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Aim: To determine the prevalence of dopaminergic abnormalities in 1388 children with neurological disorders, and to analyse their clinical, neuroradiological, and electrophysiological characteristics., Method: We studied biogenic amines in 1388 cerebrospinal fluid (CSF) samples from children with neurological disorders (mean age 3y 10mo, SD 4y 5mo; 712 males, 676 females. Correlations among CSF homovanillic acid (HVA) values and other biochemical, clinical, neuroradiological, and electrophysiological parameters were analysed., Results: Twenty-one patients with primary dopaminergic deficiencies were identified. Of the whole sample, 20% showed altered HVA. We report neurological diseases with abnormal CSF HVA values such as pontocerebellar hypoplasia, perinatal asphyxia, central nervous system infections, mitochondrial disorders, and other genetic diseases. Overlapping HVA levels between primary and secondary dopamine deficiencies were observed. Prevalence of low CSF HVA levels was significantly higher in neonatal patients (χ(2) =84.8, p<0.001). Abnormalities in white matter were associated with low CSF HVA (odds ratio 2.3, 95% confidence interval 1.5-3.5)., Interpretation: HVA abnormalities are observed in various neurological diseases, but some are probably an unspecific finding. No clear limits for CSF HVA values pointing towards primary diseases can be stated. We report several neurological diseases showing HVA alterations. No neuroimaging traits were associated with low HVA values, except for white matter abnormalities., (© The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.)

Background: The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects., Patients and Methods: CSF amine related compound levels and thiamine results were compared in 40 FA, 44 OPCA and nine ARSAC patients with those of 94 sex- and age-matched subjects. Neuroimaging (CT scans and single photon emission computed tomographies i.e. SPECT) were carried out in all patients and controls. Genetic studies were conducted on OPCA patients. CSF amine related compounds were measured by high performance liquid chromatography, whereas CSF thiamine levels were measured by a microbiological method., Results: FA patients had significantly lower CSF HVA, 5HIAA and thiamine values than control patients and a trend for lower MHPG levels. In OPCA patients, CSF HVA, MHPG and thiamine values were markedly lower whereas CSF 5HIAA values showed only a trend towards lower levels; in ARSAC patients only thiamine and HVA CSF values were lower than those in control subjects., Conclusion: After presenting the relationships between neurochemical findings on one side, the degree of ataxia, the degree of cerebellar atrophy and the SPECT findings on the other, the authors concluded that replacement and neuroprotective clinical trials in these patients would have to include two or three drugs because the neurotransmitter deficiencies are multiple.

In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well-characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743 +/- 1,661 ng/L; mean +/- SD) and AD (346 +/- 176 ng/L) compared with controls (138 +/- 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 +/- 237 ng/L) than those with signs of upper motor neuron disease (2,435 +/- 1,633 ng/L) (p < 0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 +/- 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.

We have studied an effect of cerebrospinal fluid (CSF) from patients with amyotrophic lateral sclerosis (ALS) on explanted and dissociated ventral spinal cord cultures from 13-day-old rat embryos. CSF samples were obtained from 10 ALS patients, 10 other neurological patients, and 10 non-neurological patients. CSF was added at dilution of 10, 25, and 50%. Neurite length and neuronal survival ratio were not significantly different among these three groups. ALS CSF does not contain a neurotoxic factor on the cultured spinal motor neurons.

Measurement of monoamine metabolites in cerebrospinal fluid (CSF) has been one of the few methods available to study monoamine transmitter function in the human central nervous system (CNS). It has steadily proved to be of much use in clinical research of neurological and psychiatric diseases, in which altered functions of central monoamine neurotransmitters have been identified. In this work 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were quantified in normal CSF and in patients with untreated Parkinson's disease (PD) and olivopontocerebellar atrophy (OPCA). Normal CSF was obtained from 162 patients at the time of spinal anesthesia for surgery. Reference values for monoamine metabolites were established for normal adult lumbar CSF. Up to the age of 70 years no relation of monoamine metabolite concentration with age or sex were encountered. In individuals above 70 years of age higher levels of MHPG, HVA, and 5-HIAA were present in women, while in men only higher levels of MHPG could be detected. A strong correlation between 5-HIAA and HVA concentrations were observed in all groups. PD patients exhibited normal CSF metabolite levels, but an altered 5-HIAA/HVA ratio, favoring 5-HIAA. Dominant and recessive OPCA differed essentially in HVA concentration-diminished in the first group and elevated in the last. Comparing the results obtained in PD and dominant OPCA, we suggest that the decrease of CSF HVA in the latter group might not reflect nigrostriatal degeneration as we previously thought. Possibly another factor influencing dopamine function in the CNS is involved.

