|
| ||
|
|
||
CSF
Kinds of CSF Terms modified by CSF Selected AbstractsDetection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene with particular reference to neonatal septicemiaACTA PAEDIATRICA, Issue 2 2001S Shang Aim: The clinical diagnosis of sepsis is difficult, particularly in neonates. It is necessary to develop a rapid and reliable method for detecting bacteria in blood and cerebrospinal fluid (CSF) Polymerase chain reaction (PCR) and reverse hybridization of the 16S rRNA gene would permit fast and sensitive determination of the presence of bacteria and differentiate gram-positive bacteria from gram-negative ones in clinical specimens. Methods: We developed a pair of primers according to the gene encoding 16SrRNA found in all bacteria. DNA fragments from different bacterial species and from clinical samples were detected with PCR, and with reverse hybridization using a universal bacterial probe, a gram-positive probe and a gram-negative probe. Results: A 371 bp DNA fragment was amplified from 20 different bacterial species. No signal was observed when human DNA and viruses were used as templates. The sensitivity could be improved to 10T -12 g. All 26 culture-positive clinical samples (22 blood samples and 4 CSF samples) were positive with PCR. The gram-negative and gram-positive probes hybridized to clinical samples and to known bacterial controls, as predicted by Gram's stain characteristics. Conclusions: Our results suggest that the method of PCR and reverse hybridization is rapid, sensitive and specific in detecting bacterial infections. This finding may be significant in the clinical diagnosis of sepsis in neonates. [source] Etiologic spectrum and pattern of antimicrobial drug susceptibility in bacterial meningitis in Sokoto, NigeriaACTA PAEDIATRICA, Issue 8 2000FE EmeleArticle first published online: 2 JAN 200 Etiologic agents of meningitis were prospectively investigated among patients admitted to Usman Danfodio University Teaching Hospital, Sokoto. Of 1097 cerebrospinal fluid (CSF) samples submitted to the microbiology laboratory from various wards of the hospital, 289 (26%) were microscopically, culturally and/or serologically proven to be bacterial meningitis. The etiologic spectrum was as follows: Neisseria meningitidis (61%), Streptococcus pneumoniae (18%), Haemophilus influenzae (10%), Staphylococcus aureus (6%), Coliform bacilli (3%), Escherichia coli (0.7%), Mycobacterium tuberculosis (0.7%), Listeria monocytogenes (0.4%), Flavobacterium meningosepticum (0.4%) and Pseudomonas putrifasciens (0.4%). Bacterial meningitis was most prevalent (195 or 68%) among children aged 1-9 y, while adults and neonates were least affected. Coliform bacilli caused five of eight neonatal cases. Males were more frequently affected than females (x2=12.50;p < 0.05). Culture and microscopy were comparatively less efficient than the search for bacterial antigens, especially in the diagnosis of Haemophilus meningitis. Antimicrobial susceptibility of N. meningitidis to ampicillin and benzyl penicillin reduced progressively over the years (F = 406.98;p < 0.001). Nineteen (11%) of the isolates (5 Meningococci, 7 Staph. aureus, 1 Haem. influenza and 6 others) showed simultaneous resistance to chloramphenicol, ampicillin and benzyl penicillin. [source] Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autismDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2006Raili Riikonen MD PhD There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations. [source] Childhood encephalopathy: viruses, immune response, and outcomeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2006Michael Clarke BSc MB ChB FRCPCH This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood-brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF: serum albumin ratio indicative of impairment of the blood,CSF and blood,brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-, levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood-brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood-brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-, was associated with a good prognosis. [source] Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI studyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2002Elizabeth R Sowell PhD The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents. [source] Cytochrome oxidase deficiency presenting as birth asphyxiaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2000Tracey A Willis MRCPI Hypoxic-ischaemic encephalopathy (HIE) was diagnosed in an infant with acidosis. At 7 weeks of age further investigations revealed abnormal neuroimaging (CT and MRI scans) and a raised plasma and CSF lactate. A skeletal-muscle