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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A conceptual approach to the understanding of the pathogenesis of idiopathic seizures is presented. Hypokalemia and/or alkalosis promotes the elaboration of an alkaline urine, which increases the renal return of ammonia and exposes the brain to chronically higher concentrations of ammonia. In the brain, ammonia is preferentially detoxified to glutamine and therefore depletes the available glutamic acid, which is also a precursor of GABA, the major mediator of central inhibition. Mild chronic elevations of ammonia may also result in long-term nutritional alterations of amino-acid precursors of other brain neurotransmitters. A linkage thus exists for the metabolic basis of seizures: the role of the potassium-ammonia axis may be important in the selective depletion of GABA, the major mediator of central inhibition.
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PMID:The metabolic basis for the genesis of seizures: the role of the potassium-ammonia axis. 671 22

Seventeen patients with partial epilepsy had electroencephalographic (EEG) monitoring concurrent with cerebral positron emission computed tomography (PECT) after 18F-fluorodeoxyglucose (18FDG) and 13N-ammonia (13NH3) were given intravenously as indicators of local cerebral glucose utilization (LCMRglc) and relative perfusion, respectively. In 12 of 15 patients who had unilateral or focal electrical abnormalities, interictal 18FDG scan patterns clearly showed localized regions of decreased (14 to 58%) LCMRglc that correlated anatomically with the eventual EEG localization. These hypometabolic zones appeared normal on x-ray computed tomography in all but 3 patients and were unchanged on 18FDG scans repeated on different days. In 5 of 6 patients who underwent anterior temporal lobectomy the interictal 18FDG scan correctly detected the pathologically confirmed lesion as a hypometabolic zone, and removal of the lesion site resulted in marked clinical improvement. In contrast, the ictal 18FDG scan patterns clearly showed foci of increased (82 to 130%) LCMRglc that correlated temporally and anatomically with ictal EEG spike foci and were within the zones of interictal hypometabolism (three studies in 2 patients). 13NH3 distributions paralleled 18FDG increases and decreases in abnormal zones, but 13NH3 differences were of lesser magnitude. When the relationship of 13NH3 uptake to local blood flow found in dog brain was applied as a correction to the patients' 13NH3 scan data, local alterations in perfusion and glucose utilization were usually matched in both the interictal and the ictal state. We conclude that the interictal 18FDG-PECT scan is useful in aiding localization of the dysfunctional cerebral zone most likely to be responsible for seizures in patients being considered for anterior temporal lobectomy. With further development, emission computed tomography may help in better categorizing the various forms of the disorder and in elucidating the basic mechanisms of epilepsy in humans.
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PMID:Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3. 677 78

Shortly after birth, a newborn girl developed anorexia, hypotonia, apneic attacks and seizures. After 61 h the child died in coma. Biochemically, a highly elevated blood ammonia level was found together with an increased plasma level of the amino acids mainly involved in ammonia detoxication. Enzyme studies in post-mortem liver tissue material revealed a deficiency of carbamoyl-phosphate synthetase (0.9% of the mean value in controls) in combination with an intermediate activity of L-ornithine: 2-oxoglutarate aminotransferase (40% of the mean value in controls).
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PMID:A lethal neonatal variant of carbamoyl-phosphate synthetase deficiency in combination with an intermediate activity of L-ornithine: 2-oxoglutarate amino-transferase. 685 Dec 28

Two preterm infants had serum ammonia levels of 2400 and 2800 micrograms per deciliter and profound neurologic depression with seizures and coma. Both responded to treatment by exchange transfusion and peritoneal dialysis. All previously reported survivors of transient hyperammonemia of the preterm infant have had normal neurologic and developmental examinations on follow-up.
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PMID:Transient hyperammonemia in the preterm infant: neurologic aspects. 719 96

Central pontine myelinolysis (CPM) is a demyelinating condition of the central pons with or without associated foci of demyelination in extrapontine areas. We present a case of partial ornithine carbamoyl transferase deficiency in a 5-year-old girl which was complicated by CPM. The patient was a previously undiagnosed girl who presented with mild hyperammonemic encephalopathy with a maximum plasma ammonia level of 376 microM on admission. Laboratory testing established the diagnosis of OCT deficiency, and therapy with hydration and protein restriction was successful in returning the plasma ammonia levels to normal. Five days after correction of her hyperammonemia, the patient developed intractable seizures and coma. Serial MRI scans of the brain revealed the evolution of the characteristic findings of CPM. Plasma ammonia and electrolyte concentrations were well controlled throughout this time. This represents the first description of CPM in a patient with a urea cycle defect.
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PMID:Central pontine myelinolysis as a complication of partial ornithine carbamoyl transferase deficiency. 757 73

