Plasma and cerebrospinal fluid gamma-aminobutyric acid in neurological disorders.

In 49 patients with various neurological disorders plasma and CSF gamma-aminobutyric acid (GABA) concentrations were determined by radioreceptor assay. The CSF GABA concentration of 127 +/- 47 pmol/ml (range: 65-275; n = 52) was independent of the age, the sex and the intake of various drugs including benzodiazepines, baclofen and antidepressants. Patients with diverse neurological disorders such as multiple sclerosis, ischaemic strokes, intracranial tumour and polyneuropathies had similar CSF GABA levels. The mean plasma GABA concentration was 309 +/- 79 pmol/ml (range: 179-498; n = 44). The correlation between the GABA concentrations of CSF and plasma was very poor (r = 0.18; n = 44). Therefore plasma GABA is not a suitable indicator for CSF GABA.     

The cerebrospinal fluid level of glial fibrillary acidic protein is increased in cerebrospinal fluid from Alzheimer's disease patients and correlates with severity of dementia.

To gain insight of the underlying mechanisms of astroglial response to Alzheimer's disease (AD), the level of glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) from controls and AD subjects were immunochemically determined, and the correlation between that level and dementia severity of AD patients was evaluated. Means and SD of CSF levels of GFAP for the young control group (from 1 to 25 years, mean +/- SD 14.2 +/- 5.0, n = 13) adult control (from 26 to 55 years, 41.6 +/- 10.1, n = 9) and senescent control (older than 56 years, 65.4 +/- 8.0, n = 8) were 2.96 +/- 1.04, 2.80 +/- 1.46 and 3.99 +/- 1.55 ng/ml, respectively, and the CSF level of GFAP was not dependent on age (ANOVA, p = 0.17). While that of the AD patient group (n = 27, 70.8 +/- 8.0 years) was 8.96 +/- 7.80 ng/ml, significantly higher than that of both the all-control (3.19 +/- 1.39 ng/ml, t test, p < 0.001) and age-matched senescent (3.99 +/- 1.55 ng/ml, t test, p < 0.005) control groups. The receiver-operator characteristic (ROC) curve revealed that the GFAP concentration at 5 ng/ml in CSF could serve as a cutoff value. The CSF level of GFAP in the moderately to severely demented patients (MMSE /= 18, 6.85 +/- 5.76 ng/ml, n = 18; ANOVA, p < 0.05). These findings together with our previous report on an increase in the CSF level of apolipoprotein E suggest that degeneration and stimulation of astrocytes takes place concurrently in the AD brain.     

Relationships between glutamate and monoamine metabolites in cerebrospinal fluid and serum in healthy volunteers

The concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG), and glutamate were determined in cerebrospinal fluid (CSF) and serum in 10 healthy volunteers. The monoamine metabolites were measured by mass fragmentography and the glutamate by high-performance liquid chromatography. The level of glutamate in CSF was low (0.34 +/- 0.14 nmol/ml) in comparison with previously published values. The concentrations of monoamine metabolites in CSF were in close agreement with earlier findings. There were negative correlations between the concentrations of HVA (r = -0.82, p less than 0.01) and 5-HIAA (r = -0.77, p less than 0.01) and glutamate in CSF, but not in serum. The serum levels of HMPG and glutamate were negatively correlated (r = -0.95, p less than 0.001), but not the CSF levels. The HMPG levels in serum and CSF were positively correlated (r = 0.94, p less than 0.001), but not the HVA and the 5-HIAA levels. The serum and CSF levels of glutamate were positively correlated (r = 0.67, p less than 0.05). The results indicate relationships among the metabolism of dopamine, serotonin, and glutamate in the brain and between the metabolism of noradrenaline and glutamate in peripheral tissue.     

