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Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complex partial seizures comprise the major uncontrolled seizure type in adult patients with epilepsy. Any improvement of our understanding of the mechanisms through which these seizures are often refractory to antiepileptic drugs is therefore of considerable importance. By examining the effects of the anti-epileptic drug phenytoin in a large group of kindled rats, a widely used model of complex partial seizures, animals with different sensitivity to this drug were selected. Using determination of the focal seizure threshold for evaluation of phenytoin's anticonvulsant effect, most animals (about 60%) showed variable effects in response to phenytoin. However, about 20% of the animals ("phenytoin nonresponders") showed no increase in their focal seizure threshold at repeated test trials with phenytoin, and 20% ("phenytoin responders") exhibited reproducible increases in focal seizure threshold after injection of phenytoin. Phenytoin responders and nonresponders thus selected were used for subsequent experiments. The different response of focal seizures to phenytoin was not related to differences in pharmacokinetics or location of the stimulating electrode. Although phenytoin reproducibly increased the threshold for induction of afterdischarges in responders, it did not alter severity or duration of the elicited seizure response. In contrast to phenytoin, carbamazepine induced increases in focal seizure threshold in all kindled rats. Duration of seizures and afterdischarges were significantly reduced by carbamazepine in phenytoin responders, but not in nonresponders, although plasma levels of carbamazepine were the same in both groups. The difference in response of kindled rats to phenytoin was restricted to kindled seizures, because phenytoin induced the same anticonvulsant effect on the threshold for generalized tonic electroconvulsions (determined via transauricular electrodes) in both groups of kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kindling as a model of drug-resistant partial epilepsy: selection of phenytoin-resistant and nonresistant rats. 165 Aug 29

Eating epilepsy is a rare type of reflex epilepsy. A 24 years-old male with eating reflex complex partial seizures was submitted to clinical, neurological, neuroradiological and EEG studies. Neurologic and CT examinations were normal. EEG recordings including video-EEG monitoring during meals disclosed focal abnormalities related to both temporal lobes prevailing at the left side and secondary bilateral synchrony mainly in more anterior regions. Ictal findings were similar to the interictal secondary bilateral synchrony except for its longer duration. PB, VPA and DPH monotherapies were ineffective. High dose CBZ monotherapy yielded good but incomplete seizure control. Since a big number of precipitants could be involved, no specific physiopathological basis could be established.
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PMID:Eating epilepsy. 180 34

Controversy has arisen about the effectiveness of phenytoin against kindled seizures. It has been suggested that the reports of ineffectiveness could be accounted for by phenytoin being given by an intraperitoneal (i.p.) route in those experiments so that adequate serum concentrations were not achieved. Another possibility for the different results was dissimilar stimulus protocols employed in the various studies. The present study examined these issues. Doses of i.p. phenytoin were studied for their actions against kindled responses elicited with short (1 s) and long (10 s) stimulus trains through hippocampal electrodes. Serial application of the stimuli determined time-action relationships. Dose-dependent effects were demonstrated for all time points examined. There was a consistently greater suppression of kindled motor seizures than limbic behavioral seizures or electrographic seizures. Phenytoin either totally blocked or did not affect the duration of afterdischarges. Actions of phenytoin against responses by short duration stimuli were greater than against long duration stimuli. Additional pharmacokinetic studies compared i.p. versus intravenous (i.v.) phenytoin. After i.p. phenytoin, serum levels peaked later than after i.v. delivery, but were maintained in the 'therapeutic' range longer. The present experiments provide additional support for the idea that kindled seizures are a useful model for complex partial seizures in humans. In addition, they show that major actions of phenytoin are to decrease seizure spread and to elevate afterdischarge thresholds and that the i.p. route is appropriate for assaying the effect of phenytoin against kindled seizures in rats.
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PMID:Intraperitoneal phenytoin suppresses kindled responses: effects on motor and electrographic seizures. 188 15

A study of bio-availability of three drug companies' brands of phenytoin preparations (50mg capsule/tablets) was undertaken on 30 children with tonic-clonic or complex partial seizures. Eight children were excluded because of non-compliance and three because of abnormally high serum levels. Phenytoin capsules (Parke Davis) and tablets (Boots) produced significantly higher serum-level profiles than phenytoin tablets (Evans). Seizure frequencies did not differ significantly with the three brands of phenytoin. Dissolution of the three preparations tested in vitro was different. As a result of this study the authors recommend that children remain on the same manufacturer's brand of phenytoin throughout their treatment.
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PMID:Bio-availability and dissolution of three phenytoin preparations for children. 381 9

Diphenylhydantoin (DFH) is known to yield cerebellar ataxia in chronically treated epileptic patient due to cerebellar atrophy with loss of Purkinje cells. Little attention has been paid in the literature to the acute DFH intoxication bearing cerebellar symptoms. We report a patient afflicted with complex partial seizures due to a left temporal cyst, who has been treated during the last two years with DFH 100 mg/day. Due to the refractory characteristics of his seizures he was put on DFH 400 mg daily, and developed a pancerebellar syndrome. After surgical removal of the cyst his seizures entirely faded away and his cerebellar signs improved. Nevertheless his neurological examination still showed trunkal and lower limbs ataxia. After one year of follow up his neurological picture did not change, while he was seizures free. TC and MRI did not show cerebellar atrophy.
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PMID:[Persistent cerebellar ataxia after toxic administration of diphenylhydantoin]. 761 55

