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

Visual disturbances are a common side-effect of many antiepileptic drugs. Non-specific retino- and neurotoxic visual abnormalities, that are often reported with over-dosage and prolonged AED use, include diplopia, blurred vision and nystagmus. Some anticonvulsants are associated with specific visual problems that may be related to the mechanistic properties of the drug, and occur even when the drugs are administered within the recommended daily dose. Vigabatrin, a GABA-transaminase inhibitor, has been associated with bilateral concentric visual field loss, electrophysiological changes, central visual function deficits including reduced contrast sensitivity and abnormal colour perception, and morphological alterations of the fundus and retina. Topiramate, a drug that enhances GABAergic transmission, has been associated with cases of acute closed angle glaucoma, while tiagabine, a GABA uptake inhibitor, has been investigated for a potential GABAergic effect on the visual field. Only mild neurotoxic effects have been identified for patients treated with gabapentin, a drug designed as a cyclic analogue of GABA but exhibiting an unknown mechanism while carbamazepine, an inhibitor of voltage-dependent sodium channels, has been linked with abnormal colour perception and reduced contrast sensitivity. The following review outlines the visual disturbances associated with some of the most commonly prescribed anticonvulsants. For each drug, the ocular site of potential damage and the likely mechanism responsible for the adverse visual effects is described.
Seizure 2004 Mar
PMID:The effect of antiepileptic drugs on visual performance. 1512 41

Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment. One of the implicated mechanisms is enhancement of apoptotic neuronal death, which occurs physiologically in the developing brain. We investigated whether topiramate, one of the newer antiepileptic drugs, has neurotoxic properties in the developing rat brain. Topiramate slightly but significantly enhanced apoptotic neuronal death in the 7-day-old rat brain at doses of 50 mg/kg and above. These doses are several folds higher than reported ED(50) doses in infant rodent seizure models that respond to topiramate. Electron microscopy confirmed that dying neurons following topiramate treatment displayed the same morphological features as neurons undergoing physiological cell death during development. When compared to the neurotoxicity profile of phenytoin, valproate, and phenobarbital, the separation between the effective anticonvulsant dose and the neurotoxic dose was greater for topiramate and the neurotoxic effect was lower.
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PMID:Therapeutic doses of topiramate are not toxic to the developing rat brain. 1514 66

For the treatment of patients with chronic refractory epilepsies, information about the long-term efficacy and safety profile of any new antiepileptic drug is crucial. Topiramate has been proven to be effective in patients with refractory chronic partial epilepsies in short-term controlled clinical trials, but the long-term retention, long-term efficacy, and long-term side-effect profile have not been sufficiently investigated. We analyzed all patients who had been treated with topiramate in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in the spring of 1993 up to a final assessment point in mid-2002. In total, 470 patients were identified. The data show that the clinical dose achieved was about 200mg/day, reached after approximately 6 months of treatment. Further dose escalation in the survivors was slow, with a mean dose of about 300 mg/day after 24 months of treatment. Mean titration dose is 25mg/week, but titration strategy is mostly individual and responds to patient complaints. With respect to seizure frequency, 10-15% of the patients were seizure-free at the 6-month evaluation; 4 patients achieved a 2-year remission. Retention rate was 53% after 1 year, 45% after 2 years, 38% after 3 years, and 30% after 4 years. At 4 years, almost 70% of the patients had discontinued topiramate. The main reason was adverse events, which accounted for about 65% of the discontinuations. Behavioral side effects were dominant, with mental slowing (27.6%), dysphasia (16.0%), and mood problems (agitation: 11.9%) being the most frequently reported side effects. In about 10% of the patients side effects led to discontinuation despite the obvious favorable effects on seizure frequency. Comparisons between the patients who discontinued topiramate treatment and those who continued topiramate showed that discontinuation was associated with comedication (vigabatrin and lamotrigine). Our conclusion is that TPM is associated with a high incidence of side effects in clinical practice, affecting long-term retention. Meaningful prognostic factors that may help us in clinical decision making, i.e., to prevent the side effects or to help us identify those at risk, have not been found.
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PMID:Topiramate in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center. 1514 8