Low CSF GABA concentration in children with febrile convulsions,untreated epilepsy,and meningitis

In 14 children with epilepsy, 51 with febrile convulsions and 22 with meningitis gamma-aminobutyric acid (GABA) concentrations in lumbar CSF were determined. While the mean for CSF GABA concentrations for all epileptic children was unchanged [144 (range: 73-285) pmol/ml; controls: 148 (range: 90-243) pmol/ml] extraordinarily high GABA levels were found in the CSF of two children on valproate (525 and 557 pmol/ml) and remarkably low GABA concentrations in hitherto untreated epileptic children [109 (range: 67-176) pmol/ml]. Children with febrile convulsions [103 (range: 63-170) pmol/ml] and acute meningitis [105 (range: 65-171) pmol/ml] had significantly decreased CSF GABA concentrations (P less than 0.001 and P less than 0.02 compared with controls). The data indicate that valproate intake increases dramatically the GABA concentrations in the CSF of epileptic children. Furthermore, the study supports the concept that low GABAergic activity within the CNS may be one cause for an increased seizure frequency.     

Glutamic acid decarboxylase in cerebrospinal fluid in infancy and childhood. Part I. Glutamic acid decarboxylase activity in cerebrospinal fluid of normal infants and children

Glutamic acid decarboxylase (GAD) activity in the cerebrospinal fluid (CSF) of normal infants (n:14) and children (n:28) was determined by measuring the amount of 14CO2 released from L-[1-14C]-glutamic acid. The mean GAD activity in CSF of infants and children was 5.2 +/- 2.5 pmol CO2 formed/hr/ml. Dividing these subjects into 4 groups according to age, GAD activities in CSF were 5.4 +/- 1.6 pmol CO2 formed/hr/ml in neonates (0-1 m), 3.6 +/- 1.6 pmol CO2 formed/hr/ml in infants (2-12 m), 3.9 +/- 1.1 pmol CO2 formed/hr/ml in young children (2-6 yr) and 7.1 +/- 2.3 pmol CO2 formed/hr/ml in school children (7-16 yr), respectively. In neonates and school children, GAD activities were significantly higher (p less than 0.001) than those in the other age groups. In infants under 6 months of age, a significantly negative correlation between GAD activity in CSF and their ages was recognized (r = -0.52, p less than 0.001). In infants and children ranging from 6 months to 16 years of age, a significantly positive correlation between GAD activity in CSF and their ages was found (r = 0.67, p less than 0.001). These data suggest that high GAD activity in neonates may be due to hypoxia at birth and the activity gradually increases from 6 months to 15 years of age.     

beta-Endorphin-like immunoreactivity in cerebrospinal fluid of patients with Alzheimer's disease and Parkinson's disease

beta-Endorphin-like immunoreactivity (beta-EP-LI) in cerebrospinal fluid (CSF) was measured in 42 patients with Alzheimer's disease (AD), 36 patients with Parkinson's disease (PD), and 35 controls. Values for patients with Alzheimer's disease (10.9 +/- 2.8 pmol/l) seemed to be lower than those for controls (12.9 +/- 2.5 pmol/l) (P less than 0.05). In addition, the severely demented patients had lower values than the moderately demented (P less than 0.01). In patients with Parkinson's disease no significant difference in beta-EP-LI values was observed compared to the controls. The data suggest, that processing of pro-opiomelanocortin, precursor of beta-endorphin, and the mechanism of cognitive impairment may differ in Alzheimer's disease and Parkinson's disease.     

Immunoreactive leukotriene C4 levels in CSF of MS patients

Using a sensitive and specific radioimmunoassay levels of leukotriene (LT)C4-like material were estimated in lumbar cerebrospinal fluid (CSF) samples from patients with multiple sclerosis (MS) in comparison to control patients with or without inflammatory processes in the central nervous system (CNS). Levels of LTC4-like material were significantly elevated (p less than 0.01) in CSF from patients with inflammatory diseases such as meningitis, polyradiculitis or meningoencephalitis (57 +/- 53 pg/ml, n = 16) as compared to those from control patients without inflammatory or immunological CNS diseases (21 +/- 16 pg/ml, n = 42). By contrast, LTC4-like material was 16 +/- 7 pg/ml in first manifestations of MS (n = 7). 21 +/- 16 pg/ml in remitting-relapsing MS (n = 15) and 10 +/- 6 pg/ml in chronic progressive MS (n = 8). These results argue against a significant pathophysiological role of cysteinyl-LT in MS.     