biopsy at 2 months of age confirmed the diagnosis of cytochrome oxidase deficiency. The course of the patient's disorder has taken that of a static encephalopathy (cerebral palsy). Inborn disorders of the respiratory chain should be considered in the differential diagnosis of HIE. [source] Developmental changes in the modulation of respiratory rhythm generation by extracellular K+ in the isolated bullfrog brainstemDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2003Rachel E. Winmill Abstract This study tested the hypothesis that voltage-dependent, respiratory-related activity in vitro, inferred from changes in [K+]o, changes during development in the amphibian brainstem. Respiratory-related neural activity was recorded from cranial nerve roots in isolated brainstem,spinal cord preparations from 7 premetamorphic tadpoles and 10 adults. Changes in fictive gill/lung activity in tadpoles and buccal/lung activity in adults were examined during superfusion with artificial CSF (aCSF) with [K+]o ranging from 1 to 12 mM (4 mM control). In tadpoles, both fictive gill burst frequency (fgill) and lung burst frequency (flung) were significantly dependent upon [K+]o (r2 > 0.75; p < 0.001) from 1 to 10 mM K+, and there was a strong correlation between fgill and flung (r2 = 0.65; p < 0.001). When [K+]o was raised to 12 mM, there was a reversible abolition of fictive breathing. In adults, fictive buccal frequency (fbuccal), was significantly dependent on [K+]o (r2 = 0.47; p < 0.001), but [K+]o had no effect on flung (p > 0.2), and there was no significant correlation between fbuccal and flung. These data suggest that the neural networks driving gill and lung burst activity in tadpoles may be strongly voltage modulated. In adults, buccal activity, the proposed remnant of gill ventilation in adults, also appears to be voltage dependent, but is not correlated with lung burst activity. These results suggest that lung burst activity in amphibians may shift from a "voltage-dependent" state to a "voltage-independent" state during development. This is consistent with the hypothesis that the fundamental mechanisms generating respiratory rhythm in the amphibian brainstem change during development. We hypothesize that lung respiratory rhythm generation in amphibians undergoes a developmental change from a pacemaker to network-driven process. © 2003 Wiley Periodicals, Inc. J Neurobiol 55: 278,287, 2003 [source] Cytology of primary central nervous system neoplasms in cerebrospinal fluid specimensDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2002David C. Chhieng M.D. Abstract Although two-thirds of tumors occurring in the central nervous system (CNS) are primary neoplasms, only 10% of positive cerebrospinal fluid (CSF) specimens are from primary CNS tumors. In this study, we reviewed the cytologic findings of 21 positive CSF specimens from primary CNS tumors. A computer search identified 21 cases of positive CSF specimens from patients with primary CNS tumors from the archives. Follow-up included review of medical charts and histologic correlation. The specimens were from 20 patients (9 females and 11 males). Their ages ranged from 6,83 yr, old with a mean of 30 yr. The cases included 9 medulloblastomas, 7 gliomas (3 glioblastoma multiformes, 2 anaplastic astrocytomas, and 2 ependymomas), 2 germinomas, 2 non-Hodgkin's large B-cell lymphomas, and 1 ganglioneurocytoma. Two cases were classified as suspicious and the remaining as positive for malignancy. Immunocytochemistry was employed in 3 cases to support the cytologic diagnosis. These cases included one large-cell lymphoma (leukocyte-common antigen-positive), one germinoma (placental alkaline phosphatase-positive), and the ganglioneurocytoma (neuron-specific enolase- and synaptophysin-positive). There were no false-positive cases. Our results suggest that positive CSF cytology in patients with a primary CNS tumor is a reliable indicator of malignancy and reflects leptomeningeal involvement. The use of immunocytochemistry is helpful in confirming the cytologic impression in some cases. Diagn. Cytopathol. 