses; (ii) the aqueduct of Sylvius; (iii) the velum interpositum, a part of the subarachnoid space that runs along the roof of the third ventricle and contains many blood vessels; (iv) the mesencephalic and fourth ventricles; and (v) the superior medullary velum, a highly vascular extension of the subarachnoid space that terminates at the walls of the mesencephalic and fourth ventricles. Within 5 min, radioactivity was present in the interpeduncular, ambient and quadrigeminal cisterns, which encircle the midbrain. By 10 min, approximately 11% of the radioactivity had passed into the subarachnoid space via a previously undescribed flow pathway that included the velum interpositum and superior medullary velum. At many places along the ventricular system, [14C]sucrose appeared to move from cerebrospinal fluid into the adjacent tissue by simple diffusion, as reported previously (Blasberg R. G. et al. (1974) J. Pharmac. exp. Ther. 195, 73-83; Levin V. A. et al. (1970) Am. J. Physiol. 219, 1528-1533; Patlak C. and Fenstermacher J.D. (1975) Am. J. Physiol. 229, 877-884; Rosenberg G. A. and Kyner W.T. (1980) Brain Res. 193, 56-66; Rosenberg G. A. et al. (1986) Am. J. Physiol 251, F485-F489). Little sucrose was, however, taken up by: (i) circumventricular organs such as the subfornical organ; (ii) medullary and cerebellar tissue next to the lateral recesses; and (iii) the superior and inferior colliculi and cerebral peduncles. For the latter two groups of structures, entry from cerebrospinal fluid was apparently blocked by a thick, multilayered glia limitans. Although [14C]sucrose was virtually absent from the rest of the subarachnoid system after 1 h, it remained in the

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

    PubMed

    Csako, Gyorgy

    2012-01-01

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

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

    PubMed

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

    2011-08-01

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

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

    PubMed

    Gorucu, Y; Albayram, S; Balci, B; Hasiloglu, Z I; Yenigul, K; Yargic, F; Keser, Z; Kantarci, F; Kiris, A

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    1994-02-01

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

  5. Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys

    SciTech Connect

    Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.

    1984-05-01

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption.

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

    PubMed

    Fin, Loïc; Grebe, Reinhard

    2003-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-03-23

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

  9. 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. © 2015 American Heart Association, Inc.

  10. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition.

    PubMed

    Goos, Jeroen D C; Kester, M I; Barkhof, Frederik; Klein, Martin; Blankenstein, Marinus A; Scheltens, Philip; van der Flier, Wiesje M

    2009-11-01

    Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers. Patients with Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female) and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined. Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group. Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.

  11. 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.

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

    PubMed

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

    1981-02-01

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

  13. Gastrin and cholecystokinin in human cerebrospinal fluid. Immunochemical determination of concentrations and molecular heterogeneity.

    PubMed

    Rehfeld, J F; Kruse-Larsen, C

    1978-10-20

    To determine whether gastrin and cholecystokinin (CCK), recently found in the central nervous sytem, were present in cerebrospinal fluid (CSF), we studied human specimens by sensitive and specific radioimmunoassays for the two related polypeptide hormones. The concentration of gastrin in cerebrospinal fluid from 10 neurologically normal persons ranged from 1.5 to 8.0 pM (mean 3.4 pM), whereas the concentration of CCK ranged from 4 to 55 pM (mean 14 pM). The molecular heterogeneity of gastrin and CCK in CSF was determined by gel chromatography of concentrated fluid monitored by 3 gastrin radioimmunoassays specific for different sequences of gastrin17 and 3 CCK radioimmunoassays specific for different sequences of CCK33. Chromatography revealed that gastrin was present in molecular forms corresponding to gastrin34 ('big gastrin') and gastrin17. CCK was present in molecular forms corresponding to the COOH-terminal octapeptide amide of CCK33 and a fragment corresponding to sequence 25-29 of CCK33. Also, a peptide corresponding to COOH-terminal tetrapeptide amide common to both gastrin and CCK was found. The results indicate that true gastrin as well as CCK are present in CSF, and that both hormones display a molecular heterogeneity similar to that found in extracts of brain tissue.

  14. An update on the use of cerebrospinal fluid analysis as a diagnostic tool in multiple sclerosis.

    PubMed

    Gastaldi, Matteo; Zardini, Elisabetta; Franciotta, Diego

    2017-01-01

    Intrathecal B-lymphocyte activation is a hallmark of multiple sclerosis (MS), a multi-factorial inflammatory-demyelinating disease of the central nervous system. Such activation has a counterpart in the cerebrospinal fluid (CSF) oligoclonal IgG bands (OCB), whose diagnostic role in MS has been downgraded within the current McDonald's criteria. With a theoretico-practical approach, the authors review the physiopathological basis of the CSF dynamics, and the state-of-the-art of routine CSF analysis and CSF biomarkers in MS. Areas covered: The authors discuss pros and cons of CSF analysis, including critical evaluations of both well-established, and promising diagnostic and prognostic laboratory tools. New acquisitions on the CSF and cerebral interstitial fluid dynamics are also presented. The authors searched the PubMed database for English-language articles reported between January 2010 and June 2016, using the key words 'multiple sclerosis', 'cerebrospinal fluid', 'oligoclonal bands'. Reference lists of relevant articles were scanned for additional studies. Expert commentary: The availability of performing high-quality, routine CSF tests in specialized laboratories, the emerging potential of novel CSF biomarkers, and the trend for early treatments should induce a reappraisal of CSF analysis for diagnostic and prognostic purposes in MS. Further procedural and methodological improvements seem to be necessary in both research and translational diagnostic CSF settings.

  15. Broadband Infrared Spectroscopy for Non-Contact Measurement of Neurological Disease Biomarkers in Cerebrospinal Fluid.

    PubMed

    Horosh, Michael; Feldman, Haim; Yablonovich, Avi; Firer, Michael A; Abookasis, David

    2017-03-01

    Cerebrospinal fluid (CSF) is a clear and colorless biological fluid which circulates within brain ventricles (cavities), the spinal cord's central canal, the space between the brain and the spinal cord, as well as their protective coverings, the meninges. Cerebrospinal fluid contains different constituents, such as albumin and lactate, whose levels are used clinically as biomarkers of neurodegenerative disorders. In current clinical practice, analysis of CSF content for the diagnosis of central nervous system disorders requires an invasive procedure known as lumbar puncture or spinal tap. With the aim of developing a noninvasive alternative, we report here the spectral behavior of albumin and lactate over a broad wavelength range of 600-2000 nm, after each was added separately at varying normal and abnormal concentration levels to artificial CSF ( aCSF). Spectral measurements were conducted simultaneously by two different spectrometers working at different spectral ranges in transmittance mode. Spectral analysis revealed that albumin and lactate each possesses its own first and second derivative absorbance spectra fingerprint between 1660 and 1810 nm. Distinguishing albumin from lactate by their spectral data enabled the differentiation between aCSF conditions modeling different neurological disorders. Spectral changes of each compound strongly correlated ( R(2 )> 0.9) with absorbance derivative spectra peaks at specific wavelengths, when analyzed by linear regression with variations in their concentration. These findings suggest the feasibility of CSF biomarker assessment by broadband infrared spectroscopy.

  16. PENETRATION OF RADIOACTIVE SODIUM AND CHLORIDE INTO CEREBROSPINAL FLUID AND AQUEOUS HUMOR

    PubMed Central

    Wang, Jun-Ch'uan

    1948-01-01

    1. Experiments were performed on six dogs to determine the rate of penetration of Cl33 and Na24 across the blood-aqueous humor and blood-cerebrospinal fluid barriers after intravenous injection of the radioactive ions. The radioactivity measurements were made with an immersion type of Geiger-Müller counter. 2. The concentrations of the labelled ions in the anterior chamber and the cisterna magna increase slowly to approach that of plasma. The rate of penetration k is calculated from a simple exponential equation with the half-value interval t0.5 or the time required for the labelled-ion concentration in the fluid to reach 50 per cent of that of plasma. The average t0.5 for Cl38 and Na24 in aqueous humor are 34.3 ± 9 and 27.3 ± 9 minutes, respectively, while those for cerebrospinal fluid are 90 ± 6 and 95 ± 6 minutes, respectively. 3. A study of the radioactivity in plasma was made to determine the per cent remaining after a steady state was reached. By means of this determination the sodium and chloride space was calculated to be 33 ± 5 per cent. PMID:18920614

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

    PubMed

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

    2015-03-01

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

  18. [Prognostic value of VZV PCR in cerebrospinal fluid in neurological manifestations of varicella].

    PubMed

    Levy, M; Hentgen, V; Marque-Juillet, S; Fiot, E; Fagherazzi, G; Nathanson, S; Foucaud, P

    2015-05-01

    Varicella-zoster virus (VZV) is, like other alphaherpes viruses, neurotropic. Of the admissions to hospital for varicella, 7.6-25% are due to neurologic manifestations. Most of the time, the concomitant skin lesions facilitate the diagnosis. The justification of qualitative PCR (polymerase chain reaction) for VZV DNA in cerebrospinal fluid in the management of these patients is not clear. The aim of this study was to evaluate the prognostic value of qualitative PCR for VZV DNA in cerebrospinal fluid and to assess its impact on patient management. We conducted a retrospective monocentric study in Versailles Hospital (France). It included every child admitted for neurologic manifestations associated with varicella and compared the patients with positive PCR for VZV DNA to those with a negative PCR in the cerebrospinal fluid. Seven patients with positive PCR and 16 patients with negative PCR were included. The median age of the children included was 3 years (range, 1.6-12 years) and 2 years (range, 0.6-5 years), respectively. In the positive PCR group, 86% of the children had fever on first examination and the average time between the onset of skin lesions and neurological signs was +1.28 days (range, -2 to +5 days). In comparison, in the negative PCR group, 81% of the children had fever and the average time delay was +1.75 days (-2 to +7 days). There was no significant difference in terms of length of hospitalization; 3 days (range, 0-6 days) and 3 days (range, 2-7 days), respectively. All patients discharged from our department went home. In addition, there was no significant difference between the two groups in terms of treatment with acyclovir; two children (28.5%) were treated in the positive PCR group versus four (25%) in the negative PCR group. Our study showed no prognostic value for qualitative PCR for VZV DNA in the cerebrospinal fluid of patients with neurologic manifestations of varicella. Therefore, its relevance can be questioned in clinical practice

  19. Non Invasive Microwave Sensor for the Detection of Lactic Acid in Cerebrospinal Fluid (CSF)

    NASA Astrophysics Data System (ADS)

    Goh, J. H.; Mason, A.; Al-Shamma'a, A. I.; Field, M.; Shackcloth, M.; Browning, P.

