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Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.
Epilepsy Res 1995 May
PMID:Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial. 764 74

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.
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PMID:Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. 769 32

The validity of a patient-based scale, presumably measuring adverse effects of drugs on cognitive function, was examined in a normal volunteer study. Thirty subjects were randomly assigned to placebo or one of two doses of a benzodiazepine, temazepam (10 mg and 20 mg), in a double-blind placebo-controlled parallel group design. Plasma samples were taken before the scale was completed and up to 8 hours post-dose. After administration of the medication the subjects were asked to maintain their normal daily routine as much as possible (reading, studying, conversations). The inventory was administered twice, at 50 minutes and 2 hours post-dose (peak level). The overall score was different between the three groups, only for the second assessment, 2 h post-dose (ANOVA, P < 0.02). Multiple t-testing between the three groups revealed statistically significant differences between placebo and the 10 mg temazepam group (P = 0.02) and between placebo and the 20 mg temazepam group (P = 0.006). No significant difference was found between the two temazepam groups. Analysis of the separate questions showed least sensitivity for questions related to the domain of 'hyperexcitability' and most sensitivity for 'fatigue' and 'slowing.' The overall score appeared to be sensitive already for the lower toxicity range suggesting an 'all or nothing effect'. The subjective reports, collected by using this scale, may therefore be used for the detection of gross overall changes in cognitive functioning.
Epilepsy Res 1995 Mar
PMID:The Neurotoxicity Scale: the validity of a patient-based scale, assessing neurotoxicity. 779 95

The aims of treating epilepsy are to stop seizures, and to neutralize any associated cognitive or psychosocial penalty associated with epilepsy or its treatment. Inappropriate medication and/or continuance of seizures have deleterious effects on quality of life. The Epilepsy Task Force devised a 30-item questionnaire which was sent to children with epilepsy whose families are members of the British Epilepsy Association. The 896 replies which were received within the first two weeks have been analysed. Forty-two per cent of respondents had tonic-clonic seizures. Thirty-five per cent had had no seizures within the previous six months, but 29% reported seizures which occurred at least once a week. Although 42% didn't mind their seizures, the remaining respondents described their seizures as making them feel helpless, scared, panicky, frustrated and different from others. The most common medications were carbamazepine and sodium valproate. Side effects attributed to the medication included tiredness, difficulty in concentrating, dizziness, headache, irritability and weight gain. Thirty-six per cent said that their doctor had never explained about their epilepsy. The questionnaire included space for free-text comments and these were made by more than 400 respondents.
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PMID:Quality of life--a view from the playground. 789 45

Fifteen women with pharmacologically intractable epilepsy were given physical exercise (aerobic dancing with strength training and stretching) for 60 min, twice weekly, for 15 weeks. Seizure frequency was recorded by the patients for 3-7 months before the intervention, during the intervention period, and for 3 months after the intervention. Medication and other known seizure-influencing factors were kept as constant as possible. Self-reported seizure frequency was significantly reduced during the intervention period. The exercise also led to reduced level of subjective health complaints, such as muscle pains, sleep problems, and fatigue. The exercise reduced plasma cholesterol ratio and increased maximum O2 uptake. Because most of the patients were unable to continue the exercise on their own after the intervention period, the exercise effects were not maintained during the follow-up period. The patients were not unwilling to continue the exercise, but it was not sufficient to offer them the possibility of continuing similar types of exercise. We believe that 15 weeks is too short a time to establish a life-style change and that continued physical exercise for these patients requires a well-organized and supportive program, requiring experienced and dedicated instructors.
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PMID:Physical exercise in women with intractable epilepsy. 798 19

The new antiepileptic drug vigabatrin acts by preventing degradation of the inhibitory neurotransmitter GABA (gammaaminobutyric acid). This appears to decrease propagation of abnormal hypersynchronous discharges, thus reducing seizure activity. In an open study in 46 patients with intractable epilepsy, supplementary therapy with vigabatrin reduced seizure by at least 50% in 15 patients. Three patients became seizure-free. The best effect of vigabatrin is seen in patients with partial epilepsy. Tiredness and irritability were the most frequently reported side effects, but these were usually mild and transient.
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PMID:[Vigabatrin--a new antiepileptic agent]. 799 31

Health-related quality of life (HRQOL) of 166 adults who had previously undergone surgical treatment for intractable epilepsy was compared with that of outpatients with hypertension, diabetes, heart disease, and/or depressive symptoms. Eight self-reported HRQOL domains were evaluated and compared by the RAND 36-Item Health Survey 1.0: emotional well-being, social function, role limitations due to emotional problems, energy/fatigue, pain, role limitations due to physical problems, physical function, and general health perceptions. A pictorial item on overall QOL was also administered, for a total of 9 HRQOL domains. With adjustment made for age, gender, education, and comorbid conditions, 55 completely seizure-free patients scored higher (i.e., better health) than patients with hypertension in 6 of 9 domains, higher than diabetic patients in 8 of 9, higher than those with heart disease in all 9, and higher than those with depressive symptoms in all 9 (all p < 0.05). Sixty-seven patients still having seizures with impaired consciousness scored worse than hypertensive patients in 5 domains, worse than diabetic patients in 3, and worse than heart disease patients in 2; for all 3 conditions, these domains included emotional well-being and overall QOL (p < 0.05). These 67 patients, however, scored better than patients with depressive symptoms in all 9 domains, better than those with heart disease in 2, and better than those with diabetes in 1 (all p < 0.05). Forty-four other patients had only simple partial seizures (SPS); their scores were comparable to those of diabetic and heart disease patients on mental and social health scales but were higher ("better") than those of these patients on physical health scales. HRQOL among patients who have undergone "curative" epilepsy surgery is better than that of patients who have hypertension, diabetes, heart disease, or depressive symptoms. Patients who have continued seizures with altered consciousness are worse off in terms of emotional well-being and overall QOL than all other patients, except for those with depressive symptoms.
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PMID:Quality of life of epilepsy surgery patients as compared with outpatients with hypertension, diabetes, heart disease, and/or depressive symptoms. 802 6