2002;26:209,212. © 2002 Wiley-Liss, Inc. [source] Manganese speciation in human cerebrospinal fluid using CZE coupled to inductively coupled plasma MSELECTROPHORESIS, Issue 9 2007Bernhard Michalke Dr. Abstract The neurotoxic effects of manganese (Mn) at elevated concentrations are well known. This raises the question, which of the Mn species can cross neural barriers and appear in cerebrospinal fluid (CSF). CSF is the last matrix in a living human organism available for analysis before a compound reaches the brain cells and therefore it is assumed to reflect best the internal exposure of brain tissue to Mn species. A previously developed CE method was modified for separation of albumin, histidine, tyrosine, cystine, fumarate, malate, inorganic Mn, oxalacetate, ,-keto-glutarate, nicotinamide-dinucleotide (NAD), citrate, adenosine, glutathione, and glutamine. These compounds are supposed in the literature to act as potential Mn carriers. In a first attempt, these compounds were analyzed by CZE-UV to check whether they are present in CSF. The CZE-UV method was simpler than the coupled CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-MS method and it was therefore chosen to obtain a first overview information. In a second step, the coupled method (CZE-ICP-DRC-MS) was used to analyze, in detail, which of the compounds found in CSF by CZE-UV were actually bound to Mn. Finally, 13 Mn species were monitored in CSF samples, most of them being identified: Mn-histidine, Mn-fumarate, Mn-malate, inorganic Mn, Mn-oxalacetate, Mn-,-keto glutarate, Mn-carrying NAD, Mn-citrate and Mn-adenosine. By far the most abundant Mn species was Mn-citrate showing a concentration of 0.7,±,0.13,µg,Mn/L. Interestingly, several other Mn species can be related to the citric acid cycle. [source] Rapid determination of acyclovir in plasma and cerebrospinal fluid by micellar electrokinetic chromatography with direct sample injection and its clinical applicationELECTROPHORESIS, Issue 4 2006Hsin-Hua Yeh Abstract A simple MEKC with UV detection at 254,nm for analysis of acyclovir in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of acyclovir from biological matrix was performed at 25°C using a BGE consisting of Tris buffer with SDS as the electrolyte solution. Several parameters affecting the separation of the drug from biological matrix were studied, including the pH and concentrations of the Tris buffer and SDS. Using dyphylline as an internal standard, the linear ranges of the method for the determination of acyclovir in plasma and in CSF all exceeded the range of 2,50,,g/mL; the detection limit of the drug in plasma and in CSF (S/N = 3; injection 3.45,kPa, 5,s) was 1.0,,g/mL. The applicability of the proposed method for determination of acyclovir in plasma and CSF collected at 8,h after intravenous administration of 500,mg acyclovir (Zovirax®) in two patients with herpes simplex encephalitis was demonstrated. [source] Separation and determination of carnosine-related peptides using capillary electrophoresis with laser-induced fluorescence detectionELECTROPHORESIS, Issue 3 2005Ying Huang Abstract A capillary electrophoresis (CE) method with laser-induced fluorescence (LIF) detection was developed for the separation and detection of carnosine-related peptides (carnosine, anserine, and homocarnosine). A sensitive and fluorogenic regent, 3-(4-carboxybenzoyl) quinoline-2-carboxaldehyde (CBQCA) was selected as a precapillary labeling reagent for imidazole dipeptides to form isoindole derivatives. The optimized molar ratio between CBQCA and peptide was found to be 75:1, and 50 mmol/L borate buffer (pH 9.2) was used for the derivatization in order to achieve good efficiency. Three imidazole dipeptides were baseline-separated within 20 min by using 112 mmol/L sodium borate (pH 10.4,10.8) as running buffer. Concentration detection limits (signal-to-noise ratios) for carnosine, anserine, and homocarnosine were 4.73, 4.37, and 3.94 nmol/L, respectively. This method has been applied to the analysis of human cerebrospinal fluid (CSF) and meat dry powder of pig and sheep. Recoveries were in the range of 82.9,104.8% for homocarnosine in CSF. For carnosine and anserine, the recoveries are 98.3% and 80.2% in meat dry powder of pig and 111.2% and 112.8% in meat dry powder of sheep, respectively. [source] The 28-amino acid form of an APLP1-derived A,-like peptide is a surrogate marker for A,42 production in the central nervous systemEMBO MOLECULAR MEDICINE, Issue 4 2009Kanta Yanagida Abstract Surrogate markers for the Alzheimer disease (AD)-associated 42-amino acid form of amyloid-, (A,42) have been sought because they may aid in the diagnosis of AD and for clarification of disease pathogenesis. Here, we demonstrate that human cerebrospinal fluid (CSF) contains three APLP1-derived A,-like peptides (APL1,) that are generated by ,- and ,-cleavages at a concentration of ,4.5,nM. These novel peptides, APL1,25, APL1,27 and APL1,28, were not deposited in AD brains. Interestingly, most ,-secretase modulators (GSMs) and familial AD-associated presenilin1 mutants that up-regulate the relative production of A,42 cause a parallel increase in the production of APL1,28 in cultured cells. Moreover, in CSF from patients with pathological mutations in presenilin1 gene, the relative APL1,28 