    2011-08-01

    This research involves the use of a low power microwave sensor for analysis of lactic acid in cerebrospinal fluid (CSF), an indicator of neurological impairment during aortic aneurysm surgery which could provide the basis for improved treatment regimes and better quality of care with more efficient use of resources. This paper presents initial work using standard lactate curves in water followed by lactate in "synthetic CSF". A multi-modal spectral signature has been defined for lactate, forming the basis for subsequent development of microwave sensor platform that is able to detect concentrations of lactic acid in CSF of volumes less than 1ml.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

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

  2. Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

    PubMed

    Jiménez-Jiménez, F J; Hernánz, A; Medina-Acebrón, S; de Bustos, F; Zurdo, J M; Alonso, H; Puertas, I; Barcenilla, B; Sayed, Y; Cabrera-Valdivia, F

    2005-02-01

    To elucidate whether cerebrospinal fluid (CSF) concentrations of the microtubule-associated tau protein are related to the risk for sporadic amyotrophic lateral sclerosis (SALS). We measured tau concentrations in the CSF of 18 patients with SALS and 75 age- and sex-matched controls, using a specific ELISA method. The mean CSF concentrations of tau protein did not differ significantly between SALS patient and control groups, were not influenced by the clinical form (spinal vs bulbar) of ALS, and were not correlated with age, age at onset, and duration of the disease. CSF tau concentrations are not a biochemical marker of ALS.

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

    PubMed

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

    2016-12-01

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

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

    PubMed

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

    2013-11-01

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

  5. Amino acid concentrations in cerebrospinal fluid: effects of aging, depression, and probenecid.

    PubMed

    Goodnick, P J; Evans, H E; Dunner, D L; Fieve, R R

    1980-08-01

    Cerebrospinal fluid (CSF) amino acid concentrations were measured in six Bipolar I, eight Bipolar II, eight Unipolar, and four other and control patients. All but four were also studied after administration of probenecid. Fourteen amino acids showed significant correlations of concentrations with age of subjects. Significant diagnostic group differences were found for five amino acids; only that of tyrosine persisted after taking subject's age into account. Following probenecid administration, there were statistically significant changes in CSF concentration of several amino acids, but these changes were small and likely indicative of diurnal changes.

  6. 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

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

    PubMed

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

    2016-10-27

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

  8. [Cerebrospinal fluid pressure studies after the intravenous administration of the steroid narcotic, alphaxolone + alphadolone acetate (Althesin)].

    PubMed

    Ekhart, E; List, W F; Vadon, P; Oberbauer, R

    1979-09-30

    The effect of alphaxalon + alphadolon-acetate on cerebrospinal fluid pressure (CSFP), mean arterial blood pressure (MPA), heart rate (BMP) and blood gases was investigated in 18 patients. Cerebral perfusion pressure (CPP) was calculated from the difference MAP minus CSFP. Alphaxalon + alphadolon-acetate lowered the normal CSFP and normalized ketamin induced increase of CSFP. Premedication with alphaxalon + alphadolon-acetate delayed the ketamin induced increase of CSFP, which returned to norm after a second dose of alphaxalon + alphadolon-acetate. This effect was seen despite elevation of pCO2 in all patients breathing spontaneously.

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

    PubMed Central

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

    2010-01-01

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

  10. 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

  11. [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. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  13. 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.

  14. 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

  15. 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

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

    PubMed

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

    2012-10-01

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

  17. [Transthyretin levels in serum and cerebrospinal fluid sustain the nutrio-viral hypothesis of the Cuban epidemic neuropathy].

    PubMed

    Dorta-Contreras, A J; Barshatzky, M; Noris-García, E; Serrano-Sánchez, T

    Transthyretin is considered an excellent marker for monitoring nutritional status in serum. In cerebrospinal fluid it is synthesized by chroroid plexus. Cuban epidemic neuropathy is an emergent disease with a hypothetically viral and nutritional origin. To know the behavior of this transport molecule in serum and cerebrospinal fluid in patients with Cuban epidemic neuropathy. Serum and cerebrospinal fluid was quantified in 11 patients with Cuban epidemic neuropathy, eight patients suffering from other neuropathies and 15 patients with Down's syndrome and 10 patients with Alzheimer's disease. Serum transthyretin was diminished in patients with Cuban epidemic neuropathy, other neuropathies and Alzheimer's disease. Down's syndrome patients had significantly higher transthyretin levels in comparison with Cuban epidemic neuropathy and Alzheimer's disease. Cerebrospinal fluid transthyretin was significantly increased in patients with Cuban epidemic neuropathy in comparison with the normal values and with Alzheimer's disease patients whose values were settled below the normal values. The decrement of serum transthyretin in Cuban epidemic neuropathy indicates malnutrition and its higher levels in cerebrospinal fluid also indicate a viral infection. These findings support the nutrio-viral hypothesis of the disease.

  18. Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels.

    PubMed

    Sariego-Jamardo, Andrea; García-Cazorla, Angels; Artuch, Rafael; Castejón, Esperanza; García-Arenas, Dolores; Molero-Luis, Marta; Ormazábal, Aida; Sanmartí, Francesc Xavier

    2015-11-01

    The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Vaginal Migration of Ventriculoperitoneal Shunt Catheter and Cerebrospinal Fluid Leak as a Complication of Hysterectomy.

    PubMed

    Houten, John K; Smith, Shiela; Schwartz, Amit Y

    2017-08-01

    Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure to treat hydrocephalus that diverts cerebrospinal fluid from the cerebral ventricles to the peritoneal cavity for reabsorption. The distal catheter may potentially migrate through any potential or iatrogenic opening in the peritoneal cavity. Increasingly successfully management of childhood hydrocephalus and adult-onset conditions leading to hydrocephalus, such as subarachnoid hemorrhage, is leading many adult female patients harboring VP shunts needing to undergo hysterectomy. Hysterectomy creates a potential defect though which a VP shunt catheter may migrate. It is not known whether the hysterectomy cuff closure technique may affect the likelihood of distal catheter migration though the repair site. We report the case of a 38-year-old woman with a VP shunt who underwent laparoscopic hysterectomy via an open vaginal cuff technique who subsequently presented with vaginal cerebrospinal fluid leakage secondary to migration of the distal shunt catheter through the hysterectomy cuff. Vaginal migration of the distal VP shunt catheter is a possible complication of hysterectomy. The authors postulate that an open cuff hysterectomy closure technique may increase the risk of catheter migration, an issue that may be better understood with further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Clinical and cerebrospinal fluid findings contribute to the early differentiation between infectious and noninfectious encephalitis.

    PubMed

    Wilken, Miguel; Ameghino, Lucía; Cammarota, Ángel; Nogués, Martín A; Del Castillo, Marcelo; Farez, Mauricio F

    2017-01-01

    Early recognition and prompt specific treatment are crucial factors influencing the outcome of patients with acute encephalitis. The aim of this study was to determine the main causes of acute encephalitis in our population and to find predictors that may lead to specific diagnosis. Adult patients admitted to our hospital with suspected diagnosis of encephalitis in the period 2006-2013 were included. One hundred and five medical records were analyzed. Eighty-two patients with infectious encephalitis were identified (78% of total cases), 53 (65%) men and 29 (35%) women, mean age 47.8 years. The most common microorganisms identified were: HSV-1 (11%), VZV (10%), HSV-2 (5%) and EBV (5%). Twenty-three patients (22% of the series) had non-infectious encephalitis. Headache (p < 0.0001) and fever (p = 0.008) were more frequent in encephalitis of infectious origin. Protein levels and white blood cell counts in the cerebrospinal fluid were significantly higher in patients affected by infectious encephalitis than in those affected by noninfectious encephalitis (OR 95% CI 12.3 [2.9-51.7] and OR 95% CI 7.4 [2-27], respectively). Identifying specific causal agents of acute encephalitis remains a major challenge. Cerebrospinal fluid markers, as well as specific clinical findings, may however contribute to initial differentiation between infectious and noninfectious causes.

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

    PubMed

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

    1989-05-01

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

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

    PubMed

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

    2005-11-01

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

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

    PubMed

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

    2004-12-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Strzelak, Kamil; Wiśniewska, Agnieszka; Bobilewicz, Dagna; Koncki, Robert

    2014-10-01

    A fully mechanized, computer-controlled, multicommutated flow analysis (MCFA) system dedicated for total protein determination in cerebrospinal fluid samples has been developed. For the protein determination the Exton method has been applied. Dedicated turbidimetric and nephelometric flow-through detectors operating according to paired-emitter detector diode principle have been fabricated by integration of two or three respective light emitting diodes. The developed MCFA system is characterized by robust, compact design and low consumption of the sample (72 μ L). The limits of detection for turbidimetric and nephelometric detection mode are 65 mg L(-1) and 9 mg L(-1), respectively. For turbidimetric measurements the range of linear response offered by the MCFA system is 72-900 mg L(-1), whereas in the case of nephelometric detection 18-500 mg L(-1) linear range is obtained. The throughput of the MCFA system is over 30 injection per hour. The analytical system was optimized with bovine serum albumin standards and successfully validated with real samples of human cerebrospinal fluid. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-01-01

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

  7. Performance of Cerebrospinal Fluid Biomarkers of Alzheimer Disease in a Memory Clinic in Norway.

    PubMed

    Knapskog, Anne-Brita; Engedal, Knut; Braekhus, Anne

    2016-01-01

    Although Alzheimer disease (AD) remains a clinical diagnosis, biomarkers are in use to support the diagnosis. Three cerebrospinal biomarkers, amyloid-β (Aβ), total tau (T-tau), and phospho tau (P-tau), reflect neuropathologic changes observed in AD patients. The aim of this study was to explore the performance of the cerebrospinal fluid biomarkers used in a memory clinic setting. We included 205 patients who had been through a standardized examination including lumbar puncture. Diagnoses were made blind to the results of the spinal fluid analyses. By combining low Aβ and high T-tau or P-tau values, the sensitivity was 31.9% and the specificity was 92.5% when comparing patients with AD with other patients. In receiver operating characteristic analyses, the AUC for the Aβ was 0.78 (SE=0.04; 95% CI, 0.7-0.85), for T-tau 0.80 (SE=0.03; 95% CI, 0.73-0.86), and for P-tau 0.76 (SE=0.04; 95% CI, 0.69-0.83). A significant difference was found between the sexes, with higher values of Aβ among younger men (under 65 y of age) with AD [799.8 (SD=317.2) vs. 558.9 (SD=123.5) for women, P-value=0.003]. The present study found a lower performance of the biomarkers than reported previously.