The efficacy of topiramate, a novel therapeutic agent approved for the treatment of seizure disorders, was evaluated in a model of traumatic brain injury (TBI). Adult male rats were anesthetized (sodium pentobarbital, 60 mg/kg, i.p.), subjected to lateral fluid percussion brain injury (n = 60) or sham injury (n = 47) and randomized to receive either topiramate or vehicle at 30 min (30 mg/kg, i.p.), and 8, 20 and 32 h postinjury (30 mg/kg, p.o.). In Study A, memory was evaluated using a Morris water maze at 48 h postinjury, after which brain tissue was evaluated for regional cerebral edema. In Study B, animals were evaluated for motor function at 48 h and 1, 2, 3, and 4 weeks postinjury using a composite neuroscore and the rotating pole test and for learning ability at 4 weeks. Brains were analyzed for hemispheric tissue loss and hippocampal CA3 cell loss. Topiramate had no effect on posttraumatic cerebral edema or histologic damage when compared to vehicle. At 48 h, topiramate treatment improved memory function in sham but not brain-injured animals, while at one month postinjury it impaired learning performance in brain-injured but not sham animals. Topiramate significantly improved composite neuroscores at 4 weeks postinjury and rotating pole performance at 1 and 4 weeks postinjury, suggesting a potentially beneficial effect on motor function following TBI.
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PMID:Differential effects of the anticonvulsant topiramate on neurobehavioral and histological outcomes following traumatic brain injury in rats. 1516 59

The primary goals of antiepileptic treatment are complete cessation of seizure without any adverse reaction. In adult refractory focal epilepsies, a rational approach is based on adequate syndromic categorization and accurate knowledge of the pharmacological properties of antiepileptic drugs, whose number has significantly increased in recent years. Since 1991 nine new antiepileptic medications have been marketed in France, i. e. by order of appearance, vigabatrin (Sabril), felbamate (Taloxa), gabapentin (Neurontin), lamotrigine (Lamictal), tiagabine (Gabitril), fosphenytoin (a water-soluble phenytoin prodrug, Prodilantin), topiramate (Epitomax), oxcarbazepine (Trileptal) and levetiracetam (Keppra). Efficacy of these new compounds in focal epilepsies is proven, and in some patients with middle-severity focal epilepsy, clinical benefit is significant. Improvement is especially significant in terms of tolerability, ease of use and reduced interaction potential. However, some of these drugs (tiagabine, topiramate) may have an unfavorable short-term tolerance profile, while others (felbamate, lamotrigine) expose patients to a potential risk of severe acute idiosyncratic reactions. Increased availability of new drugs and the fact that drug monitoring has been claimed to be of little or no value in newly-marketed drugs have paradoxically strongly complicated therapeutic options. Moreover, only a few patients with truly refractory focal epilepsy can be made seizure-free by these new compounds, and the search for more effective anticonvulsants should continue in addition with alternative therapies or surgery.
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PMID:[Treatment protocol for long-term anti-epilepsy drugs in adults with refractory partial epilepsy]. 1533 73

We performed a prospective study to evaluate the effect of topiramate as an adjunctive therapy in Taiwanese children with intractable partial epilepsy and generalized epilepsy. Thirty children aged from 2 to 16 years (8.5 +/- 3.8 years) were enrolled in this study. Eighteen children (60.0%) had partial epilepsy, and 12 children (40.0%) had generalized epilepsy. These children were experiencing more than one seizure per month even under a stable antiepileptic regimen treatment. Topiramate was begun at 1 mg/kg x day, and the dosage was raised by 1 mg/kg x day each week. Titration continued for 4 weeks or more. The maximal dosage was 10 mg/kg x day. In children with partial epilepsy, six children (33.3%) achieved > or = 50% frequency reduction, while eight children (44.4%) achieved a seizure-free state. In children with generalized epilepsy, including infantile spasms, four children (33.3%) achieved > or = 50% frequency reduction, while five children (41.7%) achieved a seizure-free state. The most common adverse effect was poor appetite (10.0%). No idiosyncratic reactions to topiramate were found. Only one patient discontinued topiramate because of central hyperventilation. Topiramate can be used as an adjunctive antiepileptic drug for intractable epileptic children in Taiwan.
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PMID:Effect of topiramate on intractable seizures in Taiwanese children. 1547 76