levels are higher than in non-AD controls, while the relative A,42 levels are unchanged or lower. Most strikingly, the relative APL1,28 levels are higher in CSF from sporadic AD patients (regardless of whether they are at mild cognitive impairment or AD stage), than those of non-AD controls. Based on these results, we propose the relative level of APL1,28 in the CSF as a candidate surrogate marker for the relative level of A,42 production in the brain. [source] Glutamine induces epileptiform discharges in superficial layers of the medial entorhinal cortex from pilocarpine-treated chronic epileptic rats in vitroEPILEPSIA, Issue 4 2009Nora Sandow Summary Purpose:, Glutamine (GLN) is a precursor for synthesis of glutamate and ,-aminobutyric acid (GABA) and has been found in the cerebrospinal fluid (CSF) at mean concentrations of 0.6 mM. Experiments on slices are usually performed in artificial CSF (aCSF) kept free of amino acids. Therefore, the role of glutamine, particularly in tissue of epileptic animals, remains elusive. Methods:, Using extracellular recordings we studied effects of GLN on field potentials and stimulus-evoked field responses in the medial entorhinal cortex (MEC) of combined entorhinal cortex hippocampal slices from pilocarpine-treated chronic epileptic rats and age-matched saline-injected control rats. Results:, In presence of GLN (0.5 and 2 mM) recurrent epileptiform discharges (REDs) were observed in slices from epileptic rats (64% and 80%, respectively), but not in slices from control rats. REDs were restricted to the superficial MEC, suppressed by the ,-Amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (30 ,M), attenuated by the inhibitor of neuronal glutamine transporters methylamino-isobutyric acid (10 mM), and apparently augmented and prolonged by the GABAA receptor antagonist bicuculline-methiodide (5 ,M). In contrast, amplitudes of stimulus evoked nonsynaptic and synaptic field responses increased in slices from control rats (+23% and +12% of the reference values) and insignificantly less or not in those of epileptic rats (+6.5% and ,0.25%, respectively). Notably, stimulus-evoked slow negative transients confined to slices of epileptic animals were reduced in amplitude (,18%). Discussion:, In combined entorhinal hippocampal slices from chronic epileptic animals, GLN induces glutamatergic REDs via neuronal uptake in superficial layers of the MEC where inhibitory function seemed to be partially preserved. [source] Lack of Neuronal Damage in Atypical Absence Status EpilepticusEPILEPSIA, Issue 12 2002Yukiyoshi Shirasaka Summary: ,Purpose: Whether status epilepticus of nonconvulsive epileptic seizures is harmful still remains controversial. To investigate this, the presence and/or extent of neuronal damage in patients with absence status epilepticus (ASE) and patients with complex partial status epilepticus (CPSE) was examined and compared. Methods: Neuron-specific enolase (NSE) in CSF was examined in the patients with ASE and compared with that of the patients having CPSE. Clinical aspects of these patients also were investigated. Results: CSF NSE levels in ASE patients were lower than those of CPSE patients and were considered as the normal values. No clinical symptoms indicated neuronal damage in the ASE patients. Conclusions: This study suggests that ASE does not induce neuronal damage. Serum NSE is not always correlated to CSF NSE, and determination of serum NSE levels may be an inappropriate method of estimating neuronal damage in some cases of ASE. [source] Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with AgingEPILEPSIA, Issue 2000Ryosuke Hanaya Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic-clonic convulsions approximately once every 30 hours from 8,16 weeks of age. A long-lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi- cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved. Methods: Hippocampal slices (40Opm) werc prepared from NER and normal Wistar rats (age; 4,29 weeks). A single rectangular pulse stimulus composed of 0.1-ms duration was delivered to the mossy fibers every 5 seconds though a bipolar electrode placed in the granular cell layer of the dentate gyrus. Intracellular recording was made from the CA3 pyramidal cell using a microelectrode containing 3M KCI intracellular recordings. A Ca2+ spike was elicited by applying a depolarizing pulse (InA, 120ms) in the cell through the recording electrode under a blockadc of Na+ and K+ channels using 1 pM tetrodotoxin and I 0mM tctraethylammonium added to the artificial CSF, respectivcly. Nicardipine (I-IOOnM), a Ca2+ channel blocker, was applicd to the bath. Results: Thirty-seven slices from I9 NER and 6 slices from 4 normal