CSF and plasma vasopressin concentrations in dementia.

In 16 patients with primary degenerative dementia mean CSF vasopressin concentration was lower (0.9 +/- 0.1 pg/ml (mean +/- SEM)) than in 28 control patients (1.3 +/- 0.1 (mean +/- SEM)) (p less than 0.01). In 18 patients with normal pressure hydrocephalus and potentially reversible dementia mean CSF vasopressin concentration (1.2 pg/ml +/- 0.1 (mean +/- SEM)) was not different from that found in controls. Several of the demented patients had inappropriate plasma vasopressin concentrations suggesting a defect in osmoregulation. These findings encourage further clinical trials of vasopressin in patients with primary degenerative dementia, but it is emphasised that the low CSF vasopressin concentration in these patients might be only a nonspecific phenomenon due to the diffuse loss of cells within the central nervous system.     

Total biopterin levels in the ventricular CSF of patients with Parkinson's disease: a comparison between akineto-rigid and tremor types

Total L-erythro-biopterin (T-BP) levels in the ventricular cerebrospinal fluid (CSF) were measured in 43 patients with Parkinson's disease (PD) and 12 age-matched neurological controls. In 5 of the PD patients and 1 control, lumbar CSF T-BP values were also measured. The mean ventricular CSF T-BP level in the PD patients, 15.6 +/- 0.5 pmol/ml (mean +/- SE), was significantly lower than that in the controls (21.3 +/- 1.4 pmol/ml, P less than 0.0001). The mean T-BP concentration in the ventricular CSF was 1.9 times higher than that in the lumbar CSF (P less than 0.0005), indicating a rostrocaudal gradient for the T-BP value in the CSF. When the PD patients were classified according to their predominant clinical features into 24 akineto-rigid (A-R) type and 19 tremor (T) type, there was a significant negative correlation between the T-BP levels and duration of illness only for the A-R type patients (rho = -0.605, P less than 0.005). No such significant correlation was found in the T type patients. These results may indicate a difference of pathophysiological changes in the brain between the 2 types of PD.     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease

We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer's disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean +/- SD rCMRgluc were 0.20 +/- 0.03 micromol/ml/min for the demented twins, 0.21 +/- 0.03 micromol/ml/min for their non-demented co-twins, and 0.23 +/- 0.02 micromol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean +/- SD rCMRgluc were 0.27 +/- 0.05, 0.28 +/- 0.04, and 0.32 +/- 0.02 micromol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.     

Studies on neurotransmitter markers and neuronal cell density in the cerebellar system in olivopontocerebellar atrophy and cortical cerebellar atrophy

Glutamate, aspartate and gamma-aminobutyrate (GABA) concentrations and choline acetyltransferase (ChAT) activity were measured in postmortem cerebellar cortical areas and brainstem nuclei of 10 normal controls, 5 patients of olivopontocerebellar atrophy (OPCA) with multiple system atrophy (MSA) and 2 patients of cortical cerebellar atrophy (CCA). In addition, the neuronal cell density in the cerebellar cortex and the brainstem nuclei was determined, and the correlation between neurotransmitter markers and the neuronal cell densities were investigated. Glutamate and aspartate concentrations in the cerebellar cortical tissues were markedly varied from case to case of MSA (OPCA) and CCA patients. However, glutamate concentration in the anterior vermis showed a positive correlation coefficient with the density of granule cells (r = 0.554, 0.05 less than P less than 0.10) and, those in the posterior vermis and in the cerebellar hemisphere were positively correlated with cells in the inferior olive (r = 0.707 and 0.607, P less than 0.05, respectively). Aspartate concentration in the anterior vermis also has a positive correlation coefficient (r = 0.571, 0.05 less than P less than 0.10) with the density of cells in the inferior olive. GABA concentrations in the dentate nucleus were decreased in all cases of MSA (OPCA) and CCA, and were positively correlated with the degree of loss of Purkinje cells (r = 0.765, P less than 0.01). ChAT activities were decreased in certain cases of MSA (OPCA), but conversely, increased in CCA patients. ChAT activity in the posterior vermis has a positive correlation coefficient (r = 0.613, 0.05 less than P0.10) with the cell density in the pontine nucleus. A possibility of a compensatory increase of ChAT activity in CCA patients was discussed.     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Involvement of NMDA and AMPA/kainate receptors in the effects of endogenous glutamate on extracellular concentrations of dopamine and GABA in the nucleus accumbens of the awake rat