  8. 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

  9. Ketogenic diet fed rats have low levels of S100B in cerebrospinal fluid.

    PubMed

    Ziegler, Denize R; Oliveira, Diogo L; Pires, Caroline; Ribeiro, Letícia; Leite, Marina; Mendez, Andreas; Gonçalves, Daniela; Tramontina, Francine; Portela, Luis V; Wofchuk, Susana T; Perry, Marcos L; Gonçalves, Carlos-Alberto

    2004-12-01

    Ketogenic diets have been used to treat seizure disorders of children resistant to conventional anti-epileptic drug treatment. The mechanism of action of this diet, however, is unknown. Gliosis is a very common characteristic in tissues associated with epileptogenesis and glial cytokines may be involved in the pathology of seizure disorders. We investigate herein, whether ketogenic diet fed rats demonstrate changes in the immunocontent of S100B, an astrocyte-derived cytokine elevated in the temporal lobe of refractory epilepsy. Lower levels of S100B were observed in cerebrospinal fluid with no significant changes in S100B and GFAP content in brain tissue. Ketogenic fed rats presented a lower seizure severity induced by pentylenetetrazole and no change in cerebrospinal fluid S100B after pentylenetetrazole administration. These results support the concept that the ketogenic diet is neuroprotective in seizure disorders. Since S100B has an extracellular activity in neuronal excitability and synaptic plasticity, it would be reasonable to conceive that a decrease in the S100B could be involved in the mechanism of action of the ketogenic diet. However, it is not possible to establish a direct link between reduced CSF S100B and decreased severity of PTZ-induced attacks at present moment. Regardless of this, CSF S100B could be proposed as an index of efficacy of ketogenic diet for seizure disorders.

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

    PubMed Central

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

    2012-01-01

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

  11. GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.

    PubMed

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

    2013-04-24

    Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Aβ₄₂ are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10⁻⁹ for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10⁻⁸ and p = 3.22 × 10⁻⁹ for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10⁻⁸ for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10⁻⁴, 0.039, 4.86 × 10⁻⁵, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer's disease.

    PubMed

    Kessler, H; Pajonk, F-G; Meisser, P; Schneider-Axmann, T; Hoffmann, K-H; Supprian, T; Herrmann, W; Obeid, R; Multhaup, G; Falkai, P; Bayer, T A

    2006-11-01

    Increasing evidence links Alzheimer's disease (AD) with misbalanced Cu homeostasis. Recently, we have shown that dietary Cu supplementation in a transgenic mouse model for AD increases bioavailable brain Cu levels, restores Cu, Zn-super oxide-1 activity, prevents premature death, and lowers A beta levels. In the present report we investigated AD patients with normal levels of A beta 42, Tau and Phospho-Tau in the cerebrospinal fluid (CSF) in comparison with AD patients exhibiting aberrant levels in these CSF biomarkers. The influence of these cerebrospinal fluid (CSF) diagnostic markers with primary dependent variables blood Cu, Zn and ceruloplasmin (CB) and secondary with CSF profiles of Cu, Zn and neurotransmitters was determined. Multivariate tests revealed a significant effect of factor diagnostic group (no AD diagnosis in CSF or AD diagnosis in CSF) for variables plasma Cu and CB (F=4.80; df=2, 23; p=0.018). Subsequent univariate tests revealed significantly reduced plasma Cu (-12.7%; F=7.05; df=1, 25; p=0.014) and CB (-14.1%; F=9.44; df=1, 24; p=0.005) levels in patients with aberrant CSF biomarker concentrations. Although only AD patients were included, the reduced plasma Cu and CB levels in patients with a CSF diagnosis of advanced AD supports previous observations that a mild Cu deficiency might contribute to AD progression.

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Orthostatic Hypotension (Postural Hypotension)

    MedlinePlus

    ... happens, you may be asked to wear a 24-hour Holter monitor to record your heart's electrical activity ... medications for people who aren't helped with lifestyle changes or other medications. There are many simple steps to managing or preventing orthostatic hypotension. Your doctor may give ...

  16. Liquor cotunnii: the history of cerebrospinal fluid in Domenico Cotugno's work.

    PubMed

    Di Ieva, Antonio; Yaşargil, M Gazi

    2008-08-01

    Domenico Cotugno was a famous physician who lived in Naples in the 18th century. At the age of only 25 years, he published an important book on the anatomy of the inner ear that contained some theories concerning the physiology of hearing, the later developments of which were associated with the name of Hermann von Helmholtz. Three years later, he wrote a book on the physiopathological causes of sciatic pain, in which, for the first time in medical history, he differentiated true sciatic pain from the pain attributable to secondary causes. Using a series of meticulous dissections and elegant experiments, he showed that not only brain ventricles but also the subarachnoid spaces of the cranium and spine were filled with circulating fluid, which is why cerebrospinal fluid is also known as "liquor cotunnii."

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

    PubMed

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

    2017-03-14

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

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

    PubMed

    Chikly, Bruno; Quaghebeur, Jörgen

    2013-07-01

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

  19. Alzheimer's disease: roles for mitochondrial damage, the hydroxyl radical, and cerebrospinal fluid deficiency of melatonin.

    PubMed

    Maurizi, C P

    2001-08-01

    A deficiency of cerebrospinal fluid melatonin is postulated to be critical for the development of Alzheimer's disease. Some melatonin is normally secreted directly into the fluid inducing higher levels than in simultaneously sampled blood. Melatonin is carried into the ventricular system via choroid plexus portals. The neurohormone is a potent antioxidant that passes through cell membranes with ease and is concentrated in mitochondria. Neural tissue in contact with the ventricular system will have high levels of cellular melatonin. In Alzheimer's disease, inadequate melatonin allows hydroxyl radicals produced by mitochondrial complex IV to damage mitochondria and initiate a cascade of oxygen radicals that causes the neuropathological changes in Alzheimer's disease. Results from initial therapeutic trials of melatonin in Alzheimer's disease patients have demonstrated improved function, decreased 'sundowning', improved sleep, and a significant slowing of the progression of the disease. Copyright 2001 Harcourt Publishers Ltd.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Identification of Oropouche Orthobunyavirus in the cerebrospinal fluid of three patients in the Amazonas, Brazil.

    PubMed

    Bastos, Michele de Souza; Figueiredo, Luiz Tadeu Moraes; Naveca, Felipe Gomes; Monte, Rossicleia Lins; Lessa, Natália; Pinto de Figueiredo, Regina Maria; Gimaque, João Bosco de Lima; Pivoto João, Guilherme; Ramasawmy, Rajendranath; Mourão, Maria Paula Gomes

    2012-04-01

    Oropouche fever is the second most frequent arboviral infection in Brazil, surpassed only by dengue. Oropouche virus (OROV) causes large and explosive outbreaks of acute febrile illness in cities and villages in the Amazon and Central-Plateau regions. Cerebrospinal fluid (CSF) samples from 110 meningoencephalitis patients were analyzed. The RNA extracted from fluid was submitted to reverse transcription-polymerase chain reaction and sequencing to identify OROV. Three CSF samples showed the presence of OROV causing infection in the central nervous system (CNS). These patients are adults. Two of the patients had other diseases affecting CNS and immune systems: neurocysticercosis and acquired immunodeficiency syndrome, respectively. Nucleotide sequence analysis showed that the OROV from the CSF of these patients belonged to genotype I. We show here that severe Oropouche disease is occurring during outbreaks of this virus in Brazil.

  4. Endoscopic Endonasal Repair of Cerebrospinal Fluid Leakage Caused by a Rare Traumatic Clival Fracture

    PubMed Central

    HIRAYAMA, Akihiro; KOMATSU, Fuminari; HOTTA, Kazuko; IMAI, Masaaki; ODA, Shinri; SHIMODA, Masami; MATSUMAE, Mitsunori

    2016-01-01

    An 89-year-old male presented with cerebrospinal fluid (CSF) rhinorrhea associated with head trauma sustained as a pedestrian in a traffic accident. Computed tomography (CT) showed pneumocephalus and multiple cranial bone fractures, including the clivus. Although the CSF rhinorrhea was treated conservatively for a week, clinical symptoms did not improve and surgical repair was performed. Preoperative thin-sliced bone CT and steady-state magnetic resonance images revealed a bone defect at the middle clivus and a collection of CSF fluid from the clival fistula in the sphenoid sinus. Endoscopic endonasal reconstruction was performed, and the 3-mm diameter dural tear and bone defect at the middle clivus were well visualized. The fistula was repaired using a pedicled nasoseptal mucosal flap. The CSF rhinorrhea completely disappeared as a result of the endoscopic endonasal surgery. The present report describes a rare case of CSF rhinorrhea caused by a traumatic clival fracture and surgical management by endoscopic endonasal surgery. PMID:26804187

  5. Soluble CD27 Levels in Cerebrospinal Fluid as a Prognostic Biomarker in Clinically Isolated Syndrome.

    PubMed

    van der Vuurst de Vries, Roos M; Mescheriakova, Julia Y; Runia, Tessel F; Jafari, Naghmeh; Siepman, Theodora A M; Hintzen, Rogier Q

    2017-03-01

    There is a growing number of therapies that could be administered after the first symptom of central nervous system demyelination. These drugs can delay multiple sclerosis (MS) diagnosis and slow down future disability. However, treatment of patients with benign course may not be needed; therefore, there is a need for biomarkers to predict long-term prognosis in patients with clinically isolated syndrome (CIS). To investigate whether the T-cell activation marker soluble CD27 (sCD27) measured in cerebrospinal fluid of patients at time of a first attack is associated with a subsequent diagnosis of MS and a higher relapse rate. This prospective study included 77 patients with CIS between March 2002 and May 2015 in a tertiary referral center for multiple sclerosis, in collaboration with several regional hospitals. Patients with CIS underwent a lumbar puncture and magnetic resonance imaging scan within 6 months after first onset of symptoms. Soluble CD27 levels were determined in cerebrospinal fluid using a commercially available enzyme-linked immunosorbent assay. Cox regression analyses was used to calculate univariate and multivariate hazard ratios for MS diagnosis. Association between sCD27 levels and relapse rate was assessed using a negative binomial regression model. Among 77 patients with CIS, 50 were female (79.5%), and mean (SD) age was 32.7 (7.4) years. Mean (SD) age in the control individuals was 33.4 (9.5) years, and 20 were female (66.7%).Patients with CIS had higher cerebrospinal fluid sCD27 levels than control individuals (geometric mean, 31.3 U/mL; 95% CI, 24.0-40.9 vs mean, 4.67 U/mL; 95% CI, 2.9-7.5; P < .001). During a mean (SD) follow-up of 54.8 (35.1) months, 39 of 77 patients (50.6%) were diagnosed as having MS. In a model adjusted for magnetic resonance imaging and cerebrospinal fluid measurements, sCD27 levels were associated with a diagnosis of MS (hazard ratio, 2.4 per 100 U/mL increase in sCD27 levels; 95% CI, 1.27-4.53; P = .007

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

    PubMed Central

    Cherebillo, Vyacheslav Yu.; Polegaev, Andrei V.