Wishe rats were used. There were no obvious changes in the resting membrane potentials of CA3 neurons between NER and Wistar rats tested. When a single stimulus was delivered to the mossy fibers, a long-lasting depolarization shift accompanied by repetitive firings followed by after-hyperpolarization werc also obtained i n hippocampal CA3 neurons of young NER (4,5 weeks of age) before occurrence of any seizurcs, although the depolarization shift in younger NER was shorter than that in NER aged more than 6 weeks. These abnormal firings werc evokcd in 58% and 30% of all CA3 neurons tested in the younger and mature NER (6,1 5 weeks of age), respectively. Furthermore, abnormal firing was not elicited in NER aged after I6 weeks. Agc-matched Wistar rats showed only single action potentials without any depolarization shift with single mossy fiber stimulation. Bath application of nicardipine (IOnM) inhibited this long-lasting depolarization shift and the accompanying repetitive firing followed by afterhypcrpolarization without affecting the first spike induced by mossy fiber stimulations. Furthermore, nicai-dipine (IOnM) inhibited the Ca2+ spikes elicited by applying a depolarizing pulse in the neurons of NER with seizures, although a higher dose (100nM) did not affect those in Wistar rats. Conclusions: These findings indicate that abnormal excitability of the NER CA3 pyramidal neurons is probably due to abnormality in the Ca2+ channcls. The abnorinal excitability was observed in NER at an age when tonic-clonic convulsions were not detected, suggesting that thc hippocampus may probably scrve as an epileptogenic focus in younger NER and the seizure impulses originating i n this area are transinittcd to the new other seizurc foci in mature NER. [source] Incidence of Traumatic Lumbar PunctureACADEMIC EMERGENCY MEDICINE, Issue 2 2003Kaushal H. Shah MD Abstract Objective: To determine the incidence of traumatic lumbar puncture (LP). Methods: A retrospective study was conducted at an urban, university tertiary care referral center with 50,000 annual emergency department (ED) visits. The study population included all patients who had cerebrospinal fluid (CSF) samples sent to the laboratory between August 15, 2000, and August 14, 2001. The numbers of red blood cells (RBCs) recorded in the first and last CSF tubes, the location where the LP was performed, and the discharge summary and the discharge diagnoses from the particular visit were obtained. All patients with intracranial pathology and CSF obtained via neurosurgical procedure or fluoroscopic guidance were excluded from the study group. Given no clear definition of traumatic LP in the literature, the incidence of traumatic LP was calculated using a cutoff of greater than 400 RBCs (visual threshold for bloody fluid) and 1,000 RBCs (arbitrary threshold selected by other authors) in CSF tube 1. Proportions were compared using chi-square statistics. Results: Seven hundred eighty-six CSF samples were recorded over one year. Twenty-four samples were obtained from patients with intracranial pathology or were obtained via a neurosurgical procedure. Of the remaining 762 CSF samples in the study population, 119 (15.6%) were traumatic using a cutoff of 400 RBCs, and 80 (10.5%) were traumatic, using a cutoff of 1,000 RBCs in tube 1. Five hundred three LPs were done in the ED and 259 were attributed to all other locations in the hospital. Using a cutoff of 400 RBCs, the incidence of traumatic LP in the ED was 13.3%, compared with 20% in the rest of the hospital (p < 0.025). Similarly, using a cutoff of 1,000 RBCs, the incidence of traumatic LP in the ED was 8.9%, compared with 13.5% in the rest of the hospital (p = 0.1). The incidence of "champagne taps" (defined as zero RBCs in the first and last tubes) in the ED was 34.4%, compared with 24.3% in the rest of the hospital (p < 0.01). Conclusions: The incidence of traumatic lumbar puncture is approximately 15% using a cutoff of 400 RBCs and 10% using a cutoff of 1,000 RBCs. In this study, the rate of traumatic lumbar puncture was significantly less (with a cutoff of 400 RBCs) and the rate of champagne tap was significantly greater for LPs done in the ED compared with the rest of the hospital. [source] Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin-specific antibodiesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Hans-Christian von Büdingen Abstract Clonally expanded plasma cells (cePC) and their presumed products, oligoclonal immunoglobulin,G bands (OCB), are characteristic findings in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). While cePC and OCB strongly suggest an involvement of B cell-dependent immune mechanisms in the pathogenesis