Topiramate is an effective treatment for several types of seizures. The aim of this study is to assess the efficacy and tolerability of slow topiramate dose titration as add-on therapy in childhood epilepsy. This investigation is a prospective open-label, single-center, add-on study in 22 children with a diagnosis of refractory epilepsy. Topiramate (dose 0.5-2 mg/kg/day) was titrated at 2-week intervals up to the recommended dose of 6-12 mg/kg/day. Seizure frequency rate reduction was significant, declining from 23 +/- 5.1 seizures/week (mean +/- S.E.M.) at baseline phase to 3.5 +/- 1.2 seizures/week at the end of the 16-week stabilization phase (P < 0.001). After 16 weeks of stabilization, 19 patients (86%) had more than 50% seizure reduction. Seven patients (31%) were 100% seizure-free. Two patients (9%) manifested no improvement; only one patient (5%) did not tolerate the added drug and discontinued topiramate. One patient manifested severe side effects, whereas 21 patients experienced mild to moderate side effects mostly represented by somnolence, nervousness, and anorexia with or without weight loss. We conclude that slow dose titration improves efficacy and tolerability of topiramate as add-on therapy in the treatment in refractory epilepsy.
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PMID:Topiramate slow dose titration: improved efficacy and tolerability. 1551 17

Topiramate, a new anticonvulsant, has been reported to possess neuroprotective effects in both in vivo and in vitro experiments. In the present study, the effect of topiramate (40 and 80 mg/kg ip) on the fully developed kainate-induced status epilepticus was evaluated in the rat. Injection of kainate (15 mg/kg ip) evoked recurrent limbic seizures which lasted several hours. Topiramate injected 1.5 h after kainate administration had no effect on the seizures and mortality of the animals. Biochemical study revealed that at 80 mg/kg ip, topiramate significantly attenuated the kainate-induced lipid peroxidation in the piriform cortex and showed similar tendency in the frontal cortex. Besides the central nervous system, the kainate-induced seizures evoked significant changes in immunoreactivity, such as reduction in thymus weight and the proliferative activity of splenocytes, and the splenocyte-increased production of interleukin-10, but not interferon-gamma. Topiramate did not affect the kainate-induced reduction in thymus weight, but attenuated changes in the proliferative activity of splenocytes. It is concluded that topiramate, when given during the fully developed kainate-induced status epilepticus in rats, has no effect on seizures, but attenuates lipid peroxidation in piriform cortex and prevents certain changes in immunoactivity.
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PMID:Effect of topiramate on the kainate-induced status epilepticus, lipid peroxidation and immunoreactivity of rats. 1559 43

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.
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PMID:Effect of topiramate on seizures and respiratory dysrhythmia in Rett syndrome. 1560 67

An open-label retrospective study was conducted to assess the effectiveness and tolerability of topiramate in children and adolescents with pervasive developmental disorders (PDD). Topiramate is a novel antiepileptic drug approved as an adjunctive treatment for seizure disorders. A retrospective chart review was conducted in an outpatient clinic specialized in treating individuals with developmental disabilities, to identify all children and adolescents with PDD who received topiramate. Patients were included if concomitant medications remained unchanged. Treatment response was assessed using the Global Improvement item of the Clinical Global Impressions scale (CGI-GI), based on a review of medical records and the Conners Parent Scale (CPS), as completed by parents. Fifteen patients were identified (12 male, 3 female; age = 14.7 +/- 3.3 years), including 11 patients with autistic disorder, 2 patients with Asperger's disorder, and 2 patients with PDD not otherwise specified (PDD, NOS). Eight patients (4 patients with autistic disorder, 2 patients with Asperger's disorder, and 2 patients with PDD, NOS) were judged to be responders, as defined by a score of 1 or 2 on the CGI-GI. Treatment duration was 25 +/- 16 weeks, and the mean dose was 235 +/- 88 mg. Differences between baseline and the end-of-trial period were observed in the following CPS subscales: conduct, hyperactivity, and inattention. No differences were noted in the psychosomatic, learning, and anxiety subscales. Three patients discontinued topiramate because of side effects, with 2 patients experiencing cognitive difficulties and 1 patient a skin rash. Topiramate may be beneficial for treating secondary symptoms of PDD, and prospective openlabel studies and double-blind, placebo-controlled studies to assess its efficacy and safety are needed.
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PMID:A retrospective assessment of topiramate in children and adolescents with pervasive developmental disorders. 1565 Apr 99


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