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

Topiramate had well-documented efficacy as an adjunctive agent for partial-onset seizures in 5 double-blind, parallel trials, reducing seizure frequency by 35-47% at 400 mg/day, the optimal dose for most patients. It can also be used as monotherapy for partial-onset seizures. A broad spectrum of action is suggested by studies showing efficacy against a variety of generalized-onset seizure types, including primary generalized tonic-clonic seizures and the component seizures of Lennox-Gastaut syndrome. The major adverse effects of topiramate are of CNS origin. Psychomotor slowing is most common, but disappears in most patients with time or dosage adjustments; 11-28% of patients discontinue the drug because of side effects. No serious skin, liver or blood toxicity has been identified. Efficacy and adverse effect profiles are similar for children and adults. Introduction at rates not exceeding 25-50 mg increases per week will minimize adverse effects and be satisfactory for most adults.
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PMID:Clinical studies of topiramate. 1297 9

Topiramate is an antiepileptic drug that has a broad spectrum of antiseizure effects, which appear to be the result of several neurostabilising pharmacological mechanisms. These include blockade of ion channels, potentiation of GABA neuroinhibition and glutamate receptor antagonism at non-NMDA receptors, as well as mild inhibition of carbonic anhydrase. Topiramate monotherapy dose dependently reduced the number of patients who met seizure related exit criteria in children (aged > or =6 years) and adults with epilepsy. This effect was also observed in patients who had previously experienced partial onset seizures and for those who had experienced generalised tonic clonic seizures. Six-month and 1-year seizure-free rates were dose-dependently reduced. In epilepsy, topiramate monotherapy 100 or 200 mg/day was as effective as carbamazepine 600 mg/day or valproate 1250 mg/day as measured by time to study exit for any reason, time to first seizure and percentage of patients seizure-free in the final 6 months of treatment (mean treatment duration 244 days). Adverse events associated with topiramate monotherapy that were dosage related included paraesthesia, weight loss and diarrhoea. Renal calculi were also reported in both fully published trials.
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PMID:Topiramate: as monotherapy in newly diagnosed epilepsy. 1453 52

The lithium-pilocarpine model reproduces the main characteristics of human temporal lobe epilepsy. After status epilepticus (SE), rats exhibit a latent seizure-free phase characterized by development of extensive damage in limbic areas and occurrence of spontaneous recurrent seizures. Neuroprotective and antiepileptogenic effects of topiramate were investigated in this model. SE was induced in adult male rats by LiCl (3 mEq/kg) followed 20 h later by pilocarpine (25 mg/kg). Topiramate (10, 30, or 60 mg/kg) was injected at 1 and 10 h of SE. Injections were repeated twice a day for six additional days. Another group received two injections of diazepam on the day of SE and of vehicle for 6 days. Neuronal damage was assessed at 14 days after SE by cell counting on thionin-stained sections. Occurrence of spontaneous recurrent seizures (SRS) was videorecorded for 10 h per day in other groups of rats. In diazepam-treated rats, the number of neurons was dramatically reduced after SE in all subregions of hippocampus and layers II-IV of ventral cortices. At all doses, topiramate induced a 24 to 30% neuroprotection in layer CA1 of hippocampus (p < 0.05). In CA3b, the 30-mg/kg dose prevented neuronal death. All rats subjected to SE became epileptic. The latency (14-17 days) to and frequency of SRS were similar in topiramate- and diazepam-treated rats. The high mortality in the 30 mg/kg topiramate group (84%) was possibly the result of interaction between lithium and topiramate. In conclusion, topiramate displayed neuroprotective properties only in CA1 and CA3 that were not sufficient to prevent epileptogenesis.
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PMID:Neuroprotective properties of topiramate in the lithium-pilocarpine model of epilepsy. 1459 82

An Internet questionnaire was used to collect data from caregivers about seizure activities and drug therapies of patients with Angelman's syndrome (AS). A questionnaire to collect data on AS patient demographics, seizure types, laboratory diagnosis, and past history of anticonvulsant use was developed and distributed among the membership of multiple AS groups primarily through the Internet. Caregivers of AS patients were asked to rate each drug listed on the questionnaire for its effect on the patient's behavior and alertness and on the severity and frequency of the patient's seizures. A 6-point rating scale was used, with the lowest score representing the most favorable effect. Primary considerations of the survey were to reach as many people as possible, anonymously and quickly, in a widely comprehensible format. Data were collected between March 22 and October 9, 2002. Of the 88 complete questionnaires received, 75 were electronic and 13 were handwritten responses. Forty-seven percent of respondents reported patients' use of a combination of medications at some point, with 59 different combinations described, 21 of which consisted of three or more medications. The most commonly reported regimens were valproic acid and clonazepam, valproic acid and topiramate (with or without clonazepam), valproic acid and lamotrigine, and phenytoin and carbamazepine. Patient characteristics and seizure types were consistent with those of AS patients described in the literature. Topiramate and ethosuximide were rated favorably, consistent with previously published reports. Responses to the questionnaire were widespread and rapid, with 42 responses collected in the first week. An Internet questionnaire helped collect self-reported efficacy information from caregivers of AS patients.
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PMID:Assessment of anticonvulsant effectiveness and safety in patients with Angelman's syndrome using an Internet questionnaire. 1473 75