    2015-01-01

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

  7. Effects of fluid preload (crystalloid or colloid) compared with crystalloid co-load plus ephedrine infusion on hypotension and neonatal outcome during spinal anaesthesia for caesarean delivery.

    PubMed

    Gunusen, I; Karaman, S; Ertugrul, V; Firat, V

    2010-07-01

    Preload with crystalloid or colloid solution is widely recommended for the prevention of maternal hypotension during spinal anaesthesia. A combination of simultaneous rapid crystalloid infusion with vasopressor has also been suggested. This study tested the hypothesis that ephedrine infusion with crystalloid loading at spinal anaesthesia would reduce hypotension and alter neonatal outcome compared with fluid preloading. One hundred and twenty women undergoing elective caesarean delivery were randomly allocated to one of three groups to receive rapid infusion of lactated Ringer's solution (20 ml.kg(-1), n=40) or 4% succinylated gelatin solution (500 ml, n =40) before spinal anaesthesia or an ephedrine infusion (1.25 mg.minute(-1)) plus lactated Ringer's solution (1000 ml, n=40) after spinal anaesthesia. The incidence of hypotension (moderate and severe) and the ephedrine dose used to treat hypotension were compared. Neonatal outcome was assessed using Apgar scores and umblical venous and arterial blood gas analysis. The frequency of moderate or severe hypotension was lower in the ephedrine group than in the crystalloid or colloid preload group (10% vs. 51% and 38%; 5% vs. 21% and 23% respectively, P < 0.05). The incidence of nausea was significantly different between the crystalloid preload and ephedrine group. Umbilical blood gas analysis and Apgar scores were similar in all groups. A combination of an ephedrine infusion at 1.25 mg.minute(-1) with a crystalloid co-load was more effective than fluid preloading with crystalloid or colloid in the prevention of moderate and severe hypotension.

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

    PubMed

    Králová, E; Novotná, H; Adam, Z

    1993-12-20

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

    Walusinski, Olivier

    2014-03-01

    Yawning is a behavior to which little research has been devoted. However, its purpose has not yet been demonstrated and remains controversial. In this article, we propose a new theory involving the brain network that is functional during the resting state, that is, the default mode network. When this network is active, yawning manifests a process of switching to the attentional system through its capacity to increase circulation of cerebrospinal fluid (CSF), thereby increasing clearance of somnogenic factors (prostaglandin D(2), adenosine, and others) accumulating in the cerebrospinal fluid. Copyright © 2013 Wiley Periodicals, Inc.

  11. Sample-dependent diagnostic accuracy of prostaglandin D synthase in cerebrospinal fluid leak.

    PubMed

    Morell-Garcia, Daniel; Bauça, Josep Miquel; Sastre, M Pilar; Yañez, Aina; Llompart, Isabel

    2017-01-01

    Prostaglandin D2 synthase, commonly known as β-trace protein (βTP), is an excellent biomarker for the assessment of cerebrospinal fluid (CSF) leaks. Despite being widely used, the limits for the diagnostic values of βTP are not well established to date, and currently suggested cut-off values in literature range from 0.25 to 6.0mg/L. Sample-specific and more accurate thresholds are a current need. A retrospective observational study, performed in a tertiary-care hospital, between January 2006 and January 2014. A total of 74 patients were included, with a definitive diagnosis after initial leak suspicion and at least one determination of βTP using a nephelometry-based assay. A total of 46 CSF samples were included in the control group. Samples were obtained from nasal secretions, ear secretions or spinal surgical injury, directly using sterile Eppendorf tubes. The analysis of 3 different cut-off values was performed and the receiver operating curve (ROC) analyses were calculated. Initial diagnostic suspicion was confirmed in 51% of cases, most of which were of postoperative origin (51%) and traumatic (26%). The βTP median concentration in different samples was significantly higher in the presence of cerebrospinal fluid fistula, regardless of sample type (22.0mg/L vs. 0.24mg/L, 95% confidence interval: 19.0-30.8 vs. 0.08-0.40; p<0.001). Data from contingency tables show 100% sensitivity and specificity, depending on sample type and the cut-off value used: for rhinorrhea and otorrhea samples, the most appropriate it was 0.7mg/L, while values >2.0mg/L could be used for spine postoperative fluid leakage samples. The cut off value for βTP in the diagnosis and follow-up of cerebrospinal fluid leaks should be modified depending on the type of secretion (sample type), for a better diagnostic accuracy. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2006-01-01

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

  13. 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

  14. Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression.

    PubMed

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

    2016-01-01

    The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = -4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and faster white matter intensity change (

  15. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial.

    PubMed

    Schwarzschild, Michael A; Ascherio, Alberto; Beal, M Flint; Cudkowicz, Merit E; Curhan, Gary C; Hare, Joshua M; Hooper, D Craig; Kieburtz, Karl D; Macklin, Eric A; Oakes, David; Rudolph, Alice; Shoulson, Ira; Tennis, Marsha K; Espay, Alberto J; Gartner, Maureen; Hung, Albert; Bwala, Grace; Lenehan, Richard; Encarnacion, Elmyra; Ainslie, Melissa; Castillo, Richard; Togasaki, Daniel; Barles, Gina; Friedman, Joseph H; Niles, Lisa; Carter, Julie H; Murray, Megan; Goetz, Christopher G; Jaglin, Jeana; Ahmed, Anwar; Russell, David S; Cotto, Candace; Goudreau, John L; Russell, Doozie; Parashos, Sotirios Andreas; Ede, Patricia; Saint-Hilaire, Marie H; Thomas, Cathi-Ann; James, Raymond; Stacy, Mark A; Johnson, Julia; Gauger, Lisa; Antonelle de Marcaida, J; Thurlow, Sheila; Isaacson, Stuart H; Carvajal, Lisbeth; Rao, Jayaraman; Cook, Maureen; Hope-Porche, Charlise; McClurg, Lauren; Grasso, Daniela L; Logan, Robert; Orme, Constance; Ross, Tori; Brocht, Alicia F D; Constantinescu, Radu; Sharma, Saloni; Venuto, Charles; Weber, Joseph; Eaton, Ken

    2014-02-01

    Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled. Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. The prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid. RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs

  16. Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.

    PubMed

    Lautner, Ronald; Palmqvist, Sebastian; Mattsson, Niklas; Andreasson, Ulf; Wallin, Anders; Pålsson, Erik; Jakobsson, Joel; Herukka, Sanna-Kaisa; Owenius, Rikard; Olsson, Bob; Hampel, Harald; Rujescu, Dan; Ewers, Michael; Landén, Mikael; Minthon, Lennart; Blennow, Kaj; Zetterberg, Henrik; Hansson, Oskar

    2014-10-01

    Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown. To evaluate whether the APOE genotype affects the diagnostic accuracy of CSF biomarkers for Alzheimer disease (AD), in particular Aβ42 levels, and whether the association of APOE ε4 with CSF biomarkers depends on cortical Aβ status. We collected data from 4 different centers in Sweden, Finland, and Germany. Cohort A consisted of 1345 individuals aged 23 to 99 years with baseline CSF samples, including 309 with AD, 287 with prodromal AD, 399 with stable mild cognitive impairment, 99 with dementias other than AD, and 251 controls. Cohort B included 105 nondemented younger individuals (aged 20-34 years) with CSF samples available. Cohort C included 118 patients aged 60 to 80 years with mild cognitive symptoms who underwent flutemetamol F 18 ([18F]flumetamol) positron emission tomography amyloid imaging and CSF tap. Standard care. Cerebrospinal fluid levels of Aβ42 and total and phosphorylated tau in relation to the APOE ε2/ε3/ε4 polymorphism in different diagnostic groups and in cases with or without cortical uptake of [18F]flutemetamol. The CSF levels of Aβ42 but not total and phosphorylated tau were lower in APOE ε4 carriers compared with noncarriers irrespective of diagnostic group (cohort A). Despite this, CSF levels of Aβ42 differed between participants with AD when compared with controls and those with stable mild cognitive impairment, even when stratifying for APOE genotype (P < .001 to P = .006). Multiple binary logistic regression revealed that CSF levels of Aβ42 and APOE ε4 genotype were independent predictors of AD diagnosis. In cohort B, APOE ε4 carrier status did not influence CSF levels of

  17. Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression

    PubMed Central

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

    2017-01-01

    IMPORTANCE The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. OBJECTIVE To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer’s Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. MAIN OUTCOMES AND MEASURES Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. RESULTS Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134–1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923–1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061–1693] pg/mL) compared with control participants (1047 [809–1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = −4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = −54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = −1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and

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

    PubMed Central

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

    1980-01-01

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

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

    PubMed

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

    2016-09-01

    Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant-rate infusion study. Due to the dynamic nature of ICP, a 'snapshot' manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure-volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2016-07-01

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

  1. Endoscopic transpterygoidal repair of a large cranial defect with cerebrospinal fluid leak in a patient with extensive osteoradionecrosis of the skull base: case report and technical note.

    PubMed

    Brand, Y; Lim, E; Waran, V; Prepageran, N

    2015-12-01

    Endoscopic endonasal techniques have recently become the method of choice in dealing with cerebrospinal fluid leak involving the anterior cranial fossa. However, most surgeons prefer an intracranial approach when leaks involve the middle cranial fossa. This case report illustrates the possibilities of using endoscopic techniques for cerebrospinal fluid leaks involving the middle fossa. A 37-year-old male patient presented with multiple areas of cranial defect with cerebrospinal fluid leak due to osteoradionecrosis following radiation for nasopharyngeal carcinoma 4 years earlier. Clinical examination showed involvement of all cranial nerves except the IInd and XIth nerves on the left side. A prior attempt to repair the cerebrospinal fluid leak with craniotomy was not successful. This case demonstrates the successful endoscopic repair of a large cranial defect with cerebrospinal fluid leak.

  2. Spontaneous Intracranial Hypotension: A Review and Introduction of an Algorithm For Management.

    PubMed

    Davidson, Benjamin; Nassiri, Farshad; Mansouri, Alireza; Badhiwala, Jetan H; Witiw, Christopher D; Shamji, Mohammed F; Peng, Philip W; Farb, Richard I; Bernstein, Mark

    2017-05-01

    Spontaneous intracranial hypotension (SIH) is a condition of low cerebrospinal fluid volume and pressure caused by a leak of cerebrospinal fluid through a dural defect. Diagnosis and management can be difficult, often requiring coordination between multiple disciplines for myelography, blood patching, and possible surgical repair. Patients should be monitored closely, because they can deteriorate into a coma or even death. There are no widely accepted guidelines for the management of SIH. We review the existing SIH literature, illustrate management challenges via a case review, and propose an algorithm developed by neurosurgeons, radiologists, and anesthesiologists intended to simplify and streamline the management of SIH. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    SciTech Connect

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

    1990-01-01

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

  6. [Cerebrospinal fluid in clinical aspects of tuberculosis of the central nervous system].