Contact activation of the intrinsic pathway of porcine blood plasma coagulation is shown to be a steep exponential-like function of procoagulant surface energy, with low activation observed for poorly water-wettable surfaces and very high activation for fully water-wettable surfaces. Test procoagulants studied were a system of oxidized polystyrene films with varying wettability (surface energy) and glass discs bearing close-packed self-assembled silane monolayers (SAMs) with well-defined chemistry consisting of 12 different terminating chemical functionalities. A monotonic trend of increasing coagulation activation with increasing water wettability was observed for the oxidized polystyrene system whereas results with SAM procoagulants suggested a level of chemical specificity over and above the surface energy trend. In particular, it was noted that coagulation activation by SAMs terminated with--CO2H was much higher than anticipated based on surface wettability whereas--NH3(+)-terminated SAMs exhibited very low procoagulant activity. SAMs terminated in--(CH2)2(CF2)7CF3 behaved as anticipated based on surface energy with very low procoagulant activity and did not exhibit special properties sometimes attributed to perfluorinated compounds. Quantitative ranking of the inherent coagulation activation properties of procoagulant surfaces was obtained by application of a straightforward phenomenological model expressed in a closed-form mathematical equation relating coagulation time to procoagulant surface area. Fit of the model with a single adjustable parameter to experimental measurements of porcine platelet-poor plasma coagulation time was very good, implying that assertions and simplifications of the model adequately simulated reality. Two important propositions of the model were that (1) the number of putative "activating sites" scaled linearly with procoagulant surface area, and (2) contact activation of the plasma coagulation cascade was catalytic in the sense that these activating sites were not consumed or "poisoned" by irreversible or slowly reversible protein adsorption during coagulation. An extension of the coagulation model proposed that procoagulant activation properties scale exponentially with the surface density of polar (acid-base) sites, which, in turn, was related to procoagulant wettability.
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PMID:Contact activation of the plasma coagulation cascade. I. Procoagulant surface chemistry and energy. 759 31

Eleven substituted 8-amino-3-benzyl-1,2,4-triazolo[4,3-a] pyrazines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. The compounds were prepared in four stages from the phenylacetonitriles. I. The intermediate (2,2,2-triethoxyethyl)benzenes III were condensed with 2-chloro-3-hydrazinopyrazine (IV) to provide the 3-benzyl-8-chloro-1,2,4-triazolo[4,3-a]pyrazines V. The latter were converted to the 8-amine targets VI with methylamine or ammonia. Several compounds exhibited potent activity against MES; the 3-(2-fluorobenzyl)-8-(methylamino) and 3-(2,6-difluorobenzyl)-8-(methylamino)congeners (4 and 12) exhibited the best anticonvulsant activity with oral ED50S of 3 mg/kg. The 1,2,4-triazolo[4,3-a]pyrazine ring system serves as a bioisostere of the purine ring for anticonvulsant activity; however, these agents exhibit less propensity to cause emesis.
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PMID:8-Amino-3-benzyl-1,2,4-triazolo[4,3-a]pyrazines. Synthesis and anticonvulsant activity. 765 56

A 4.5-year-old boy with chronic progressive encephalopathy is described. The clinical presentation initially included seizures and hypotonia which later evolved into severe extrapyramidal disease and dementia. The gas chromatography/mass spectrometry (GC/MS) analysis of urine indicated that alpha-ketoglutarate was increased 210 times and aconitic acid 80 times. No disturbance of acid/base balance, lactic acid or ammonia metabolism accompanied this clinical picture. The fibroblasts contained 29% of normal alpha-ketoglutarate dehydrogenase activity, while the activity of another mitochondrial marker enzyme, glutamate dehydrogenase, was normal. The neuroimaging studies revealed bilateral striatal necrosis. The clinical and biochemical findings were almost identical to two previously reported patients. Experience with this patient emphasizes the need for detailed organic acid biochemical investigation in any progressive encephalopathy and that extrapyramidal tract signs should evoke the possibility of alpha-ketoglutaric aciduria, among other 'neurologic organic acidemias'.
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PMID:A new patient with alpha-ketoglutaric aciduria and progressive extrapyramidal tract disease. 772 79

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.
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PMID:Protection of the brain by carnitine. 774 96

Congenital ornithine transcarbamylase (OTC) deficiency in humans is associated with seizures and mental retardation. As part of a series of studies to delineate the neurochemical features of OTC deficiency, activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), respectively, were measured in brain regions of the congenitally hyperammonemic sparse-fur (spf) mouse, a mutant with an X-linked inherited defect of OTC. ChAT activities were reduced by 63% (P < 0.01) in cerebral cortex of spf mice compared with CD-1/Y controls. Activities of the GABA nerve terminal marker enzyme, glutamic acid decarboxylase, on the other hand, were within normal limits. Using an immunohistochemical technique with a monoclonal antibody to ChAT, a significant loss of ChAT-positive neurons was observed throughout the cerebral cortex, septal area and diagonal band of spf mice. These results suggest that a loss of forebrain cholinergic neurons is a feature of congenital OTC deficiency in these mutants. Possible pathogenetic mechanisms responsible for the cholinergic neuronal loss in congenital OTC deficiency include neurotoxic effects of ammonia and accumulation of quinolinic acid.
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PMID:Evidence for cholinergic neuronal loss in brain in congenital ornithine transcarbamylase deficiency. 781 42


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