Topiramate (TPM), a new generation antiepileptic drug was investigated for its anticonvulsant effects in various models of genetically determined and chemically induced epilepsy in rodents. In addition, based on recent electrophysiological data suggesting that TPM may interact with L-type Ca(2+) channels, we evaluated the effects of a concomitant administration of L-type Ca(2+) channel modulators on TPM's antiepileptic properties. TPM, dose-dependently, protected against audiogenic seizures in DBA/2 mice. Concomitant treatment with TPM and a low dose of L-type Ca(2+) channel antagonists nifedipine or verapamil or with the L-type Ca(2+) channel agonist, S(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (Bay k 8644) was able to increase the ED(50) for this drug. TPM also protected against seizures induced by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), 4-aminopyridine (4-AP) and pentylenetetrazole (PTZ), but this activity was not significantly modified by nifedipine. TPM, dose-dependently, reduced the number and duration of epileptic spike-wave discharges (SWDs) both in WAG/Rij rats and lethargic (lh/lh) mice, two genetic models of absence epilepsy. Nifedipine decreased TPM's activity in WAG/Rij rats but paradoxically enhanced it in lh/lh mice, whereas Bay k 8644 displayed opposite effects in both absence models. These results confirm TPM's broad spectrum of anticonvulsant activity and support the proposal that a modulation of neuronal L-type Ca(2+) channel activity plays an important role in its antiepileptic activity.
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PMID:Nifedipine affects the anticonvulsant activity of topiramate in various animal models of epilepsy. 1503 46

In a novel double-blind trial, topiramate was compared with the investigator's choice of carbamazepine or valproate as first-line therapy in patients as young as 6 years of age with newly diagnosed epilepsy. Among 613 patients enrolled in the trial, 119 (19%) were children or adolescents (6-16 years of age). No differences between fixed doses of topiramate (100 and 200 mg/day) and carbamazepine (600 mg/day) or valproate (1250 mg/day) were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients who were seizure free during the last 6 months of treatment. Topiramate 100 mg/day (2.0 mg/kg/day in this study population) was associated with the fewest discontinuations owing to side effects. Based on efficacy and tolerability, the recommended target dose for topiramate as first-line therapy in children and adolescents is 100 mg/day.
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PMID:Topiramate, carbamazepine, and valproate monotherapy: double-blind comparison in children with newly diagnosed epilepsy. 1507 7

Canavan disease (CD) is a rare autosomal recessive genetic disorder characterized by early onset progressive spongy degeneration of the brain involving the axon's myelin sheath. Patients with CD have leukoencephalopathy and megalencephaly; clinically they show a variable course ranging from slow neurodegenerative course to no neurological development or rapid regression. Current treatment is symptomatic including management of seizures and spasticity. Topiramate (TPM) is a novel antiepileptic drug for treatment of a broad spectrum of seizure types in adults and children. We used TPM in two of our patients diagnosed with CD at six months of age. At seven months and 15 months' follow-up, respectively, each patient showed a decrease in head growth velocity. We suggest that TPM can be used in patients with CD and possibly in other childhood neurodegenerative diseases with leukoencephalopathy and megalencephaly. Further studies are required to reveal the underlying mechanisms that lead to decreased head growth velocity, and to conclude whether this ameliorates the clinical course of CD.
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PMID:Effect of topiramate on enlargement of head in Canavan disease: a new option for treatment of megalencephaly. 1507 77

Topiramate, a novel anticonvulsant drug, has CNS depressant activity including enhancement of GABAergic inhibitory synaptic transmission. Drugs of this pharmacological spectrum might have utility in assuaging drug addiction. This study analyzes the ability of TPM to reduce withdrawal signs in the kindling model of ethanol dependence: chronic intermittent ethanol (CIE) rats. After CIE, persistent withdrawal signs are shown by an increased seizure susceptibility to the convulsant drug pentylenetetrazol and increased anxiety measured on the elevated plus-maze. Topiramate increased significantly the PTZ seizure threshold in CIE but not in control rats. On the elevated plus-maze, Topiramate was markedly more effective in CIE rats than in controls. Topiramate may have a therapeutic efficacy in treating alcohol withdrawal symptoms.
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PMID:Topiramate attenuates withdrawal signs after chronic intermittent ethanol in rats. 1510 59

Although the mechanism of action of topiramate is not fully understood, its anticonvulsant properties may result, at least in part, from an interaction with AMPA/kainate receptors. We have recently shown that topiramate selectively inhibits postsynaptic responses mediated by GluR5 kainate receptors. To determine if this action of topiramate is relevant to the anticonvulsant effects of the drug in vivo, we determined the protective activity of topiramate against seizures induced by intravenous infusion of various ionotropic glutamate receptor agonists in mice. Topiramate (25-100 mg/kg, i.p.) produced a dose-dependent elevation in the threshold for clonic seizures induced by infusion of ATPA, a selective agonist of GluR5 kainate receptors. Topiramate was less effective in protecting against clonic seizures induced by kainate, a mixed agonist of AMPA and kainate receptors. Topiramate did not affect clonic seizures induced by AMPA or NMDA. In contrast, the thresholds for tonic seizures induced by higher doses of these various glutamate receptor agonists were all elevated by topiramate. Unlike topiramate, carbamazepine elevated the threshold for AMPA- but not ATPA-induced clonic seizures. Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors. Protection from tonic seizures may be mediated by other actions of the drug. Together with our in vitro cellular electrophysiological results, the present observations strongly support a unique mechanism of action of topiramate, which involves GluR5 kainate receptors.
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PMID:Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. 1511 Oct 16

Many studies showed that Topiramate (TPM) may be a useful drug in a wide spectrum of childhood epilepsies. We report a 3-month-old female with stormy onset of secondarily generalized partial seizures. She showed a high seizure frequency and a progressive worsening electroencephalogram (EEG), despite standard antiepileptic drugs administration. TPM succeeded in controlling seizures, even after the other drugs were discontinued. This case suggests that TPM may represent a good choice for the treatment of partial seizures refractory to conventional drugs in infants.
Seizure 2004 Jun
PMID:Topiramate efficacy in an infant with partial seizures refractory to conventional antiepileptic drugs. 1512 Nov 32


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