    PubMed

    Shyshov, A S; Petrova, I S; Grishina, T P; Frolova, K S; Blank, I A; Inozemtseva, A B; Rusanova, S A; Ambrosy, O E

    2015-01-01

    To identify clinical features of tuberculosis of the meninges and central nervous system (TM) with detailed characterization of changes in the composition of cerebrospinal fluid (CSF) in the initial period of the disease. We analyzed the results of the examination of 42 patients, aged from 17 to 49 years, who were hospitalized in 2005-2014. Most of the patients were admitted in the hospital in early acute disease onset. Along with the description of inflectional and cerebral symptoms, meningeal signs, disorders of consciousness and focal symptoms, we presented cell count values, protein and glucose concentrations at initial examination of CSF as well as the results of additional examination and specific therapy issues. The importance of combining treatment standards and individualization of therapy of TM patients is emphasized.

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

    PubMed

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

    2001-08-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

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

    PubMed

    Walsted, A; Garbarsch, C; Michaels, L

    1994-11-01

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

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

    PubMed

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

    1987-03-01

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

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

    PubMed Central

    ÇOBAN, Arzu; SHUGAIV, Erkingül; TÜZÜN, Erdem

    2013-01-01

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

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

    SciTech Connect

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

    1984-02-01

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

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

    PubMed

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

    1984-02-01

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

  14. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells

    PubMed Central

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

    2011-01-01

    Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions. PMID:21382550

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

    PubMed

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

    2013-09-01

    Gorham-Stout syndrome is a rare disorder characterized by progressive osteolysis that leads to the disappearance of bone. Lymphvascular proliferation causes the local destruction of bony tissue. Owing to the low incidence of this syndrome, little is known about its etiology or treatment. We present an 11-year-old girl with Gorham-Stout syndrome that involved right petrous apex in temporal bone and upper clivus, which cause intracranial pressure increase and cerebrospinal fluid (CSF) leakage. The patient required surgical repair of CSF leakage by extradural middle fossa approach with temporal fascia flap. Combined treatment with interferon and propranolol prevented the progression of osteolysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2003-07-01

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

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

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2016-06-10

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

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

    PubMed

    Almeida, Sérgio Monteiro de

    2013-09-01

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

  20. Cerebrospinal fluid levels of alpha-tocopherol in patients with multiple sclerosis.

    PubMed

    Jiménez-Jiménez, F J; de Bustos, F; Molina, J A; de Andrés, C; Gasalla, T; Ortí-Pareja, M; Zurdo, M; Porta, J; Castellano-Millán, F; Arenas, J; Enríquez de Salamanca, R

    1998-06-12

    We compared cerebrospinal fluid (CSF) and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 36 patients with multiple sclerosis (MS) and 32 matched controls. The mean CSF vitamin E levels and the CSF/serum vitamin E ratio did not differ significantly between the two study groups. The serum levels of vitamin E and the serum vitamin E/cholesterol ratio were significantly lower in MS patients when compared with controls (P < 0.05 and P < 0.01, respectively). These values were not correlated with age, age at onset and duration of the disease in the patients group. These results suggest that CSF vitamin E concentrations are not a marker of activity of MS activity.

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

    PubMed

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

    2012-08-01

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

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

    PubMed

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

    2010-09-01

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

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

    PubMed Central

    Camargo, José Augusto; Bertolucci, Paulo Henrique Ferreira

    2015-01-01

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

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

    PubMed

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

    2005-08-01

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

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

    PubMed Central

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

    1994-01-01

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

  6. Increased resistin levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica.

    PubMed

    Qi, Yuan; Jia, Kun; Zhang, Da-Qi; Li, Ting; Li, Li-Min; Zhang, Lin-Jie; Wang, Jing; Gao, Chun-Li; Sun, Li-Sha; Shi, Fu-Dong; Yang, Li

    2016-05-01

    Resistin, which acts as a pro-inflammatory cytokine, has been implicated in the pathogenesis of several autoimmune diseases. However, the involvement of resistin in neuromyelitis optica (NMO), a severe inflammatory central nervous system disorder that targets the optic nerve and spinal cord, remains unclear. We measured serum and cerebrospinal fluid (CSF) resistin levels in patients with NMO and controls matched by age and sex. The link between resistin levels and clinical variables in NMO was subsequently assessed. The concentrations of serum and CSF resistin were significantly higher in patients with NMO than in controls, and decreased following treatment with methylprednisolone. High sensitivity C-reactive protein (hs-CRP) levels and annualized relapse rate positively correlated with resistin levels in patients with NMO. Resistin might be a useful biomarker of inflammation in NMO, and a potential target for the treatment of NMO. Copyright © 2016. Published by Elsevier B.V.

  7. HPLC-DAD determination of mepivacaine in cerebrospinal fluid from a fatal case.

    PubMed

    Nieddu, Maria; Boatto, Gianpiero; Serra, Domenico; Soro, Aldo; Lorenzoni, Salvatore; Lubinu, Francesco

    2007-09-01

    A fatal case involving mepivacaine-induced epidural anesthesia is described. The pathological findings were typical of cardiac shock from ischemic origin. Cerebrospinal fluid (CSF) was obtained several hours after death and mepivacaine was identified by gas chromatography-mass spectrometry (GC-MS). Its concentration was determined by high performance liquid chromatography with diode array detection (HPLC-DAD). Extraction from CSF was performed by deproteinization with acetonitrile. The mepivacaine concentration in the sample was 264 microg/mL. Concentrations of mepivacaine in CSF following epidural anesthesia are not reported in literature to our knowledge. This is the first reported case of death in which the mepivacaine concentration in CSF has been determined.

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

    PubMed Central

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

    2013-01-01

    Although universally recognized as the source of cerebrospinal fluid (CSF), the choroid plexus (ChP) has been one of the most understudied tissues in neuroscience. The reasons for this are multiple and varied, including historical perceptions about passive and permissive roles for the ChP, experimental issues, and lack of clinical salience. However, recent work on the ChP and instructive signals in the CSF have sparked new hypotheses about how the ChP and CSF provide unexpected means for regulating nervous system structure and function in health and disease, as well as new ChP-based therapeutic approaches using pluripotent stem cell technology. This minisymposium combines new and established investigators to capture some of the newfound excitement surrounding the ChP-CSF system. PMID:24198345

  9. Level of sFas/APO 1 in serum and cerebrospinal fluid in multiple sclerosis.

    PubMed

    Mahovic, Darija; Petravic, Damir; Petelin, Zeljka; Zurak, Niko; Horvat, Gordana; Hajnsek, Sanja

    2004-06-01

    The aim of the study was to measure sFas/APO 1 serum and cerebrospinal fluid (CSF) levels in patients with relapsing-remitting multiple sclerosis (MS) during relapses, as an index of inhibition of apoptosis of activated lymphocytes in eight patients with clinically definite multiple sclerosis, and 12 healthy controls. The level of serum and CSF sFas/APO 1 was determined by commercially available enzyme-linked immunosorbent assay (ELISA) kits. No significant differences were detected in the sFas/APO 1 serum level between patients and controls, but the levels in CSF was lower in the former. Our results suggest the possibility of Fas mediated apoptosis as a contributing factor in the pathogenesis of multiple sclerosis.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-04-27

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

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

    PubMed Central

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

    2001-01-01

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

 PMID:11124792

  14. Cerebrospinal fluid biomarkers of Alzheimer’s disease in cognitively healthy elderly

    PubMed Central

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

    2014-01-01

    Numerous studies have shown that Alzheimer’s Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinal fluid (CSF) biomarkers that reflect AD pathology: amyloid beta (Aß42), total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly. PMID:23747874

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

    PubMed

    Reiber, Hansotto

    2016-06-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

    Huynh, Rose Ann; Mohan, Chandra

    2017-01-01

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

  18. False-positive cerebrospinal fluid cryptococcus antigen in Libman-Sacks endocarditis.

    PubMed

    Isseh, Iyad N; Bourgi, Kassem; Nakhle, Asaad; Ali, Mahmoud; Zervos, Marcus J

    2016-12-01

    Cryptococcus meningoencephalitis is a serious opportunistic infection associated with high morbidity and mortality in immunocompromised hosts, particularly patients with advanced AIDS disease. The diagnosis is established through cerebrospinal fluid (CSF) cryptococcus antigen detection and cultures. Cryptococcus antigen testing is usually the initial test of choice due its high sensitivity and specificity along with the quick availability of the results. We hereby report a case of a false-positive CSF cryptococcus antigen assay in a patient with systemic lupus erythematosus presenting with acute confusion. While initial CSF evaluation revealed a positive cryptococcus antigen assay, the patient's symptoms were inconsistent with cryptococcus meningoencephalitis. A repeat CSF evaluation, done 3 days later, revealed a negative CSF cryptococcus antigen assay. Given the patient's active lupus disease and the elevated antinuclear antibody titers, we believe that the initial positive result was a false positive caused by interference from autoantibodies.

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

    PubMed

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

    2001-09-01

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

  20. 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.

  1. Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis.

    PubMed

    Arbeille, Elise; Reynaud, Florie; Sanyas, Isabelle; Bozon, Muriel; Kindbeiter, Karine; Causeret, Frédéric; Pierani, Alessandra; Falk, Julien; Moret, Frédéric; Castellani, Valérie

    2015-02-27

    The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones.

  2. Three-dimensional computational prediction of cerebrospinal fluid flow in the human brain.

    PubMed

    Sweetman, Brian; Xenos, Michalis; Zitella, Laura; Linninger, Andreas A

    2011-02-01

    A three-dimensional model of the human cerebrospinal fluid (CSF) spaces is presented. Patient-specific brain geometries were reconstructed from magnetic resonance images. The model was validated by comparing the predicted flow rates with Cine phase-contrast MRI measurements. The model predicts the complex CSF flow patterns and pressures in the ventricular system and subarachnoid space of a normal subject. The predicted maximum rostral to caudal CSF flow in the pontine cistern precedes the maximum rostral to caudal flow in the ventricles by about 10% of the cardiac cycle. This prediction is in excellent agreement with the subject-specific flow data. The computational results quantify normal intracranial dynamics and provide a basis for analyzing diseased intracranial dynamics. Published by Elsevier Ltd.

  3. Three-dimensional computational prediction of cerebrospinal fluid flow in the human brain

    PubMed Central

    Sweetman, Brian; Xenos, Michalis; Zitella, Laura; Linninger, Andreas A.

