Decreased cerebrospinal fluid levels of beta-endorphin in Japanese patients with Joseph disease

We measured the cerebrospinal fluid (CSF) levels of beta-endorphin in 7 Japanese patients with Joseph disease and compared them with control values. The 7 patients included 4 with type I and 3 with type II disease; their mean age was 45.7 +/- 12.09 years. Diseased controls were matched in age to the patients studied. In these patients, CSF beta-endorphin level was significantly lower than in the controls (40% of normal values). An alteration in CSF beta-endorphin level may explain some of the neurological impairment found in Joseph disease.     

Prolactin levels in cerebrospinal fluid of patients with chronic schizophrenia

Baseline concentrations of prolactin (PRL) was determined in the CSF of 28 lobotomized and 28 non-lobotomized patients with chronic schizophrenia. The mean PRL level of the female patients was significantly higher than that of the male patients (p < 0.001). In addition, non-lobotomized patients had significantly higher concentrations of CSF PRL than patients of the lobotomized group (p < 0.05). On the other hand, patients belonging to the latter group exhibited significantly more central as well as cortical brain atrophy than the patients on whom no psychosurgery had been performed (0.05 > p < 0.001). The significance of cerebrospinal PRL as an index of central dopamine metabolism is discussed.     

Decreased lumbar cerebrospinal fluid levels of monoamine metabolites in vascular dementia

The levels of the monoamine metabolites 5-hydroxy-indoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 56 patients with vascular dementia (VAD) and 57 healthy controls. Despite CSF sampling under standardized conditions, the variability in values was wide among both patients and controls. This suggests that yet unknown factors affect the lumbar CSF concentrations of monoamine metabolites. The VAD group showed significantly lower mean concentrations of 5-HIAA (p < .001) and HVA (p < .001) than the control group. These low concentrations appear to be no disease-specific phenomenon, but may be attributable to subcortical white-matter changes or a decreased production of monoamines, which are dependent on oxygen for their synthesis.     

Decreased interleukin-6 level in the cerebrospinal fluid of patients with Alzheimer-type dementia

We examined IL-6 levels in the cerebrospinal fluid (CSF) of patients clinically diagnosed with Alzheimer-type dementia (ATD) and with vascular dementia (VD) and of age-matched normal subjects. The IL-6 levels in the CSF of ATD, but not VD patients, were significantly decreased. In the early onset ATD patients (disease onset < 65 years), IL-6 levels were reduced to 21% of the control level. The IL-6 levels in the CSF were not associated with the severity of the dementia or the duration of the disease since the identification of the first symptoms.     

Excitatory amino acid levels in cerebrospinal fluid of patients with infantile spasms

Infantile spasm is an age-specific epileptic encephalopathy. Long-term intellectual outcome of affected infants remains poor. The pathogenesis of infantile spasms, as well as the development of mental retardation, remains unclear. Increased excitatory amino acid neurotransmission may play a role in neuronal dysfunction and epilepsy. To study the significance of cerebrospinal fluid excitatory amino acids in infantile spasms, we determined glutamate and aspartate concentrations in cerebrospinal fluid of 13 patients with infantile spasms and 13 controls. The aspartate level in cerebrospinal fluid of the patients with infantile spasms (968 +/- 416 nmol/l) was higher than the control group (426 +/- 272 nmol/l). No difference in the mean glutamate levels was found between the patients (966 +/- 395 nmol/l) and the controls (1135 +/- 594 nmol/l). The elevated aspartate levels in cerebrospinal fluid of the patients with infantile spasms might be secondary to change in metabolism of aspartate. Aspartate is an excitatory and neurotoxic neurotransmitter, which might have a role in triggering the spasms and the development of neuronal dysfunctions in the patients with infantile spasms.     

Neurotrophic factors in cerebrospinal fluid and serum of patients with Rett syndrome

Rett syndrome is now considered to be a neurodevelopmental disease. Its cause is unknown, but it has been suggested that neuronal growth factors and neurotransmitters play important roles. We measured levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in cerebrospinal fluid, and nerve growth factor and brain-derived neurotrophic factor in serum in child and adolescent patients with Rett syndrome. Levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in cerebrospinal fluid were below the limit of sensitivity of the methods used. Serum levels of nerve growth factor and brain-derived neurotrophic factor did not differ from control values. In Rett syndrome, the normal serum levels of nerve growth factor together and previously reported low levels of the factor in cerebrospinal fluid indicate that the latter may reflect low levels of nerve growth factor in the central nervous system.     

Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus

OBJECTIVE: Forty percent of standard cerebrospinal fluid shunts implanted for the treatment of pediatric hydrocephalus fail within the first year. Two new shunt valves designed to limit excess flow, particularly in upright positions, were studied to compare treatment failure rates with those for standard differential-pressure valves. METHODS: Three hundred-forty-four hydrocephalic children (age, birth to 18 yr) undergoing their first cerebrospinal fluid shunt insertion were randomized at 12 North American or European pediatric neurosurgical centers. Patients received one of three valves, i.e., a standard differential-pressure valve; a Delta valve (Medtronic PS Medical, Goleta, CA), which contains a siphon-control component designed to reduce siphoning in upright positions; or an Orbis-Sigma valve (Cordis, Miami, FL), with a variable-resistance, flow-limiting component. Patients were monitored for a minimum of 1 year. Endpoints were defined as shunt failure resulting from shunt obstruction, overdrainage, loculations of the cerebral ventricles, or infection. Outcome events were assessed by blinded independent case review. RESULTS: One hundred-fifty patients reached an endpoint; shunt obstruction occurred in 108 (31.4%), overdrainage in 12 (3.5%), loculated ventricles in 2 (0.6%), and infection in 28 (8.1%). Sixty-one percent were shunt failure-free at 1 year and 47% at 2 years, with a median shunt failure-free duration of 656 days. There was no difference in shunt failure-free duration among the three valves (P = 0.24). CONCLUSION: Cerebrospinal fluid shunt failure, predominantly from shunt obstruction and infection, remains a persistent problem in pediatric hydrocephalus. Two new valve designs did not significantly affect shunt failure rates.     

Neurosyphilis and penicillin levels in cerebrospinal fluid

Because neurosyphilis may progress despite therapy with the recommended penicillin regimens, 15 subjects with positive tests for syphilis in the serum and cerebrospinal fluid (CSF) were studied. All of these patients had CSF pleocytosis. Two received penicillin G (5 and 10 million units per day intravenously, respectively) and 13 received benzathine penicillin G, 3.6 million units per week intramuscularly; treatment lasted four weeks. During intravenous and after intramuscular penicillin therapy, a spinal tap was performed on all subjects; later, assays were done. Of two patients who received intravenous penicillin G, one had 0.3 mug/ml and the other had 2.4 mug/ml penicillin in the CSF. Twelve of 13 patients who received benzathine penicillin G had no detectable penicillin in the CSF; one patient had 0.1 mug/ml penicillin in the CSF.     

Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer's patients

Apolipoprotein D (apoD) is a member of the lipocalin family of proteins. Most members of this family are transporters of small hydrophobic ligands, although in the case of apoD, neither its physiological function(s) nor its putative ligand(s) have been unequivocally identified. In humans, apoD is expressed in several tissues, including the CNS, and its synthesis is greatly increased during regeneration of rat peripheral nerves. As apoD may have an important function in the nervous system and, particularly, in nerve regeneration, we measured immunoreactive apoD levels in the hippocampus and in CSF of patients with either Alzheimer's disease (AD) or other neuropathologies. In parallel, we determined the concentrations of apolipoprotein E (apoE), another apolipoprotein also implicated in nerve regeneration and in the etiology of AD. Levels of apoD but not apoE were increased in the hippocampus of AD patients compared with controls. ApoD concentrations, as determined by radioimmunoassay, were significantly increased in the CSF of AD patients (4.23 +/- 1.58 microg/ml) and patients with other pathologies (3.29 +/- 1.35 microg/ml) compared with those in the CSF of normal subjects (1.15 +/- 0.71 microg/ml). Although the differences were smaller than for apoD, the mean apoE concentrations in the CSF of both groups of patients were also significantly higher than those of controls. In AD patients, apoD, but not apoE, levels in CSF and hippocampus increased as a function of inheritance of the epsilon4 apoE allele. This study therefore demonstrates that increased apoD levels in the hippocampus and in CSF are a marker of neuropathology, including that associated with AD, and are independent of apoE concentrations.     

Decreased levels of amniotic fluid oxytocinase activity in preeclampsia

Oxytocinase (EC 3.4.11.3) activity was determined in 80 amniotic fluid samples obtained from 40 normotensive primigravidas (median age 27 years) and 40 primigravidas (median age 29 years) with pregnancies complicated by preeclampsia between 32 and 39 weeks of gestation. The enzyme activity was significantly lower in preeclampsia than in normal pregnancy with matched gestations (p < 0.01). Considering the possible involvement of vasopressin and angiotensin II in preeclampsia, it is suggested that the enzyme which degrades these pressor hormones may play a role in the pathogenesis of hypertensive pregnancy.     

Simultaneous recording of cerebrospinal fluid pressure and middle cerebral artery blood flow velocity in patients with suspected symptomatic normal pressure hydrocephalus

Whether anaphylactic histamine release from rat peritoneal mast cells is influenced by betahistine, a histamine H1-receptor agonist/H3-antagonist, and dimaprit, an H2-agonist, was examined. Treatment with dimaprit at 6 and 60 microM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 microM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 microM for 1 to 20 min and for 5 to 20 min, respectively, caused a time-dependent inhibition of the release, but up to 30 min treatment with 8 and 80 microM betahistine had no effect. The decreased histamine release induced by dimaprit was recovered by neither mepyramine nor cimetidine. However, thioperamide, an H3-selective antagonist, dose-dependently restored the diminished release. From these results, the inhibition of anaphylactic histamine release by dimaprit is not produced by the stimulation of H2-receptors, but involves the stimulation of H3-like receptors or H3-subtype receptors, which are distinct from the H3-receptors located in brain, and suggests that the receptor plays an important role in the negative feedback regulation of histamine release.     

Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques.