We have investigated the effects of perfusion of the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) on the endogenous glutamate-evoked changes of extracellular dopamine and alpha-aminobutyric acid (GABA) in the nucleus accumbens of the awake rat. Local infusion of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxilic acid in the nucleus accumbens produced an increase in extracellular concentrations of glutamate, dopamine, and GABA. At the dose of 4 mM, the increase of extracellular glutamate, dopamine, and GABA were 3.73 +/- 0.46 microM (n = 8; p < 0.001), 4.70 +/- 0.92 nM (n = 6; p < 0.001) and 0.36 +/- 0.08 microM (n = 8; p < 0.001), respectively. Perfusion of the NMDA-receptor antagonist CPP attenuated the increases of dopamine by 90% (n = 5; p < 0.001), but enhanced the increases of GABA by 70% (n = 7; p < 0.01). Perfusion of the AMPA-receptor antagonist DNQX did not attenuate the increases of GABA. These results suggest a differential mediation of ionotropic glutamatergic receptors in the actions of endogenous glutamate on extracellular concentration of dopamine and GABA.     

Evidence of basal pituitary-adrenal overactivity in first episode, drug naïve patients with schizophrenia

BACKGROUND: Evidence for basal hypothalamic-pituitary-adrenal (HPA) axis dysfunction in schizophrenia is less consistent than that seen in major depression. Potential reasons include sampling procedures and the use of patients on antipsychotic medications which may suppress the HPA axis. Therefore, the objective of this study was to determine whether first episode, drug na?ve patients with schizophrenia have evidence of basal HPA axis dysfunction by measuring plasma levels of AVP, ACTH and cortisol from 13:00 to 16:00 h, a time frame which is believed to reflect 24 h concentrations of HPA axis activity. METHOD: In this cross-sectional study, plasma levels of AVP, ACTH and cortisol were measured in 12 (7 males and 5 females) (mean age +/-SD=33.6+/-12.6 years) patients with DSM-IV schizophrenia and compared with those found in age- and sex-matched healthy controls. RESULTS: Patients and controls did not differ in terms of their 13:00 h cortisol and AVP. However, patients with schizophrenia had higher levels of ACTH as compared to control subjects at 13:00 h (41.3+/-14.6 vs. 12.4+/-1.1 pg/ml respectively; t=1.99, df=11, p <0.05). In comparison to controls subjects, patients with schizophrenia, had higher mean (+/-SE) AUC of ACTH (26.3+/-6.2 vs. 13.9 nmol/l, respectively; t=2.86, df=11, p <0.02) and cortisol (279.4+/-26.0 vs. 213.1+/-18.4 nmol/l, respectively; t=3.72, df=11, p <0.01). Though, patients with schizophrenia, in comparison to control subjects, had lower mean (+/-SE) AUC of AVP (0.87+/-0.24 vs. 1.42+/-0.34 pmol/l, respectively; t=2.29, df=11, p <0.02). CONCLUSIONS: First episode, drug na?ve patients with schizophrenia show evidence of basal overactivity of the pituitary-adrenal axis.     

GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum

BACKGROUND: Glutamic acid decarboxylase (GAD) is the rate limiting enzyme responsible for conversion of glutamate to gamma-aminobutyric acid (GABA) regulating levels of glutamate and GABA in the mammalian brain. Reelin is an extracellular matrix protein that helps in normal lamination of the embryonic brain and subserves synaptic plasticity in adult brain. Both GAD and Reelin are colocalized to the same GABAergic interneurons in several brain sites. We hypothesized that levels of GAD and Reelin would be altered in cerebellum of subjects with schizophrenia and mood disorders differentially vs. controls. METHODS: We employed SDS-PAGE and Western blotting to measure levels of GAD isomers 65 and 67 kDa and Reelin isoforms 410-, 330- and 180-kDa proteins as well as beta-actin in cerebellum of subjects with schizophrenia, bipolar disorder and major depression vs. controls (N = 15 per group). RESULTS: GAD 65- and 67-kDa levels were decreased significantly in bipolar, depressed and schizophrenic subjects (p < 0.05) vs. controls. Reelin 410- and 180-kDa proteins decreased significantly (p < 0.05) in bipolar subjects vs. controls. Reelin 180 kDa was decreased significantly (p < 0.05) in schizophrenics vs. controls. beta-Actin levels did not vary significantly between groups. There were no significant effects of confounding variables on levels of various proteins. CONCLUSION: This study demonstrates for the first time significant deficits in GABAergic markers Reelin and GAD 65 and 67 proteins in bipolar subjects and global deficits in the latter proteins in schizophrenia and mood disorders, accounting for the reported alterations in CSF/plasma levels of glutamate and GABA in these disorders.     

Diffusion tensor MRI and fiber tractography of cerebellar atrophy in phenytoin users

PURPOSE: The usefulness of diffusion tensor magnetic resonance imaging (DT-MRI) is still in debate, and the development of clinically feasible scan protocol is encouraged. The purpose of this study was to investigate the afferent fiber system to the cerebellum in patients with phenytoin (PHT)-induced cerebellar atrophy in comparison with cerebellar atrophy of other etiologies by using DT-MRI. METHODS: Thirteen patients (M/F ratio, 7:6; mean age, 42.5 years) and age-matched normal controls (n = 8) participated in this study. The patient group consisted of epilepsy patients who had received PHT therapy (n = 9) and clinically diagnosed as having olivopontocerebellar atrophy (OPCA; n = 4). DT-MRI was performed by using diffusion weighting of b = 600 s/mm2, and fractional anisotropy (FA) and color-coded vector maps were generated. FA of the middle cerebellar peduncle (MCP), the cerebellum, and transverse pontine fibers (TPF) was measured and compared between PHT and OPCA patients. RESULTS: Normal subjects showed FA values of 0.81 +/- 0.07 in MCP, 0.69 +/- 0.04 in TPF, and PHT users showed FA values of 0.84 +/- 0.09 in MCP, 0.72 +/- 0.08 in TPF, and 0.21 +/- 0.04 in cerebellum. OPCA patients showed FA values of 0.39 +/- 0.11 in MCP, 0.46 +/- 0.12 in TPF, and 0.22 +/- 0.07 in cerebellum. PHT users showed a statistically significant reduction of FA only in cerebellum, whereas OPCA demonstrated significant decrease of FA in MCP, TPF, and cerebellum (one-way analysis of variance, p < 0.01). Three-dimensional reconstruction of fiber tracts demonstrated decreased volume and altered fiber integrity within the peduncles and transverse pontine fibers in the OPCA group, whereas fiber course patterns in PHT users were similar to those in controls. CONCLUSIONS: PHT users showed normal orientation and anisotropy of MCP and TPF, whereas OPCA demonstrated impaired values, suggesting that PHT directly affects the cerebellum. DT-MRI can demonstrate detailed fiber configurations in degenerative diseases of brainstem and cerebellum and provides insight into the pathomechanisms of cerebellar atrophy.     