    2011-01-01

    A three-dimensional model of the human cerebrospinal fluid (CSF) spaces is presented. Patient-specific brain geometries were reconstructed from magnetic resonance images. The model was validated by comparing the predicted flow rates with Cine phase-contrast MRI measurements. The model predicts the complex CSF flow patterns and pressures in the ventricular system and subarachnoid space of a normal subject. The predicted maximum rostral to caudal CSF flow in the pontine cistern precedes the maximum rostral to caudal flow in the ventricles by about 10% of the cardiac cycle. This prediction is in excellent agreement with the subject-specific flow data. The computational results quantify normal intracranial dynamics and provide a basis for analyzing diseased intracranial dynamics. PMID:21215965

  4. Cerebrospinal fluid Coccidioides antigen testing in the diagnosis and management of central nervous system coccidioidomycosis.

    PubMed

    Bamberger, David M; Pepito, Brian S; Proia, Laurie A; Ostrosky-Zeichner, Luis; Ashraf, Madiha; Marty, Francisco; Scully, Eileen; Wheat, L Joseph

    2015-10-01

    The goal of this study was to report on the potential utility of cerebrospinal fluid (CSF) Coccidioides antigen testing in the diagnosis and management of Coccidioides meningitis. We retrospectively reviewed medical records of seven patients with Coccidioides meningitis who had Coccidioides antigen tests performed on CSF. In two severely immunocompromised patients, CSF Coccidioides antigen testing was helpful in the diagnosis when other testing modalities were negative. Coccidioides antigen testing was also useful in the management of patients who had progression of disease due to non-adherence, development of resistance, failure of therapy and the presence of vasculitis. Changing antigen levels helped identify disease complications in three patients that led to alterations in therapy or management. On the basis of our review of these seven patients with Coccidioides meningitis, we concluded that the Coccidioides antigen test contributed to the diagnosis and management of patients with Coccidioides meningitis. © 2015 Blackwell Verlag GmbH.

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

    PubMed Central

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

    1986-01-01

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

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

    PubMed

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

    1998-06-12

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

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

    PubMed

    Guyer, Richard A; Turner, Justin H

    2015-01-01

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

  8. Slc20a2 is critical for maintaining a physiologic inorganic phosphate level in cerebrospinal fluid.

    PubMed

    Jensen, Nina; Autzen, Jacob Kwasi; Pedersen, Lene

    2016-04-01

    Mutations in the SLC20A2-gene encoding the inorganic phosphate (Pi) transporter PiT2 can explain approximately 40% of the familial cases of the rare neurodegenerative disorder primary familial brain calcification (Fahr's disease). The disease characteristic, cerebrovascular-associated calcifications, is also present in Slc20a2-knockout (KO) mice. Little is known about the specific role(s) of PiT2 in the brain. Recent in vitro studies, however, suggest a role in regulation of the [Pi] in cerebrospinal fluid (CSF). We here show that Slc20a2-KO mice indeed have a high CSF [Pi] in agreement with a role of PiT2 in Pi export from the CSF. The implications in relation to disease mechanism are discussed.

  9. A Window into the Heterogeneity of Human Cerebrospinal Fluid Aβ Peptides

    PubMed Central

    Ghidoni, Roberta; Paterlini, Anna; Albertini, Valentina; Stoppani, Elena; Binetti, Giuliano; Fuxe, Kjell; Benussi, Luisa; Agnati, Luigi F.

    2011-01-01

    The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (Aβ) peptides leading to the formation of neurotoxic brain Aβ assemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF Aβ peptides. Specifically, we focused our attention on the heterogeneity of the CSF Aβ world discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating Aβ assemblies, and (3) communication modes for Aβ peptides and their microenvironment targets. Finally, we suggest that Aβ peptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function. PMID:21876644

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

    PubMed Central

    Reyes, Camilo; Solares, C. Arturo

    2015-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2017-06-01

    Fibroblast growth factor 21 (FGF21) is an important metabolic regulator of glucose homeostasis and lipid metabolism. Recently, FGF21 has been shown to play a robust neuroprotective role and act as a mediator of the effects of mood stabilizers. In the present study, we measured the concentration of FGF21 in human cerebrospinal fluid (CSF) and investigated the relationship of FGF21 levels with depression and anxiety emotions. Sixty-seven Chinese volunteers were recruited from Beijing Jishuitan Hospital. A significant negative association was found between CSF FGF21 levels and Beck Depression Inventory (BDI) scores in male subjects. Our findings provide evidence of the role of FGF21 in mood regulation. Copyright © 2017. Published by Elsevier B.V.

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

    PubMed

    Grevel, V; Machus, B; Steeb, C

    1992-08-01

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

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

    PubMed

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

    1997-02-01

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

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

    PubMed

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

    2015-01-01

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

  17. 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.

  18. 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

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

    PubMed

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

    2005-02-01

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

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2015-08-28

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

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

    PubMed

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

    2014-06-01

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

  5. 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).

  6. [External lumbar drainage with volumetric continuing infusion pump in patients with cerebrospinal fluid leak. A case series].

    PubMed

    Manso Melgosa, Ana Belén; García Gutiérrez, Helena; Fernández Porras, Mónica; Castrillo Manero, Ana Berta; Pérez Marijuán, Belén

    To describe the incidence and complications arising in a number of cases of patients with cerebrospinal fluid leak treated by external lumbar drainage with infusion pump (IP) volumetric continuous from 2001 to 2014. Quantify cerebrospinal fluid leak closed by lumbar drainage with IP. Retrospective descriptive case series study. patients undergoing transsphenoidal pituitary surgery, Chiari surgery and laminectomy, that developed postoperative cerebrospinal fluid leak treated with continuous external lumbar drainage by IP. age, sex, type of intervention, variables related to the practice of the pump and complications. Average and medians were calculated for quantitative variables, frequencies and percentages for qualitative. Sample: 11 subjects. Incidence in running IP: disconnection, occlusion and acoustic alarm activation. Most frequently complication is headache; a case of pneumocephalus. The small number of subjects and the heterogeneity of these do not allow for comparison or establishing associations between variables. The resolution of the cerebrospinal fluid leak with continuous IP is lower in this study than others, and may be influenced by the small number of subjects. It should be noted the frequent activation of the pump alarm for no apparent cause. Protocol would be developed for preparing the IP team to reduce the acoustic alarm activation, and would make a prospective multicenter study. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. Cerebrospinal fluid total protein cannot reliably distinguish true subarachnoid haemorrhage from other causes of raised cerebrospinal fluid net bilirubin and net oxyhaemoglobin absorbances.

    PubMed

    Birch, Katherine; Burrows, Gillian; Cruickshank, Anne; Egner, William; Holbrook, Ian; Lewis, Emma; McNeilly, Jane; Patel, Dina; Worthington, Viki

    2014-11-01

    In cerebrospinal fluid (CSF) spectrophotometry, if the net bilirubin absorbance (NBA) and net oxyhaemoglobin absorbance (NOA) are both raised with a visible oxyhaemoglobin peak, the revised national guidelines for analysis of CSF bilirubin advise interpreting the results as 'Consistent with subarachnoid haemorrhage (SAH)' regardless of the CSF total protein concentration of the specimen. We wanted to study the range of CSF total protein concentrations found in confirmed SAH to establish if the CSF total protein value can give further guidance on the likelihood of SAH. Consecutive cases from five different hospital sites were included if the CSF NBA was greater than 0.007 AU and the NOA was greater than 0.02 AU with a visible oxyhaemoglobin peak. For the cases identified, the laboratory information management system and patient records were interrogated to identify the total protein concentration of the CSF specimen and whether SAH had ultimately been confirmed or excluded by other methods and supporting evidence. Results from 132 patients were included. The CSF total protein range in confirmed SAH was 0.23-3.08 g/L with a median concentration of 0.7 g/L (n = 51). In the SAH excluded group, the CSF total protein range was 0.43-29 g/L with a median concentration of 1.9 g/L (n = 81). Although confirmed SAH was not associated with the very highest concentrations of CSF total protein, a definite CSF protein cut-off concentration above which SAH could reliably be excluded cannot be recommended. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2010-11-01

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

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

    PubMed Central

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

    2009-01-01

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

  12. Evaluation of Spontaneous Spinal Cerebrospinal Fluid Leaks Disease by Computerized Image Processing.

    PubMed

    Yıldırım, Mustafa S; Kara, Sadık; Albayram, Mehmet S; Okkesim, Şükrü

    2016-05-17

    Spontaneous Spinal Cerebrospinal Fluid Leaks (SSCFL) is a disease based on tears on the dura mater. Due to widespread symptoms and low frequency of the disease, diagnosis is problematic. Diagnostic lumbar puncture is commonly used for diagnosing SSCFL, though it is invasive and may cause pain, inflammation or new leakages. T2-weighted MR imaging is also used for diagnosis; however, the literature on T2-weighted MRI states that findings for diagnosis of SSCFL could be erroneous when differentiating the diseased and control. One another technique for diagnosis is CT-myelography, but this has been suggested to be less successful than T2-weighted MRI and it needs an initial lumbar puncture. This study aimed to develop an objective, computerized numerical analysis method using noninvasive routine Magnetic Resonance Images that can be used in the evaluation and diagnosis of SSCFL disease. Brain boundaries were automatically detected using methods of mathematical morphology, and a distance transform was employed. According to normalized distances, average densities of certain sites were proportioned and a numerical criterion related to cerebrospinal fluid distribution was calculated. The developed method was able to differentiate between 14 patients and 14 control subjects significantly with p = 0.0088 and d = 0.958. Also, the pre and post-treatment MRI of four patients was obtained and analyzed. The results were differentiated statistically (p = 0.0320, d = 0.853). An original, noninvasive and objective diagnostic test based on computerized image processing has been developed for evaluation of SSCFL. To our knowledge, this is the first computerized image processing method for evaluation of the disease. Discrimination between patients and controls shows the validity of the method. Also, post-treatment changes observed in four patients support this verdict.

  13. Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis.

    PubMed

    Møllgaard, M; Degn, M; Sellebjerg, F; Frederiksen, J L; Modvig, S

    2016-05-01

    The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins is yet to be established. Our objective was to investigate the potential of chitinase 3-like 2 (CHI3L2) and chitotriosidase as prognostic biomarkers in optic neuritis (ON) as the first demyelinating episode and to evaluate the ability of CHI3L2 to predict long-term MS risk and disability. In a prospective cohort of 73 patients with ON as a first demyelinating episode and 26 age-matched healthy controls levels of CHI3L2 and chitotriosidase in CSF were explored by enzyme-linked immunosorbent assay. Associations with magnetic resonance imaging white matter lesions, CSF oligoclonal bands, immunoglobulin G index and leukocyte count were investigated. Long-term MS risk and disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite components) were examined in a retrospective cohort of 78 patients with ON as the first demyelinating episode (mean follow-up 14 years). The predictive ability of CHI3L2 was compared with CHI3L1. Cerebrospinal fluid levels of CHI3L2 and chitotriosidase were significantly elevated in patients with ON and were associated with MS risk measures. CHI3L2 levels predicted MS development after ON (hazard ratio 1.95, P = 0.00039, Cox regression) and cognitive impairment by the Paced Auditory Serial Addition Test (P = 0.0357, linear regression) at follow-up. In a multivariate analysis of MS risk, CHI3L2 performed better than CHI3L1. CHI3L2 and chitotriosidase are promising biomarkers in patients with a first demyelinating episode. Our findings thus support a role for these proteins as biomarkers in early MS. © 2016 EAN.