The modifications in the CSF content of glutamate and GABA in patients afflicted with primary degenerative dementia (PDD) and olivo-ponto-cerebellar atrophy (OPCA) have been evaluated. Control subjects (with disk herniation) were also included in the study. The amino-acids assays were carried out utilizing enzymatic-bioluminescence technique. GABA levels in controls were 803 +/- 98 (n = 7) and in demented patients 702 +/- 98 (n = 7) pmol/ml. Glutamate levels were 2067 +/- 244 (n = 10) in controls, 1190 +/- 81 (n = 16) pmol/ml (vs controls p less than 0.01) in demented patients, and 1116 +/- 146 (vs controls p less than 0.01) in OPCA patients. These results suggest that CSF glutamate levels in severely demented patients might be a result of generalized neuronal loss in the brain with a reactive gliosis.

Blood thiamine levels in ataxia patients were studied. No significant differences were found between 30 patients with Friedreich's ataxia and 29 patients with olivopontocerebellar atrophy (OPCA) compared with control subjects. Both OPCA and Friedreich's ataxia patients presented significantly lower cerebrospinal fluid thiamine levels than their controls (p less than 0.001 and p less than 0.04 respectively). These results, discussed in terms of the high degree of cerebellar atrophy on CT scans in OPCA v Friedreich's ataxia patients, seem to correlate with cerebellar thiamine turnover and content.

Idiopathic chronic autonomic dysfunction may occur as pure autonomic failure (PAF) or in association with multiple system atrophy (MSA). CSF immunoreactivity to rat locus ceruleus occurred in a significantly greater number of samples from MSA patients compared to control subjects or patients with PAF. Other brain regions infrequently showed immunoreactivity. These findings suggest that degeneration in MSA may release antigen(s) that induce antibodies against locus ceruleus neurons. Further studies are required to determine whether immune abnormalities play a pathogenetic role in MSA. Lack of CSF immunoreactivity in PAF is consistent with primarily peripheral involvement.

Amantadine hydrochloride (AH) was administered (200 mg/day) for more than three months to 17 patients with Friedreich's ataxia (FA) and to 12 patients with olivopontocerebellar atrophies (OPCA) in an open clinical trial. Reaction time (RT) and movement time (MT) with the right and left hand were measured before and after treatment. A striking improvement on both RT and MT was observed in the OPCA group (on seven out of eight measures), whereas in the FA patients improvement was seen only in two out of four MT measures with no improvement in RT. Both groups had low levels of homovanillic acid (HVA) in their cerebrospinal fluid before treatment, relative to their controls. However, improvement with AH was not related to HVA levels.

We evaluated the concentrations of the putative transmitter amino acids in the cerebrospinal fluid, and found a significant reduction of glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine concentrations in parkinsonian patients. There was no difference in amino acid concentrations between parkinsonian patients receiving L-DOPA and those not receiving L-DOPA. A similar decrease of glutamate and aspartate concentrations was found in patients with spinocerebellar degeneration. Concentrations of asparagine, glycine and taurine were also significantly decreased in patients with late cortical cerebellar atrophy.

Low lumbar CSF concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in patients with multiple system atrophy attended by autonomic failure (MSA) reflect decreased activity in central dopaminergic and serotonergic pathways. These neurochemical changes are consistent with the neuropathological involvement in MSA and distinguish such patients from those with pure autonomic failure who have normal CSF metabolite levels.