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)

Clinically, patients with Delirium Tremens (DT) and acute alcohol hallucinosis (impending DT) appear excited with vivid false perception. Cerebral blood flow and eeg correspondingly point to hyperexcitability in the CNS during these conditions. Clinical trials with barbital treatment in alcohol withdrawal shows that the amount of drug and the drug plasma concentration is the same no matter whether the physical signs of withdrawal are accompanied by hallucinations and clouding of consciousness. The psychotic signs in DT and acute alcoholic hallucinosis develops after many years of alcoholism as does seizures. We hypothesize that physical withdrawal is determined by the degree of physical dependence developed during the most recent drinking period whereas the psychotic signs and seizures are due to a cumulated CNS hyperactivity developed over many years of repeated alcohol intoxication and withdrawal. Changes of electrolyte concentrations in plasma or CSF do not play an important role in the pathogenesis of DT and related clinical states except that changes in calcium and inorganic phosphate metabolism indirectly point to changes in membrane excitability. A new model for a study of rapidly repeated intoxication and withdrawal episodes in rats has shown that repetition of episodes augments the convulsive component of withdrawal whereas the non-convulsive signs are dependent on the most recent episode only. The augmentation of the convulsive component correlates with regional differences in brain glucose consumption. Furthermore, synaptic proteins and acidic phospholipids may be involved in the development of CNS hyperexcitability during alcohol withdrawal. In conclusion both clinical and experimental studies indicate that severe alcohol withdrawal reactions may consist of two components: 1) Physical withdrawal signs determined by recent physical dependence. 2) A long term cumulated CNS hyperexcitability relating to seizures and psychotic signs during withdrawal. This state is elicited by alcohol withdrawal but it represents a cumulated and permanent or long lasting CNS dysfunction in alcoholics. The precise biochemical/pathophysiological mechanisms for the development of the two-component dysfunction still remain to be clarified in detail.
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PMID:Delirium tremens and related clinical states: psychopathology, cerebral pathophysiology and psychochemistry: a two-component hypothesis concerning etiology and pathogenesis. 306 44

The cerebral metabolic response to bicuculline (BC)-induced status epilepticus (SE) was studied in two-week-old ketamine-anesthetized marmoset monkeys. During 30-min clonic seizures, mean blood pressure, plasma glucose and paO2 did not decrease and plasma lactate doubled. Brains were funnel-frozen and punch biopsies of frontoparietal cortex, temporal cortex and thalamus were analyzed for ATP, phosphocreatine (PCr), glucose and lactate. There were marked reductions of ATP (to 56-77% of controls), PCr (to 23-28% of controls) and glucose (to 1-4% of controls), and lactate increased 3- to 6-fold in seizure animals. NADH fluorescence increased during seizures in cerebral cortex, thalamus, amygdaloid nuclei, hippocampus, posterior striatum and hemispheric white matter. This suggests a reduced tissue redox state in these regions and is correlated with the high energy phosphate depletion and elevated lactate in cortex and thalamus. Our results demonstrate a significant depletion of energy reserves and glucose in cerebral cortex and thalamus during neonatal seizures in the absence of adverse systemic factors. These seizure-induced metabolic changes in brain could have adverse long-term effects on brain development and function.
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PMID:Generalized seizures deplete brain energy reserves in normoxemic newborn monkeys. 313 58

Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels were measured in rats following experimental traumatic brain injury. Rats (n = 36) were prepared for fluid percussion brain injury under pentobarbital anesthesia. Twenty-four hours later, rats were lightly anesthetized using methoxyflurane, injured (2.3 atm), and killed 5 or 15 min later. Twelve of the rats died before and are not included in the analyses. The following groups were used for data analysis: group I (n = 6) were sham-injured rats prepared for injury but not injured: group II (n = 6) were injured and killed 5 min later; group III (n = 12) were injured and killed 15 min posttrauma. Thirty seconds prior to sacrifice by decapitation into liquid nitrogen, all rats were injected with indomethacin (3 mg/kg, intravenously [IV]) to prevent postmortem PG synthesis. After sacrifice, brains were removed, weighed, and homogenized in a small quantity of phosphate buffer with indomethacin (50 micrograms/ml). PGE2 and TxB2 levels were determined using double-label radioimmunoassays. Posttraumatic convulsions were observed in 5 of 12 rats in group III and these rats were analyzed separately. PGE2 and TxB2 levels increased significantly (p less than 0.05) in both hemisphere and brainstem 5 min posttrauma. Fifteen minutes after injury, both PGE2 and TxB2 levels remained elevated but the levels were lower than at 5 min in the rats that did not exhibit posttraumatic seizures. This decrease in PG levels at 15 min was not observed in the rats that had seizures after injury and both PGE2 and TxB2 levels remained high in hemispheres and brainstem. Thus, fluid percussion brain injury results in substantial elevations in PGE2 and TxB2 levels and posttraumatic seizures exacerbate the observed increases.
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PMID:Experimental traumatic brain injury elevates brain prostaglandin E2 and thromboxane B2 levels in rats. 324 9

