Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of L-5-hydroxytryptophan (5-HTP) on the threshold for maximal electroconvulsions was compared with concomitant changes in levels of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in plasma and brain of rats. A single injection of 5-HTP (100 mg/kg, i.p.) caused significant elevation in seizure threshold which was markedly intensified by pretreatment with the decarboxylase inhibitor carbidopa (10 mg/kg, i.p., 0.5 hr previously). Pretreatment with carbidopa also resulted in behavioural changes, i.e. the characteristic "wet-dog shake" behaviour became much more prominent. Biochemically, administration of 5-HTP gave rise to significant elevation of levels of 5-HTP, 5-HT and 5-HIAA in plasma and brain. Carbidopa increased levels of 5-HTP in the brain, decreased 5-HIAA in the periphery but did not alter the elimination rate of 5-HTP in plasma. In both naive rats and rats pretreated with carbidopa, a significant correlation was found between levels of 5-HTP and 5-HIAA in plasma and brain following injection of 5-HTP. Furthermore, in the absence of carbidopa, the increases of levels of 5-HT in plasma and brain induced by 5-HTP were correlated in a significant fashion. When the changes in the electroconvulsive threshold were compared with respective changes in levels of 5-hydroxyindoles, a significant correlation was obtained between threshold elevations and increases of 5-HTP and 5-HT in the brain. In rats treated with 5-HTP, without decarboxylase inhibitor, a significant correlation was found between increases in 5-HT in plasma and the seizure threshold. The results suggest that analysis of 5-hydroxyindoles in plasma may represent a useful tool for the estimation of 5-HT metabolism in brain.
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PMID:L-5-hydroxytryptophan. Correlation between anticonvulsant effect and increases in levels of 5-hydroxyindoles in plasma and brain. 608 1

Clinical picture of neuronal ceroid lipofuscinosis with late infantile onset (LINCL) is characterized by myoclonic seizures and psychomotor regression. We present a case of classic LINCL and reduced cerebrospinal fluid (CSF) pterins in a girl of normal psychomotor development and born to non-consanguineous parents. She first presented with febrile seizures at the age of four. At that time, brain computed tomography finding was normal, but electroencephalogram showed hypsarrhythmia. At the age of five, tremor, generalized ataxia, and motor and mental regression appeared. Brain magnetic resonance imaging showed cerebellar atrophy. Electron microscopy examination showed storage of intracytoplasmic curvilinear inclusions in neurons, fibroblasts, and secretory cells of the skin and rectal mucosa. Tripeptidyl peptidase I (TPP-I) activity in leukocytes was very low (5.4 nmol/h/mg protein; range in homozygote cases of LINCL, 0.4-26.0). Molecular genetic studies showed a homozygous mutation, R208X, in exon 6 of CLN2 gene. CSF analysis revealed very low neopterin (7.3 nmol/L; normal range, 9-30) and biopterin (4.1 nmol/L; normal range, 10-30), reduced homovanillic acid (266 nmol/L; normal range, 211-871), and low homovanillic acid/5-hydroxyindoleacetic acid ratio (1.21; normal ratio, 1.5-3.5). Treatment with L-Dopa/Carbidopa (4 mg/kg) and antiepileptics was introduced, but without significant effect. It seems that low CSF pterins and impaired dopamine turnover are secondary manifestations of classical LINCL caused by homozygous inheritance of the R208X mutation in CLN2 gene.
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PMID:R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis. 1295 Jan 56

We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities.
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PMID:Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target? 2918 79