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)

Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance. After intravenous infusion of the keto analogues of valine, leucine, isoleucine, methionine and phenylalanine, the corresponding plasma amino acids, including alloisoleucine and tyrosine, rose sharply. Twenty-four hours later, fasting plasma ammonia had fallen from the preinfusion value of 0.050 to 0.028 mM. Protein intake was kept at 0.5 g per kilogram for two weeks. Addition of keto acids by mouth reduced plasma ammonia and alanine to normal or near normal levels. Seizures and episodes of vomiting and lethargy decreased in frequency. Urinary nitrogen decreased, suggesting that nitrogen balance improved. These data indicate that keto acids may be useful in the treatment of congenital hyperammonemia.
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PMID:Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. 16 4

To evaluate the effects of substrate deficiency on cerebral function, metabolism, and blood flow during seizures, rats were injected intravenously with bicuculline (1.2 mg.kg-1) following a 24-hour period of starvation. During the course of seizures, blood glucose concentrations fell, and when they were reduced to below about 3 mumol.gm-1, cerebral function, metabolism, and blood flow altered. Changes in function involved the transition of an electroencephalographic pattern of bursts and suppression into one of frequent or sparse single spikes. Oxygen consumption, which initially increased at least twofold, fell toward normal or subnormal values in the single-spike period. Cortical blood flow was markedly reduced, and there was an attenuated response to carbon dioxide administration. Simultaneously, a small but clear fall was detected in the cerebral phosphorylation potential, and concentrations of glycolytic metabolites (including lactate) and citric acid cycle intermediates were reduced. Changes in amino acids and ammonia were somewhat similar to those observed in insulin-induced hypoglycemia, but since the amino acid pool did not fall, the experiments failed to give evidence that amino acids serve as oxidative substrates. The perturbation of cerebral energy state (and of levels of carbohydrate substrates and amino acids) was reversed by glucose administration; but since neither this procedure nor additional bicuculline injections could cause resumption of continuous seizure activity, the results suggest that cellular substrate depletion may have given rise to a sustained disturbance of synaptic transmission.
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PMID:Effects of bicuculline-induced seizures on cerebral metabolism and circulation of rats rendered hypoglycemic by starvation. 42 77

Sustained, generalized seizure activity was induced in anaesthetized (70% N2O), paralyzed and artifically ventilated rats by i.p. DL-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations. Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occurring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine. Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF.
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PMID:Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine. 50 26

An ultrastructural study of cerebral cortex was performed in rats during the preictal period following the administration of the convulsant methionine sulfoximine (MSO). The morphologic changes were restricted to astrocytes and consisted of cytoplasmic enlargement, mitochondrial and rough endoplasmic reticulum proliferation, accumulation of glycogen, development of cisternal and saccular smooth endoplasmic reticulum, nuclear chromatin clumping, and hydropic degenerative changes. These findings resemble those seen in experimental ammonia encephalopathy, suggesting an important role of ammonia in the evolution of these morphologic changes. The findings, moreover, suggest that the primary effect of MSO is on astrocytes and that abnormalities in astrocytes may play a role in the development of MSO-induced seizures.
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PMID:Ultrastructural study of methionine sulfoximine-induced Alzheimer type II astrocytosis. 55 86

Infant rats, treated intracisternally with 6-hydroxydopamine or 5,7-dihydroxytryptamine, alone or in combination with desmethylimipramine or pargyline, at 5 to 7 days of age, had significant specific depletions of brain norepinephrine, dopamine, both of these amines, or serotonin at 2.5 months of age. Despite apparent long-term depletions of brain biogenic amines, susceptibility to audiogenically-induced seizures following chronic ethanol withdrawal in these animals was similar to that of controls. Amine-depleted rats also displayed spontaneous withdrawal-induced tremors, spastic motor activity and irritability. The interpretation of these preliminary findings with regard to the proposed role of the biogenic amines in the development of physical dependence on ethanol is discussed.
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PMID:Effects of 6-hydroxydopamine or 5,7-dihydroxy-tryptamine on the development of physical dependence on ethanol. 56 50

Reye's syndrome in infancy is not a well-defined entity and is infrequently diagnosed. Eight infants 6 months of age or younger had a prodromal viral illness followed by the rapid onset of lethargy, seizures, and coma, resulting in the diagnosis of Reye's syndrome. All had abnormal results of liver function tests including elevations of blood ammonia level. Three patients had pathological studies that confirmed fatty visceral infiltration. The data on these patients, as well as a review of the literature, indicate that the most prominent clinical findings in Reye's syndrome in infancy include marked respiratory abnormalities with tachypnea and apneic episodes; frequent occurrence of seizures in the early stages of the illness; and hypoglycemia in most cases. A strong socioeconomic bias was noted in these patients, with the infants coming primarily from lower socioeconomic, urban environments, while older children with Reye's syndrome have been observed to be predominantly middle-class and from suburban or rural areas.
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PMID:Reye's syndrome in infancy. 68 88

The blood ammonia levels were estimated in 42 children with convulsions (grand mal). The levels were elevated within 3 hours after the seizure without exception (23 children). 4 to 8 hours after the seizure the levels were found near the upper norm range (6 children). The levels returned to normal 24 hours after the seizure (13 children).
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PMID:Postconvulsivant hyperammonaemia (author's transl). 81 16

The hospital course and therapy of 369 patients with Reye's syndrome were evaluated. Eighty-three percent of patients had deepening coma during hospitalization. Stage of coma on admission, evidence of increased intracranial pressure, and blood ammonia levels greater than 300 microgram/100 ml were all significantly associated with increasing mortality. Among survivors of Reye's syndrome, 30% of those who developed either decerebrate posturing or seizures during hospitalization had serious neurologic sequelae upon discharge. When analyzed by (1) stage of coma during admission (2) progression of coma during hospitalization, (3) degree of blood ammonia level elevation, and (4) presence of increased intracranial pressuring, no significant differences were noted between patients receiving intensive supportive care and those receiving exchange transfusions and/or peritoneal dialysis.
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PMID:Reye's syndrome: clinical progression and evaluation of therapy. 91 33

A light microscopic study was performed during the preictal period following the administration of methionine sulfoximine (MSO) to adult rats. The principal morphologic observation was the development of Alzheimer II astrocytes in gray matter, suggesting that the metabolic abnormality induced by MSO is initially confined to the astrocyte. In view of the association of the Aizheimer II astrocyte with hyperammonemic states, the drug toxicity may be secondary to the presence of ammonia. A possible mechanism involves astrocytes in the development of seizures produced by MSO.
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PMID:Alzheimer II astrocytosis following methionine sulfoximine. 116 49

Subacute necrotizing encephalopathy (Leigh syndrome) is characterized by lactacidosis, seizures, ataxia, multiple cerebral hypervascularized lesions and mitochondrial oxidation defects. This is a report on a 21-year-old patient with proven Leigh syndrome, mild central and provokable peripheral lactacidosis, an extra-erythrocyte complex II defect, functionally reduced myokinase adenylate deaminase activity, but no ultrastructural mitochondrial changes. Determination of lactate, pyruvate and ammonia under ischemic conditions plus a pyruvate loading test were particularly useful. Oral flunarizine (Sibelium 30 mg/d) proved to be therapeutically effective.
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PMID:Diagnosis and treatment in a case of juvenile subacute necrotizing encephalopathy Leigh without cytochrome c oxidase deficiency. 132 78


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