of MS, their actual pathological relevance and target antigens remain unknown. To further understand the potential role played by cePC, we generated a panel of monoclonal antibodies (MS-mAb) from CSF-derived cePC from four patients with early or definite MS. Single-cell RT-PCR of correctly paired heavy and light chain immunoglobulin genes from individual cePC ensured the subsequent resurrection of their original antigen specificity. Immunofluorescence stainings of MS lesion tissue with MS-mAb revealed myelin reactivity in the cePC repertoire of all four patients and intracellular filament reactivity in one patient. While myelin staining by MS-mAb was only rarely detectable in non-MS CNS white matter tissue, it was greatly enhanced at the edge of demyelinating lesions in MS brain tissue. Our findings provide conclusive evidence for the presence of an antigen-driven B cell response in the CSF of MS patients directed against epitopes present in areas of myelin degradation. [source] Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2010L. Fialová Background:, The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods:, We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results:, Serum levels of anti-NFL were higher in ALS patients than in controls (P < 0.005). Serum anti-NFL antibodies and intrathecal anti-NFM antibodies were related to patient disability (serum anti-NFL: P < 0.05; intrathecal anti-NFM: P < 0.05). Anti-NFL levels were significantly correlated with anti-NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti-NFL and anti-NFM antibodies significantly correlated between serum and CSF in the ALS group (anti-NFL: P < 0.0001; anti-NFM: P < 0.001) and in the control group (anti-NFL: P < 0.05; anti-NFM: P < 0.05). Conclusions:, Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS. [source] Cerebrospinal fluid biomarkers of white matter lesions , cross-sectional results from the LADIS studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010M. Jonsson Background and purpose:, White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. Methods:, Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid ,, ,- and ,-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau181), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. Results:, Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau181 and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. Conclusions:, The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers. [source] Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitorsEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010K. Schultz Background:, Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. Methods:, CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression. Results:, No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not. Conclusions:, Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias. [source] HHV-6 infection in multiple sclerosis.EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010A clinical, laboratory analysis Background and purpose:, To elucidate the role of human herpesvirus-6 (HHV-6) in the development of multiple sclerosis (MS). Patients and methods:, Nine patients with MS and with acute or chronic HHV-6 infection were evaluated. Results:, Intrathecal antibody production to HHV-6 and oligoclonal IgG bands in the cerebrospinal fluid (CSF) was observed in two patients with a clinically definite MS and chronic HHV-6 infection (based on the presence of HHV-6 specific antibodies in the CSF). A temporal association between the symptoms of clinically possible MS and acute primary HHV-6A infection (based on avidity of HHV-6 specific antibodies) was observed in two patients. Conclusions:, Human herpesvirus-6 infection may be an associated agent in some MS cases. Viral studies are needed to identify a possible viral etiology and give specific therapy. [source] Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co-twin studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2010A. Hietaharju Background and purpose:, The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS. Methods:, Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)-6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay. Results:, A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co-twins. Conclusion:, As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS. [source] MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus-specific IgG antibodies produced in vivo and by CSF B cells in vitroEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2009G. Skorstad Background:, Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type-1 (HSV-1) is a characteristic feature multiple sclerosis (MS). Methods:, We