There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. Several studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of infants. The main goal of this study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on Cayo Santiago, PR. CSF oxytocin levels were examined in relation to individuals' demographic and reproductive characteristics as well as plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7–26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38–134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. These findings: 1) provide feasibility data for examining CSF oxytocin levels in free-ranging non-human primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Research is now required to examine CSF oxytocin levels in the context of social functioning in free-ranging rhesus monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diagnostic studies of cerebrospinal fluid in patients with multiple sclerosis

The diagnostic criteria postulated by Poser necessitate clinical and laboratory CSF analysis for establishment of the diagnosis of definitive multiple sclerosis. The present paper reports methods for CSF examinations relating to multiple sclerosis with regard to the examinations suggested by the Charcot Foundation. In the course of CSF analysis, it is important to discriminate between the immunoglobulins present in normal amounts, those synthesized locally in pathological quantities and those penetrating across the damaged blood-CSF barrier. Normally, a parallel assay of CSF and serum specimens is carried out in the course of quantitative and qualitative protein analysis. In 37 patients with clinical multiple sclerosis, we determined the albumin and the immunoglobulin classes IgG, IgA and IgM, using laser nephelometry. An elevated IgG index was found in 76% of the cases, which points to local IgG snythesis and might be proof of the humoral immune response. The albumin quotient, which is suitable for examination of the integrity of the blood-CSF barrier, was within the reference range. Qualitative protein analysis was performed by means of electrophoresis on agarose-gel and isoelectric focusing. Agarose-gel electrophoresis revealed oligoclonal gammopathy in 68%, in contrast with the 91% demonstrated by isoelectric focusing. Comparison of the two kids of qualitative protein analyses indicated that isoelectric focusing was more sensitive for the detection of oligoclonal bands, in support of the literature finding.     

Proinflammatory cytokine levels in cerebrospinal fluid from children with acute encephalitis]

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i.v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22% and 21% for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.     

Nitrite and nitrate levels in cerebrospinal fluid of normal subjects

In order to evaluate the involvement of nitric oxide in neurologic disorders it is important to generate controlled values of its metabolites nitrite and nitrate in human cerebrospinal fluid (CSF). Samples of CSF obtained from 14 patients without neurologic diseases were analysed for nitrite and nitrate concentration by reverse phase chromatography with ultraviolet (UV) detection. For comparison, the levels of nitrite in the same samples were also measured by reverse phase chromatography coupled with electrochemical detection and those of nitrate by ion chromatography coupled with UV detection. A good correlation was found for the concentration values of both ions obtained with the two procedures. Then, 10.41 +/- 0.47 ng/ml of nitrite and 2.92 +/- 0.37 ng/ml of nitrate could be regarded as reliable values in control subjects. No correlation between age and levels of nitrite and nitrate was observed.     

Antibodies against Helicobacter pylori were detected in the cerebrospinal fluid obtained from patients with Guillain-Barré syndrome

We examined the antibodies against Helicobacter pylori proteins in the cerebrospinal fluid (CSF) of 7 patients with Guillain-Barré syndrome (GBS). Crude H. pylori antigens, fractionated heat shock protein (HSP), and urease B (UB) from H. pylori antigens were separated by SDS-PAGE. With Western blot analysis, four of seven CSF samples had several IgG antibodies against H. pylori proteins, including HSP and UB. No cross reactivity against Campylobacter jejuni was observed. These antibodies may be involved in the immune responses of patients with GBS.     

Marker proteins in cerebrospinal fluid of patients with grave craniocerebral injury

The permeability of the blood-brain barrier for the cerebrospinal fluid marker proteins has been assessed in patients with grave craniocerebral injuries. The content of albumin and alpha 2-macroglobulin in the survivors decreased with time and by day 7 after the injury was virtually normal. In patients who died the content of these proteins was reliably increased starting from day 1. By day 7 the content of albumin in the cerebrospinal fluid approached the norm in this group, whereas the content of alpha 2-macroglobulin remained increased. The level of IgG surpassed the normal value on day 1 only in the patients who died, and later it did not differ from the norm in both groups.     

Structural-functional interrelations in patients with an epileptic syndrome in posttraumatic hydrocephalus

Overall forty two patients presenting with epileptic syndrome in posttraumatic hydrocephalus in the remote period of light closed craniocerebral injury, who ranged from 16 to 60 years old, were examined. Degree of severity and variety of posttraumatic hydrocephalus were assessed by findings from axial computerized tomography, pneumoecephalography, magnetoresonance tomography. All patients underwent electroencephalography. The examinees were predominantly those persons presenting with light and internal symmetrical hydrocephalus. 57.2% of patients developed cerebral seizures within the first 5 years of sustaining the injury. Normal EEG was recordable in those patients with epileptic syndrome presenting with light and internal symmetrical hydrocephalus. Apparent diffusive disturbances in the bioelectrical activity of the brain were more common in moderately severe hydrocephalus and in mixed hydrocephalus. The presence of paroxysmal activity is a particular characteristic of patients with epileptic syndrome in outer hydrocephalus. A distinguishing feature of internal asymmetrical hydrocephalus is an observation of a decrease in the general level of biopotentials.