The dialysis encephalopathy syndrome is at once the most widely recognized and most severe manifestation of aluminum toxicity. Evidence linking this syndrome and aluminum intoxication is virtually incontrovertible. The syndrome is characterized by speech and motor difficulties, dementia, and seizures. Less widely recognized symptoms include subtle changes in cognition and personality and directional disorientation. Since the widespread use of water treatment, aluminum exposure in the dialysis population has been primarily via intravenous (IV) medications and oral aluminum-containing, phosphate-binding antacid gels. In addition to the encephalopathy syndrome, aluminum has been linked to toxicity in bone, parathyroid gland, RBC, and kidney. These organ toxicities seem to be the result of specific protein enzyme inhibition. Currently identified factors that affect aluminum accumulation and modulate aluminum balance include uremia, renal function, parathyroid hormone withdrawal and suppression, 1,25-dihydroxycholecalciferol, and serum aluminum binding. Impaired renal function is not a prerequisite for increased tissue aluminum burdens. It is likely that aluminum-related disease will be increasingly observed in populations other than those with chronic renal failure.
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PMID:The metabolism of aluminum and aluminum-related encephalopathy. 329 87

Seizures in renal transplant recipients may be due to a variety of causes. Although intravenous pulse methylprednisolone used to treat acute rejection episodes has been reported to be associated with acute central nervous system (CNS) manifestations in adult renal transplant patients, this complication has not previously been described in pediatric patients. We report a 12 year old renal transplant recipient who developed transient blindness and focal seizures 72 hours following intravenous pulse methylprednisolone. Serum creatinine and urea nitrogen were 1.5 and 31 mg/dl respectively; serum electrolytes, calcium, magnesium, phosphate, and glucose were normal. Although usually due to other etiologies, seizures in the pediatric transplant recipient may be secondary to acute CNS toxicity resulting from intravenous glucocorticoid infusion.
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PMID:Seizures and blindness following intravenous pulse methylprednisolone in a renal transplant patient. 330 30

Noninvasive NMR spectroscopy of 1H, 31P, and 23Na is performed simultaneously to study brain metabolism during grand mal seizures. Decreases in PCr and increases in lactate associated with seizure as well as an intracellular shift of the Na+ ion pool are demonstrated. A close correlation between the phosphate potential and the intensity of the seizure, as well as the intra/extracellular ionic gradient, is shown.
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PMID:Triple nuclear NMR studies of cerebral metabolism during generalized seizure. 335 2

Biochemical and pharmacological effects of gamma-vinyl GABA (Vigabatrin, GVG), and irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- and dose-dependent elevation of the GABA, phenylalanine and lysine contents of cortical tissue and simultaneously decreased glutamate, aspartate and alanine levels. In addition, GVG caused a biphasic change in glutamine concentrations (a decline 1-4 hours after administration, followed 20 hours later by an increase). Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column. The level of this novel chemical entity was greatly increased by GVG 20 hours after injection of the drug. At all tested intervals between 1 and 60 hours after injection, GVG was ineffective against maximal electroshock. The GABA-T inhibitor dose-dependently protected mice against isoniazid-induced seizures, simultaneously causing an increase in brain GABA concentrations. However, this apparent correlation applied only until 4 hours after treatment. To better define the anticonvulsant profile of GVG, groups of mice were treated, 1, 2, 4, and 24 hours prior to challenge with convulsant doses of strychnine, pentetrazole (PTZ), and picrotoxin, and brain amino acid levels, including brain concentrations of GVG, were measured. In all instances, the time dependency of the anticonvulsant effects of GVG and of increases in brain GABA levels differed. Amino acid concentrations in animals treated only with GVG were similar to those in animals given GVG and a chemical convulsant. GVG showed no selectivity for seizures produced by impairment of GABA-ergic neurotransmission. Although GVG is an effective GABA-T inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts with other neurotransmitter systems as well.
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PMID:Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. 341 34

Rats treated intravenously with an organophosphorus anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7 sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucose as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8 LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2 hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.
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PMID:Cerebral metabolic effects of organophosphorus anticholinesterase compounds. 350 39

In vivo [31P] nuclear magnetic resonance (NMR) spectroscopy disclosed that a 10 second electroshock seizure in oxygenated neonatal dogs produced prolonged alteration of brain phosphocreatine (PCr), inorganic phosphate (Pi), and lactate. The slow return of these metabolites to baseline may be related to lower endogenous stores of high energy phosphates, or less developed pathways for their regeneration.
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PMID:Brain metabolism after electroshock seizure in the neonatal dog: a [31P]NMR study. 356 76

The authors report a new form of metaphyseal chondrodysplasia revealed in a 5 1/2 year-old boy with seizures. This disorder associated coxa vara, large terminal phalanges, bilateral cataracts and severe mental deficiency. Both parents were healthy, suggesting autosomal recessive transmission. There is no associated calcium phosphate metabolism disorder. An enzymatic abnormality might be the cause of the bone, ocular and neuronal lesions.
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PMID:[A new form of metaphyseal chondrodysplasia]. 357 65


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