have used isoelectric focusing-immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV-1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease. Results:,In vitro synthesis of IgG by PBL was not detected in any patient. In contrast, in vitro synthesis by CSF cells of oligoclonal IgG and oligoclonal IgG antibodies to one or two of the three viruses tested was observed in all six patients. The clonal patterns of the in vitro synthesized IgG and virus specific IgG differed to varying extent from those synthesized intrathecally in vivo. However, in each patient, the in vitro and in vivo intrathecally produced antibodies displayed specificity for the same viruses. The addition of B cell activating factor (BAFF) had no effect on the amounts or clonal patterns of either total IgG or virus-specific IgG produced by CSF cells in vitro. Conclusion:, Virus specific B cells capable of spontaneous IgG synthesis are clonally expanded in the CSF of patients with MS. The B-cell repertoire in CSF samples is only partially representative of the intrathecal B-cell repertoire. [source] Increased levels of inflammatory chemokines in amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2009J. Kuhle Background and purpose:, Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS. Methods:, We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1, (MIP-1,), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients. Results:, MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = ,0.407; P = 0.075). Conclusions:, We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease. [source] The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkersEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009M. Khademi Background:, Natalizumab affects systemic cytokine expressions and clinical course in relapsing,remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP)-9 and osteopontin (OPN) in CSF, and clinical outcome measures in 22 natalizumab-treated RRMS patients. Methods:, mRNA levels of cytokines in cells were detected with real-time RT-PCR. Protein levels of OPN and MMP-9 were measured by ELISA. Results:, Natalizumab reduced CSF cell counts (P < 0.0001). Tumor necrosis factor (TNF) and interferon-, (IFN-,) mRNAs were significantly increased in PBMCs. In contrast, expressions of IFN-, and interleukin (IL)-23 were decreased but IL-10 increased in the CSF cells. OPN and MMP-9 were reduced in the CSF. Patients being in remission at baseline showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy. Conclusions:, Natalizumab attenuates pro-inflammatory mediators intrathecally and the reduced pro-inflammatory milieu may allow increased production of the anti-inflammatory mediator IL-10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune-modifying treatment which could be used as biomarkers for this therapy. [source] CSF biomarker profile and diagnostic value in vascular dementiaEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2009G. P. Paraskevas Background and purpose:, The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (,T) or hyperphosphorylated at threonin-181(,P-181) form and beta amyloid peptide 1,42 (A,42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD. Methods:, The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls. Results:, Alzheimer's disease and MD showed increased levels of ,T, ,P and reduced levels of A,42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying ,85% of patients, either in the form of a discriminant function or in the form of the ,T × ,P-181/A,42 formula. Conclusions:, Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice. [source] Assessment of idiopathic normal pressure patients in neurological practice: the role of lumbar infusion testing for referral of patients to neurosurgeryEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2008A. Brean Background and purpose:, In neurological practice patients with tentative idiopathic normal pressure hydrocephalus (iNPH) usually are referred to neurosurgery based on clinical and radiological findings. Hydrodynamic assessment using lumbar infusion testing might be helpful in selecting patients. To retrospectively analyse lumbar infusion tests done in neurological practice in iNPH patients to see how infusion test results relate to the clinical course and shunt response. Materials and methods:, Sixty-three consecutive patients with Possible/Probable iNPH were tested during a 1-year period. The pre-operative lumbar infusion tests were assessed according to two strategies: (i) Determining the resistance to cerebrospinal fluid (CSF) outflow (Rout). (ii) Quantification of the CSF pressure (CSFP) pulsatility during lumbar infusion (Qpulse). The results were related