  14. STUDIES ON THE TRANSFERRINS OF ADULT SERUM, CORD SERUM, AND CEREBROSPINAL FLUID

    PubMed Central

    Parker, W. Carey; Bearn, Alexander G.

    1962-01-01

    Nine of the twelve known variants of human transferrin have been resolved by the action of neuraminidase into stepwise patterns of four additional slower moving components whose relative intensities depended upon the concentration of enzyme. These components appeared to represent the stepwise removal of the four sialic acid residues from the transferrin molecule, and at large enzyme concentrations, almost all of the transferrin was reduced to the position of the slowest moving component. In contrast, the electrophoretic mobilities of haptoglobin, ceruloplasmin, and α2-macroglobulin showed a gradual decrease with increasing neuraminidase concentration. The transferrins of chimpanzees, rhesus and cynomolgus monkeys, and cattle were resolved by neuraminidase into two slower moving components. These experiments suggested that the primate and cattle transferrins contained only two sialic acid residues accessible to the enzyme. Transferrins C, B2, and D1 and a cynomolgus monkey transferrin were purified from serum by starch block electrophoresis and cellulose chromatography. Ultracentrifugal analysis could detect no difference in sedimentation rate between transferrin C, the primate transferrin, and neuraminidase-treated transferrin C. The human transferrins showed no variation in amino acid composition, but the cynomolgus transferrin was approximately 20 per cent higher in serine content and 50 per cent lower in glucosamine than human transferrin C. Reactions of antigenic identity were obtained among five human transferrin variants but a reaction of only partial identity was obtained between transferrin C and the cynomolgus transferrin. The transferrin pattern of cord blood showed a prominent band in the position of transferrin C, accompanied by four faint slower moving bands which coincided with the four transferrin components produced by the action of neuraminidase on transferrin C. The transferrin pattern of cerebrospinal fluid in individuals homozygous for serum

  15. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.

    PubMed

    Galasko, Douglas R; Peskind, Elaine; Clark, Christopher M; Quinn, Joseph F; Ringman, John M; Jicha, Gregory A; Cotman, Carl; Cottrell, Barbara; Montine, Thomas J; Thomas, Ronald G; Aisen, Paul

    2012-07-01

    To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers. Double-blind, placebo-controlled clinical trial. Academic medical centers. Subjects with mild to moderate Alzheimer disease. Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo. Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale). Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups. Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted. clinicaltrials.gov Identifier: NCT00117403.

  16. 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

  17. 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

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

    PubMed

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  20. Three-dimensional computational modeling of subject-specific cerebrospinal fluid flow in the subarachnoid space.

    PubMed

    Gupta, Sumeet; Soellinger, Michaela; Boesiger, Peter; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2009-02-01

    This study aims at investigating three-dimensional subject-specific cerebrospinal fluid (CSF) dynamics in the inferior cranial space, the superior spinal subarachnoid space (SAS), and the fourth cerebral ventricle using a combination of a finite-volume computational fluid dynamics (CFD) approach and magnetic resonance imaging (MRI) experiments. An anatomically accurate 3D model of the entire SAS of a healthy volunteer was reconstructed from high resolution T2 weighted MRI data. Subject-specific pulsatile velocity boundary conditions were imposed at planes in the pontine cistern, cerebellomedullary cistern, and in the spinal subarachnoid space. Velocimetric MRI was used to measure the velocity field at these boundaries. A constant pressure boundary condition was imposed at the interface between the aqueduct of Sylvius and the fourth ventricle. The morphology of the SAS with its complex trabecula structures was taken into account through a novel porous media model with anisotropic permeability. The governing equations were solved using finite-volume CFD. We observed a total pressure variation from -42 Pa to 40 Pa within one cardiac cycle in the investigated domain. Maximum CSF velocities of about 15 cms occurred in the inferior section of the aqueduct, 14 cms in the left foramen of Luschka, and 9 cms in the foramen of Magendie. Flow velocities in the right foramen of Luschka were found to be significantly lower than in the left, indicating three-dimensional brain asymmetries. The flow in the cerebellomedullary cistern was found to be relatively diffusive with a peak Reynolds number (Re)=72, while the flow in the pontine cistern was primarily convective with a peak Re=386. The net volumetric flow rate in the spinal canal was found to be negligible despite CSF oscillation with substantial amplitude with a maximum volumetric flow rate of 109 mlmin. The observed transient flow patterns indicate a compliant behavior of the cranial subarachnoid space. Still, the estimated

  1. Coconut Model for Learning First Steps of Craniotomy Techniques and Cerebrospinal Fluid Leak Avoidance.

    PubMed

    Drummond-Braga, Bernardo; Peleja, Sebastião Berquó; Macedo, Guaracy; Drummond, Carlos Roberto S A; Costa, Pollyana H V; Garcia-Zapata, Marco T; Oliveira, Marcelo Magaldi

    2016-12-01

    Neurosurgery simulation has gained attention recently due to changes in the medical system. First-year neurosurgical residents in low-income countries usually perform their first craniotomy on a real subject. Development of high-fidelity, cheap, and largely available simulators is a challenge in residency training. An original model for the first steps of craniotomy with cerebrospinal fluid leak avoidance practice using a coconut is described. The coconut is a drupe from Cocos nucifera L. (coconut tree). The green coconut has 4 layers, and some similarity can be seen between these layers and the human skull. The materials used in the simulation are the same as those used in the operating room. The coconut is placed on the head holder support with the face up. The burr holes are made until endocarp is reached. The mesocarp is dissected, and the conductor is passed from one hole to the other with the Gigli saw. The hook handle for the wire saw is positioned, and the mesocarp and endocarp are cut. After sawing the 4 margins, mesocarp is detached from endocarp. Four burr holes are made from endocarp to endosperm. Careful dissection of the endosperm is done, avoiding liquid albumen leak. The Gigli saw is passed through the trephine holes. Hooks are placed, and the endocarp is cut. After cutting the 4 margins, it is dissected from the endosperm and removed. The main goal of the procedure is to remove the endocarp without fluid leakage. The coconut model for learning the first steps of craniotomy and cerebrospinal fluid leak avoidance has some limitations. It is more realistic while trying to remove the endocarp without damage to the endosperm. It is also cheap and can be widely used in low-income countries. However, the coconut does not have anatomic landmarks. The mesocarp makes the model less realistic because it has fibers that make the procedure more difficult and different from a real craniotomy. The model has a potential pedagogic neurosurgical application for

  2. Separation of beta2-transferrin by denaturing gel electrophoresis to detect cerebrospinal fluid in ear and nasal fluids.

    PubMed

    Görögh, Tibor; Rudolph, Pierre; Meyer, Jens Eduard; Werner, Jochen A; Lippert, Burkard M; Maune, Steffen

    2005-09-01

    Cerebrospinal fluid (CSF) leakage is a critical condition with a substantial risk of meningitis. We investigated the use of transferrin isoform analysis as a diagnostic marker for detection of CSF leakage in fluid samples. We analyzed 241 samples from patients with CSF leakage, most commonly presenting as otorrhea or rhinorrhea, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with subsequent Western blotting and immunostaining for transferrin. Tears, saliva, nasal fluid, and ear secretions (20 samples each) were analyzed in parallel, and normal human serum served as a control in each experiment. We compared the minimum volume of added CSF that could be detected in secretions by our assay with the minimum volume detected by the prostaglandin-D synthase (beta-trace) test. CSF was admixed with blood in different proportions to determine the influence of blood contamination on the transferrin pattern. In all CSF samples, beta1- and beta2-transferrin were present in nearly equal amounts. In tears and ear secretions, beta2-transferrin migrated in the gel in the same manner as in CSF, but its concentration was noticeably lower than that of beta1-transferrin, a difference that allowed a clear distinction from the transferrin pattern of CSF. In saliva, both transferrin isoforms were also present but could be distinguished from those of other fluids by electrophoretic migration pattern rather than relative concentrations. With the beta-trace test, a minimum of 5 microL of CSF was needed for detection, whereas our beta2-transferrin assay yielded a signal of comparable intensity with a minimum of 2 microL of CSF. Analysis of the transferrin microheterogeneity pattern by SDS-PAGE for the identification of CSF leakage is a highly sensitive and specific method that merits consideration as a routine technique.

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

    PubMed Central

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

    2017-01-01

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

  4. 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.

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

    PubMed

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

    2014-05-06

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    David, Monique Antoinette; Tayebi, Mourad

    2014-01-01

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

  8. Predictive value of the leukocyte esterase test for the detection of pleocytosis in cerebrospinal fluid.

    PubMed

    Shokouhi, Shervin; Darazam, Ilad Alavi; Karamipour, Mehdi; Ahmadi, HasanAli; Sajadi, Mohammad M

    2017-03-17

    Rapid and accurate diagnostic tests for patients with suspected bacterial meningitis is crucial to prevent subsequent mortality and morbidity. We carried out this study to determine diagnostic value of the rapid leukocyte esterase (LE) strip test to identify PMN pleocytosis in cerebral spinal fluid. A total of 126 patients with suspected meningitis were enrolled in this prospective study. Microscopic examination (cell count and differential) and leukocyte esterase (LE) rapid strip test was performed on cerebrospinal fluid (CSF) samples. Sensitivity, specificity, positive predictive value and negative predictive value of the LE test were determined. The receiver operating characteristic (ROC) was used to calculate the best cut-point values. Fifty and two (41%) of patients had pleocytosis in the CSF, while 48 (38%) patients had a positive result the using rapid strip test. The diagnostic accuracy of this test for pleocytosis translated to a sensitivity of 85% and a specificity of 86%, with an area under the curve of 0.88. The rapid LE strip test could be considered an additional test in the patient bedside for diagnosis of pleocytosis in CSF. It is a feasible test in resource-limited settings. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed Central

    Simon, Matthew J.; Iliff, Jeffrey J.