The relationship between GABA concentrations in brain and cerebrospinal fluid

GABA concentrations in cerebrospinal fluid (CSF) and brain of rats and cats were determined before and after intraperitoneal injection of three drugs that increase brain GABA levels. GABA exists in the CSF in two forms: free and conjugated GABA. In the CSF of untreated animals, there is very little free GABA (65 ± 12pmol/ml) but considerable amounts of conjugated GABA (2885 ± 100pmol/ml). After IP administration of γ-vinyl GABA to rats, CSF concentrations of both free and conjugated GABA rise in a dose-dependent manner. There is an exponential correlation (r = 0.92, P < 0.001) between rat whole brain GABA concentrations and free GABA in the CSF. Concentrations of brain GABA and conjugated CSF GABA are linearly correlated (r = 0.84, P < 0.001). γ-Acetylenic GABA has qualitatively similar effects to γ-vinyl GABA. Treatment with ethanolamine-O-sulfate i.p. at a dose not affecting brain GABA concentrations markedly increases serum GABA, leaves conjugated CSF GABA unchanged and significantly elevates free GABA in the CSF.These findings suggest that total CSF GABA concentrations are related primarily to brain GABA levels and are minimally affected by the changes in the peripheral GABA concentrations. Determination of the levels of free and conjugated GABA in the CSF may be useful for the estimation of brain GABA concentration in patients on therapy intended to alter brain GABA levels.     

Change in the concentrations of amino acids in CSF and serum of patients with essential tremor

Summary The concentrations of amino acids in the cerebrospinal fluid (CSF) (n=20) and serum (n=20) taken from patients with essential tremor were measured by HPLC and compared with those of controls (n=10). Reduced concentrations of some amino acids (asparagine, glutamine, glycine, threonine, isoleucine, leucine) were observed in serum taken from patients with tremor. Significant increases were detected in the concentrations of glutamate (p < 0.001) and aspartate (p < 0.01). The general tendency of the changes in CSF and serum was similar; although the highest differences were observed in amino acid concentrations in the serum of patients with essential tremor. Opposite shifts of some amino acids were detected, in the concentrations of aspartate, serine, tyrosine, leucine, and isoleucine, which may indicate the independence of the changes in the serum from those in the CSF. This study raises the possibility that a genetically determined metabolic disorder is involved in the etiology of essential tremor that appears peripherally and, partly, centrally. The slight increase in the concentration of glutamate together with the reduced levels of GABA, glycine, and serine in CSF may form the neurochemical basis of the central oscillation observed in essential tremor.     

Decreased levels of interleukin-10 and transforming growth factor-beta 2 in cerebrospinal fluid of patients with high grade astrocytoma

OBJECTIVE: Glioma cells can produce anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) which inhibit T cell and monocyte function. It is unknown if production of these cytokines is limited to the site of tumor or these molecules are also released to cerebrospinal fluid and blood. The goal of our study was to determine if patients with astrocytoma have increased levels of IL-10 and TGF-beta 2 in cerebrospinal fluid (CSF) and serum. METHODS: CSF and serum samples were taken from 16 patients with astrocytoma of grade III or grade IV according to the WHO classification and from 28 age- and gender-matched controls (patients with normal pressure hydrocephalus or with lumbar disk herniation). Cytokine concentrations were measured using ELISA methods. RESULTS AND DISCUSSION: There was no difference in serum levels of IL-10 and TGF-beta 2 between groups. Patients with astrocytoma had decreased levels of IL-10 (0.9 +/- 1.2 versus 3.5 +/- 9.2 pg/ml, p=0.01) and TGF-beta 2 (0.0 +/- 0.0 versus 5.4 +/- 9.4 pg/ml, p=0.05) in CSF compared to controls. Because serum IL-10 and TGF-beta 2 levels are similar in patients with astrocytoma and in controls, these cytokines are probably not directly involved in peripheral monocyte and T cell deactivation.