to the prospectively followed clinical course and shunt response after 12 months. Results:, The lumbar infusion-derived parameters Rout and Qpulse related weakly. Shunt response after 12 months was not related to Rout, but was highly related to the Qpulse. False negative results of lumbar infusion testing were observed in 16% of the patients. Discussion:, In neurological practice lumbar infusion testing may be useful for determining which patients to refer to neurosurgery. Our data favour determination of CSFP pulsatility (Qpulse) rather than Rout for prediction of shunt response. [source] Brain barrier dysfunction in Cuban Epidemic Optic NeuropathyEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2008A. González-Quevedo Monteagudo Background and purpose:, There are practically no references to cerebrospinal fluid(CSF) studies in tropical or nutritional neuropathies. In the present paper we present the results of CSF studies in patients with Cuban Epidemic Optic Neuropathy (CEON) during epidemic and endemic periods, with an appraisal as to the contribution of brain barriers, function in the pathophysiology of this disease. Methods:, Two hundred and five patients with CEON were studied during the epidemic period (1992,1993) and 12 patients outside the outbreak (1995,1997). CSF protein determination and electrophoresis were carried out, as well as serum and CSF albumin and immunoglobulin G (IgG) quantitation for calculating IgG and Qalb indexes, in order to evaluate intrathecal IgG synthesis and the permeability of the blood,CSF barrier (B-CSF B). Results:, One fourth of the patients had increased permeability of the B-CSF B, but damage was more frequent between 16 and 60 days from onset of disease, disappearing after 120 days. B-CSF B dysfunction was more prevalent in patients with severe neurological impairment, although it was not related to the severity of ophthalmological damage. The group of patients studied outside of the outbreak (endemic period) showed similar results. Discussion:, The possible association of increased permeability of the B-CSF B with oxidative stress, which lies on the basis of this epidemic outbreak, is discussed. [source] Cerebrospinal fluid 14-3-3-, protein level in eight HIV-negative cryptococcal meningitis adultsEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2008W. N. Chang The clinical data and cerebrospinal fluid (CSF) 14-3-3-, protein detection of eight adult HIV-negative cryptococcal meningitis (CM) cases were examined. The eight cases included six males and two females aged 35,70 years (mean = 49.8 years). The duration between the onset of CM symptoms and the first CSF study ranged from 1 to 60 days. Initial neuroimaging study was abnormal in 87.5% (7/8) of the cases. All the eight had positive initial and subsequent follow-up CSF 14-3-3-, protein detection. The densitometric values of CSF 14-3-3-, protein were not correlated with either the CSF white blood cell counts or the therapeutic results. The therapeutic results showed that three cases died and five survived. Significant neurologic deficits were shown in 60% (3/5) of the survivors. This study revealed that HIV-negative CM patients have elevated CSF 14-3-3-, protein levels, and that this level is not changed with a short-term treatment. [source] Early diagnosis of rhinocerebral mucormycosis by cerebrospinal fluid analysis and determination of 16s rRNA gene sequenceEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2007D. Bengel A 40-year-old diabetic woman was diagnosed with rhinocerebral mucormycosis. Cerebral mucormycosis is an acute life-threatening disease, which is caused by fungi of the class Phycomycetae. Clinical suspicion and detection of the fungal hyphae in cerebrospinal fluid (CSF) led to early diagnosis, subsequently confirmed by immunohistochemistry and molecular analysis of fungal RNA. Early infiltration of the infectious agent into the central nervous system resulted in septic thrombosis of the cavernous sinus, mycotic meningoencephalitis, brain infarctions as well as intracerebral and subarachnoidal hemorrhages. Despite immediate high-dose antimycotic treatment, surgical debridement of necrotic tissue, and control of diabetes as a predisposing factor, the woman died 2 weeks after admission. Although fungal organisms are rarely detectable in CSF specimens from patients with mycotic infections of the central nervous system, comprehensive CSF examination is beneficial in the diagnosis of rhinocerebral mucormycosis. Furthermore, a concerted team approach, systemic antifungal agents and early surgical intervention seem to be crucial for preventing rapid disease progression. [source] | ||||||||||||||||||||||||||||||||||