    2015-01-01

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

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

    PubMed

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

    2017-02-15

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

  11. Impedimetric nanostructured genosensor for detection of schistosomiasis in cerebrospinal fluid and serum samples.

    PubMed

    Santos, Giselle S; Andrade, Cesar A S; Bruscky, Igor S; Wanderley, Leandro B; Melo, Fabio L; Oliveira, Maria D L

    2017-04-15

    Schistosomiasis is a neglected disease closely related to the low levels of social development and a serious public health problem. In this work, we performed an electrochemical detection of Schistosoma mansoni DNA with a self-assembled monolayer of mercaptobenzoic acid (MBA) immobilizing nanostructures composed of gold nanoparticles (AuNPs) and magnetite nanoparticles (Fe3O4_NPs). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to monitor the hybridization process. MBA-Fe3O4_NPs-AuNPs-DNAprobe system reveals an effective electrochemical response indicating the surface modification. The proposed biosystem was capable to recognize specific nucleotide sequence of S. mansoni present in cerebrospinal fluid (CFS) and serum samples at different genome DNA concentrations. The biorecognition resulted in an increase in the electron transfer resistance and a decrease of the current peaks at higher DNA concentrations during electrochemical measurements. The developed platform showed a DNA detection limit of 0.781 and 0.685pgμL(-1) for serum and CFS, respectively. Therefore, the obtained biosensor can be considered as a useful tool for specific detection of S. mansoni at low concentrations in various biological fluids.

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Khan, Tapan K; Alkon, Daniel L

    2015-01-01

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

  14. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function.

    PubMed

    Kallestrup, M; Møller, H J; Tankisi, H; Andersen, H

    2015-01-01

    To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed using an enzyme-linked immunosorbent assay. Soluble CD163 levels were significantly higher in the cerebrospinal fluid and serum of the participants with Type 2 diabetes compared with the control participants [cerebrospinal fluid: median (range) 107 (70-190) vs 84 (54-115) μg/l, P < 0.01 and serum: 2305 (920-7060) vs 1420 (780-2740) μg/l, P < 0.01). Cerebrospinal fluid soluble CD163 was positively related to impaired peripheral nerve conduction (nerve conduction study rank score: r = 0.42; P = 0.0497) and there was a trend for higher levels of soluble CD163 in the cerebrospinal fluid and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) μg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral nerve function. Higher levels of soluble CD163 in people with diabetic polyneuropathy suggest that inflammation plays a role in the development of neural impairment. The relationship between cerebrospinal fluid soluble CD163 level and peripheral nerve conduction indicates that soluble CD163 may be a potential biomarker for the severity of diabetic polyneuropathy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  15. New understanding of the role of cerebrospinal fluid: offsetting of arterial and brain pulsation and self-dissipation of cerebrospinal fluid pulsatile flow energy.

    PubMed

    Min, Kyung Jay; Yoon, Soo Han; Kang, Jae-Kyu

    2011-06-01

    Many theories have been postulated to date regarding the mechanisms involved in the absorption of the intracranial arterial blood flow energy in the intracranial space, but it is as yet nor clearly defined. The blood flow energy that is transmitted from the heart formulates the cerebrospinal fluid (CSF) pulsatile flow, and is known to constitute the major energy of the CSF flow, while the bulk flow carries only small energy. The intracranial space that is enclosed in a solid cranium and is an isolate system as in the Monroe-Kellie doctrine, and the authors propose to re-analyze the Monroe-Kellie doctrine concept in terms of energy transfer and dissipation of the Windkessel effect. We propose that the large blood flow energy that initiates in the heart is transferred in order of precedence to the arteries, arterioles, brain parenchyma, and finally to CSF within the cranium, in which the energy is confined and unable to be transferred, so that the final transfer of energy to the CSF pulsatile flow is self-dissipated in terms of direction and chronology in CSF pulsatile flow. In order for the CSF pulsatile flow that is transferred from arterial blood flow energy to be dissipated in the intracranial space, this cannot be explained with bulk flow energy in any perspective, since the pulsatile flow kinetic energy is greater than the bulk flow kinetic energy by at least a 100-fold. The pulsatile flow energy within the closed intracranial space cannot be transferred and is confined, as postulated by the Monroe-Kellie doctrine, and therefore the authors propound that the pulsatile flow dissipates by itself. The dissipation of the CSF pulsatile flow kinetic energy will be in all directions in a diffuse and random manner, and is offset by the CSF flow energy vector due to the CSF mixing process. Such energy dissipation will lead to maintenance of low CSF flow energy, which will result in maintaining low intracranial pressure (ICP), and sufficient brain perfusion. It is our

  16. Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children.

    PubMed

    Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

    2017-01-01

    To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone. Avaliar o papel da pesquisa de enterovírus no líquido cefalorraquidiano em comparação com o Escore de Meningite Bacteriana em crianças com meningite. Coorte retrospectiva, realizada pela análise de prontuários, incluindo pacientes pediátricos, com diagnóstico de meningite e atendidos em um hospital privado e terciário, localizado em São Paulo, entre 2011 e 2014. Foram excluídos os pacientes com doença crítica, púrpura, deriva

  17. Adrenomedullin Prevents Sex-Dependent Impairment of Autoregulation during Hypotension after Piglet Brain Injury through Inhibition of ERK MAPK Upregulation

    PubMed Central

    Kiessling, J. Willis; Bdeir, Khalil; Kofke, W. Andrew; Vavilala, Monica S.

    2010-01-01

    Abstract Cerebrospinal fluid (CSF) adrenomedullin (ADM) levels are increased in female, but remain unchanged in male, piglets after fluid percussion injury (FPI) of the brain. Subthreshold vascular concentrations of ADM restore impaired hypotensive pial artery dilation after FPI more in males than females. Extracellular signal-related kinase (ERK) mitogen-activated protein kinase (MAPK) is upregulated and contributes to reductions in cerebral blood flow (CBF) after FPI. We hypothesized that ADM prevents sex-dependent impairment of autoregulation during hypotension after FPI through inhibition of ERK MAPK upregulation. FPI increased ERK MAPK more in males than in females. CBF was unchanged during hypotension in sham animals, was reduced more in males than in females after FPI during normotension, and was further reduced in males than in females during hypotension and after FPI. ADM and the ERK MAPK antagonist U 0126 prevented reductions in CBF during hypotension and FPI more in males than in females. Transcranial Doppler (TCD) blood flow velocity was unchanged during hypotension in sham animals, was decreased during hypotension and FPI in male but not in female pigs, and was ameliorated by ADM. Intracranial pressure (ICP) was increased after FPI more in male than in female animals. ADM blunted elevated ICP during FPI and hypotension in males, but not in females. ADM prevented reductions in cerebral perfusion pressure (CPP) during FPI and hypotension in males but not in females. The calculated autoregulatory index was unchanged during hypotension in sham animals, but was reduced more in males than females during hypotension and FPI. ADM prevented reductions in autoregulation during hypotension and FPI more in males than females. These data indicate that ADM prevented loss of cerebral autoregulation after FPI in a sex-dependent and ERK MAPK-dependent manner. PMID:20170313

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

    PubMed Central

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

    2016-01-01

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

  19. Early experience with automatic pressure-controlled cerebrospinal fluid drainage during thoracic endovascular aortic repair.

    PubMed

    Kotelis, Drosos; Bianchini, Claudio; Kovacs, Bence; Müller, Thomas; Bischoff, Moritz; Böckler, Dittmar

    2015-06-01

    To report initial experience with automatic pressure-controlled cerebrospinal fluid drainage (CSFD) during thoracic endovascular aortic repair (TEVAR). A prospective nonrandomized study enrolled 30 consecutive patients (median age 68 years, range 42-89; 18 men) who underwent TEVAR between March 2012 and July 2013 and were considered to be at high risk for postoperative spinal cord ischemia (SCI), fulfilling 2 of the following criteria: stent-graft length >20 cm, left subclavian artery coverage, and previous infrarenal aortic repair. All patients received perioperative CSFD via the LiquoGuard system. The protocol aimed for a CSF pressure of 10 mm Hg and duration of CSFD of 3 or 7 days in asymptomatic or symptomatic patients, respectively. Muscle strength of the lower extremities was assessed with the Oxford muscle strength grading scale. Completion of the CSFD protocol was achieved in 26 (87%) of 30 patients. CSFD was prematurely stopped due to catheter dislocation in 1 patient and bloody spinal fluid in 3 patients. CSFD was performed for a median of 3 days (range 1-7). Median total CSFD volume was 714 mL (range 13-2369), with a median 192 mL drained per 24 hours. The SCI rate was 3% (1/30). CSFD-related complications were observed in 33% of the patients: 1 fatal intracranial hemorrhage, 3 bloody spinal fluid episodes, 3 persistent CSF leaks requiring epidural blood patch, and 3 post lumbar puncture headaches. Mortality during a median follow-up of 16 months (range 10-25) was 3% (1/30). Prophylactic CSFD was associated with a low SCI rate in a high-risk patient collective undergoing TEVAR. Monitoring and drainage by an automatic modus was feasible, reproducible, and reliable but associated with relevant drainage-associated complications. © The Author(s) 2015.

  20. Effect of Cognitive Reserve on Age-Related Changes in Cerebrospinal Fluid Biomarkers of Alzheimer Disease.

    PubMed

    Almeida, Rodrigo P; Schultz, Stephanie A; Austin, Benjamin P; Boots, Elizabeth A; Dowling, N Maritza; Gleason, Carey E; Bendlin, Barbara B; Sager, Mark A; Hermann, Bruce P; Zetterberg, Henrik; Carlsson, Cynthia M; Johnson, Sterling C; Asthana, Sanjay; Okonkwo, Ozioma C

    2015-06-01

    Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. To investigate whether cognitive reserve (CR) modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. A cross-sectional cohort of 268 individuals (211 in a cognitively normal group and 57 in a cognitively impaired group) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. In addition, we computed t-tau/Aβ42 and p-tau/Aβ42 ratios. Cognitive reserve was indexed by years of education, with 16 or more years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by CR. The study dates were March 5, 2010, to February 13, 2013. Cerebrospinal fluid levels of Aβ42, t-tau, p-tau, t-tau/Aβ42, and p-tau/Aβ42. There were significant age × CR interactions for CSF t-tau (β [SE] = -6.72 [2.84], P = .02), p-tau (β [SE] = -0.71 [0.27], P = .01), t-tau/Aβ42 (β [SE] = -0.02 [0.01], P = .02), and p-tau/Aβ42 (β [SE] = -0.002 [0.001], P = .004). With advancing age, individuals with high CR exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low CR. This attenuation of age effects by CR tended to be more pronounced in the cognitively impaired group compared with the cognitively normal group. There was evidence of a dose-response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling. In a sample composed of a cognitively normal group

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2012-03-01

    Alterations of the intracellular ubiquitin-proteasome pathway are found in neurodegenerative and inflammatory disorders of the central nervous system, as well as in its malignancies. Inhibitory substrates of the proteasomes represent promising approaches to control autoimmune inflammations and induction of apoptosis in cancer cells. Extracellular circulating proteasomes are positively correlated to outcome prognosis in hematogenic neoplasias and the outcome in critically ill patients. Previously, we reported raised levels of proteolytic active 20S proteasomes in the extracellular alveolar space in patients with acute respiratory distress syndrome (ARDS). For the cerebrospinal fluid, we assumed that extracellular circulati