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. At a therapeutic concentration, topiramate (10 microM) enhanced GABA-stimulated (10 microM) Cl- influx into cerebellar granule neurons but did not significantly increase Cl- influx alone. Phenytoin (10 microM) and acetazolamide (300 microM) did not enhance GABA-stimulated Cl- influx. In patch-clamp electrophysiological studies, topiramate also enhanced GABA-evoked whole cell Cl- currents in mouse cerebral cortical neurons in culture. 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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PMID:Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. 933 82

Phenytoin has been reported to exert variable anticonvulsant effects in the kindling model of complex partial seizures. Phenytoin is only water soluble at a pH of more than 10, and it has been suspected that poor absorption of the drug is responsible for its lack of effect in some experiments. Recently, fosphenytoin, a prodrug of phenytoin, has been developed by phosphorylating phenytoin which makes the drug water soluble at physiological pH while it is rapidly transformed to phenytoin after injection. This study examined the anticonvulsant profile and the absorption after intraperitoneal injection of fosphenytoin, compared to its parental drug phenytoin. The pharmacokinetic parameters of phenytoin and fosphenytoin were compared by determining plasma levels of phenytoin after i.p. injection of 50 mg/kg phenytoin or the equivalent dose of 84 mg/kg of fosphenytoin in non-kindled female Wistar rats. After both injections the maximal plasma concentration of phenytoin was about 30 microg/ml. The relative bioavailability of fosphenytoin was 83%. In contrast to phenytoin, failed injections resulting in non-detectable plasma concentration of phenytoin were almost absent after fosphenytoin. In fully kindled female Wistar rats, fosphenytoin dose-dependently increased the focal seizure (afterdischarge) threshold. Seizure severity and duration at threshold were reduced only after the highest does of fosphenytoin tested (84 mg/kg). Thus, fosphenytoin showed anticonvulsant properties similar to phenytoin in amygdala kindled rats. We conclude that fosphenytoin is an adequate and reliable substitute for the parenteral injection of phenytoin in experimental seizure models of rats.
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PMID:Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin. 955 46

We report the case of a 39-year-old woman with onset of daily epigastric sensations associated with brief episodes of unresponsive blank stare, which have been interpreted as complex partial seizures with occasional secondary generalisation. Phenytoin as monotherapy and in combination with valproate had not been effective. During video-EEG we recorded typical absences with brief 3 second spike, and slow-wave discharges of up to 5 seconds, which were recognized by the patient herself. All absences were preceded by epigastric sensations. There was no indication of focal epilepsy. Monotherapy with valproate substantially decreased the frequency of the absences. In conclusion, this case is peculiar for several reasons: 1) late onset of absence epilepsy, 2) epigastric sensation at onset of absence seizures, 3) recognition of brief "phantom" absences and 4) presumable adverse effects of phenytoin.
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PMID:Epigastric sensations as an unusual manifestation of adult absence epilepsy. 1131 17

Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.
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PMID:[Treatment of status epilepticus]. 1223 7

Kainate-induced seizures and seizures induced by tossing stimulation in epilepsy-prone EL mice are considered as models of complex partial seizures. We used these models to evaluate the anticonvulsive effects of 2-[ N-(4-chlorophenyl)- N-methylamino]-4 H-pyrido[3.2-e]-1,3-thiazin-4-one (YM928), a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. In the kainate-induced seizure test in rats, wet-dog shakes (WDS) were reduced by oral administration of YM928 at doses of 7.5 mg/kg and 30 mg/kg. YM928 (15 mg/kg) reduced the number of WDS within the first 80 min, but then prolonged the time of occurrence compared with the other groups. Significant reduction in kainate-induced motor seizure was observed with 4-30 mg/kg. YM928 did not induce apparently abnormal behaviour at doses of 2-15 mg/kg but did induce sedation at 30 mg/kg. Carbamazepine (40 or 80 mg/kg), valproate (600 mg/kg), diazepam (2.5 mg/kg), and phenobarbital (20 or 40 mg/kg) exerted anticonvulsant effects against motor seizures, but only valproate, at a dose that also caused sedation, suppressed WDS. Phenytoin and ethosuximide did not show significant anti-kainate effects. In the tossing stimulation test in EL mice, i.p. injection of YM928 at 5 mg/kg or 10 mg/kg significantly increased the number of stimulations required to elicit generalized seizure. Carbamazepine (4 or 8 mg/kg), phenytoin (8 or 16 mg/kg), valproate (100-400 mg/kg), diazepam (0.5 mg/kg), phenobarbital (1.3 or 2.5 mg/kg) and ethosuximide (75-300 mg/kg) exerted significant anticonvulsant effects against these seizures. These results indicate that YM928 has anticonvulsant effects on seizure models that are characteristic of partial onset seizures in humans. YM928 is expected to have beneficial effects against human complex partial seizure with secondary generalization or temporal lobe epilepsy.
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PMID:Effect of YM928, a novel AMPA receptor antagonist, on seizures in EL mice and kainate-induced seizures in rats. 1532 31


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