Epilepsy research
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The anticonvulsant topiramate is effective in laboratory animals against maximal electroshock seizures, amygdala kindling, and spike-wave discharges and has demonstrated efficacy in humans for the treatment of complex partial seizures. However, its mechanism of action has yet to be clearly elucidated. When the chloride-sensitive fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) was used as a tool for estimating the effect of anticonvulsant drugs on GABA receptor function, topiramate was observed to enhance GABA-stimulated chloride (Cl-) flux. ⋯ In vivo anticonvulsant studies confirmed that topiramate, like phenytoin, is primarily effective against tonic extension seizures induced by maximal electroshock and is ineffective against clonic seizures induced by the subcutaneously administered chemoconvulsants pentylenetetrazol (PTZ), bicuculline (Bic), and picrotoxin (Pic). In contrast to phenytoin, topiramate, at a dose equivalent to the MES median effective dose (ED50), was found to elevate seizure threshold as estimated by the intravenous PTZ seizure threshold test. Taken together these results support the conclusion that enhancement of GABA-mediated Cl- flux may represent one mechanism that contributes to the anticonvulsant activity of topiramate.
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Acute audiogenic seizures are a model of generalized tonic-clonic seizures, induced by high intensity acoustic stimulation in genetically susceptible rodents. The neural substrate are sensory motor brainstem nuclei. Recruitment of forebrain structures takes places upon repetition of acoustically evoked seizures. ⋯ In conclusion, audiogenic kindling effectively recruits forebrain structures, responsible for the appearance of limbic seizures. It is possible that the paradigm used in group I was subthreshold for the development of clear-cut synaptic reorganization in the hippocampal mossy fiber system, since the behavioral patterns reverted ten days after the last seizure induction. In group II, however, an increased number of evoked seizures and a more prolonged time after the last chronic seizure showed structural re-arrangements in amygdala, perirhinal cortex and hippocampus, associated with permanence in terms of behavioral data (lack of regression of limbic seizures to control values).
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After the case report H. M. [42], unilateral neurosurgical interventions in the mediotemporal area have no longer been performed, if damage to the contralateral mediotemporal region was present, because of running the risk of provoking a postoperative amnesic syndrome. ⋯ Postoperatively, our patient's non-verbal memory recovered to normal, but his verbal memory declined. Nevertheless, he was non-amnesic and seizure-free.
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Review
Cognitive side-effects of chronic antiepileptic drug treatment: a review of 25 years of research.
Over 90 investigations have been conducted over the past 25 years to determine what effect AEDs have on cognition. No satisfactory answer to this problem can be given, however, chiefly because there is a paucity of studies that pass fairly basic standards of methodology, design and analysis that apply to the evaluation of any clinical research. This severely limits the precision of statements regarding cognitive AED effects. ⋯ The choice of a study design based on a large treatment effect size may not always be appropriate, though. Of course, one could argue that it is only large effects that may be of practical or clinical significance anyways [30] and that effects of lesser magnitude are of no consequence. However, there are many examples where even a small benefit of one treatme
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Respiratory drive during status epilepticus and its treatment: comparison of diazepam and lorazepam.
In order to examine the respiratory effects of tonic-clonic seizures and their treatment with i.v. diazepam or lorazepam, we utilized a spontaneously breathing piglet seizure model. A tracheostomy, arterial catheter, and epidural electrodes were inserted and pigs were maintained under ketamine anesthesia. After baseline recordings, seizures were induced with a pentylenetetrazol (PTZ) bolus and a 20 min infusion (5-6 mg/kg/min). ⋯ Following anticonvulsants, the cumulative duration of seizures was significantly reduced in L and D groups, compared to C (P < 0.05). We conclude that increases in respiratory drive occur during tonic-clonic seizures induced with PTZ. Amelioration of seizure activity with lorazepam or diazepam results in a reduction in respiratory drive, but not respiratory failure, in this tracheostomized model.