Vigabatrin was designed to increase the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. It does this by replacing GABA as a substrate for the action of the catabolic enzyme GABA-transaminase. As a result of this inhibition, neuronal GABA levels are elevated, resulting in enhanced endogenous GABA transmission. A number of clinical trials assessing the effect of vigabatrin in epilepsy have been completed. Vigabatrin is of proven benefit in partial seizures and secondarily generalised tonic clonic seizures, and it is licensed for use as adjunctive therapy in these conditions in several European countries. It has been shown to be effective in some epilepsy syndromes in children including West's syndrome, infantile spasms and cryptogenic partial seizures. Its effect on primary generalised tonic clonic seizures is variable, while there is considerable evidence that it has a deleterious effect on myoclonic and absence seizures. There have been a few reports of the benefits of vigabatrin in other neurological disorders including tardive dyskinesia, degenerative ataxias and GABA metabolism disorders. The adverse effects associated with vigabatrin are similar to those seen with other anticonvulsants, with a predominance of CNS effects including somnolence, fatigue, irritability, dizziness and headache. Psychiatric symptoms including depression and psychosis are seen in a small number of patients and cause the most problems. These often necessitate discontinuation of vigabatrin, which usually results in resolution of symptoms.
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PMID:A risk-benefit assessment of vigabatrin in the treatment of neurological disorders. 803 89

Fifteen patients who experienced epileptic seizures while playing video games are described together with a review of 20 cases in the English literature. Nine of the 15 cases and all but two of the reported cases experienced their first seizure while playing video games. Two thirds of patients had idiopathic generalised epilepsy and mainly reported generalised tonic clonic seizures, but some had typical absence seizures and myoclonic jerks while playing video games. In this series, 30% with idiopathic generalised epilepsy had juvenile myoclonic epilepsy. Overall, 70% of patients with idiopathic generalised epilepsy were photosensitive to intermittent photic stimulation and the mechanism of seizure provocation was probably similar to that of television induced seizures, although sensitivity to specific patterns was sometimes important. Two children had self induced video game seizures. Non-photic factors such as excitement, fatigue, sleep deprivation, cognitive processing, and diurnal variation in susceptibility seemed to be important seizure precipitants, particularly in non-photo-sensitive patients. Twenty nine per cent of patients had partial (mainly occipital) video game associated seizures. Occipital spikes were common in the EEG of these patients. Photosensitivity to intermittent photic stimulation may have been important in two patients but in the others, who all played arcade video games, other mechanisms need to be considered. Video game associated seizures are a feature of several epileptic syndromes and differ in precipitants and appropriate management.
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PMID:Video game induced seizures. 805 15

We made a long term prospective study of 66 patients with juvenile myoclonic epilepsy (JME). Prevalence was 10.2% among 672 patients with epilepsies. Sex distribution was equal. Sixty-three were not diagnosed on referral; JME was not initially recognized in the epilepsy clinic in 22. Clinical typical absence seizures were reported in 33.3%, myoclonic jerks in 97% and generalized tonic-clonic seizures (GTC) in 78.8% of the patients. Mean age (+/- SD) at onset was 10.5 +/- 3.4 years (range 5-16 years) for absence seizures, 15 +/- 3.5 years (range 8-26 years) for myoclonic jerks, and 16 +/- 3.5 years (9-28) years (range 1-9 years) and GTC by 4.4 +/- 2.7 years (range 1-8 years) in 14 (21.2%) patients who manifested all three types of seizure. Absence were never antedated by myoclonic jerks or GTC. Myoclonic jerks occurred on awakening in 87.5% of the patients. GTC occurred mainly on awakening, but other patients had nocturnal or diurnal GTC with no circadian distribution. Neurologic examination was normal for all patients except for tremor of the hands similar to essential tremor, noted in 35% of patients. Computed tomography (CT) brain scans were normal: 93% of patients had precipitating factors: sleep deprivation (89.5%), fatigue (73.7%), photosensitivity (36.8%; television and video games 8.8%), menstruation (24.1% of women), mental concentration (22.8%), and stress (12.3%). Incidence of JME among siblings (13 of 41 examined families) implies an autosomal recessive mode of inheritance for this Arab population. EEGs were frequently normal in treated patients. At least one abnormal EEG was recorded in 56 (84.9%) patients. Abnormalities consisted mainly of generalized discharges of spike/double spike and/or polyspike and slow wave. Frequent multiple spikes and discharge fragmentations varied from 0.5- to 20-s duration (mean 6.8 s). Twenty (30.3%) had focal abnormalities, and 18 (27.3%) had photoconvulsive discharges. Eighty-eight percent of patients remained seizure-free for > or = 3 years of follow-up. Effective treatment was achieved with valproate (VPA); control of myoclonic jerks was improved with clonazepam (CZP). CZP monotherapy did not consistently prevent GTC. Adding small doses of CZP with simultaneous reduction of VPA was the most effective and better tolerated form of medication, particularly in patients demonstrating an adverse reaction or requiring a large VPA dosage. VPA dosage was successfully reduced in 15 patients who were seizure-free for > 2 years and had infrequent seizures before treatment, but 9 of 11 patients relapsed after VPA discontinuation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Juvenile myoclonic epilepsy: a 5-year prospective study. 815 46


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