Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levetiracetam (LEV) has proven effective for partial seizures, suggesting the need to trial it in generalised epilepsy. Ten patients with generalised epilepsy were given compassionate use of LEV as a pilot study, attending 7 visits with seizure count (using diary) and compliance checked (pill count) with option for long term use. Seizure frequency was compared to baseline mean of the last 2 months and mean of follow-up. Patients were commenced on 500 mg I b.d, and titrated to a maximum of 3 g/day. There were 10 patients (7 females), aged 28-48, of whom 6 had primary generalised epilepsy (PGE) and 4 Lennox-Gastaut syndrome (LGS). At 7 month evaluation: 1 was seizure-free, 1 was 70% reduced, 3 were > or = 50% reduced, 2 were 30-35% reduced; 1 had no change; 1 was 10% increased and 1 was excluded because confounding pseudo seizures. Follow-up was 8-17 months (mean 13.8). The seizure-free patient became pregnant and had 2 seizures, but has been seizure-free for 2 months, at time of submission. A 16 months are three months seizure-free. One was 50% reduced at months 6 and 7, was 2 months seizure-free but then reverted to 50% per baseline. With respect to LGS, 1 withdrew due to aggression, 2 had 40% and 35% reduction at 13 and 15 months respectively and 1 had 25% increase (10% at 7 months). All patients were compliant. These data suggest that LEV may be effective for generalised epilepsy with a need for a larger clinical trial.
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PMID:A pilot study of compassionate use of Levetiracetam in patients with generalised epilepsy. 1533 34

Effects of the novel anti-epileptic drug levetiracetam (50 and 100 mg/kg) on spike and wave discharges (SWDs) of WAG/Rij rats were studied. Levetiracetam decreased the incidence, average duration, total duration and peak frequency of the SWDs. There was no difference between the two doses. These results agree with results obtained in Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Furthermore, the decrease of the SWD peak frequency might support the suggestions that levetiracetam might have a GABAergic mechanism of action.
Seizure 2004 Dec
PMID:Effects of levetiracetam on spike and wave discharges in WAG/Rij rats. 1551 20

Antiepileptic drugs exert their anticonvulsant effects by interfering with brain processes that involve structures that are also involved in learning, memory, and emotional behavior. Thus, modulation of ion channels, neurotransmitters, second messengers, and other processes by antiepileptic drugs, although helpful in controlling seizures, can interfere with normal brain function in undesired ways. The specific mechanism(s) of action of an antiepileptic drug can increase the risk for particular types of adverse events. In this review, we examine the cognitive and behavioral effects of antiepileptic drugs in animal models. Although animal studies, in many respects, do not mimic clinical experience, the data suggest a connection between certain mechanisms of antiepileptic action and the occurrence of cognitive adverse effects. Specifically, antiepileptic drugs with traditional gamma-aminobutyric acid (GABA)ergic mechanisms have the most detrimental effects on cognitive function, possibly because they impair attention. Conversely, drugs with the predominant effects at Na+ channels appear to have minimal impact on cognition. Levetiracetam, with its nonconventional GABAergic and Ca2+ channel effects, has shown positive cognitive effects in animal studies. Antiglutamatergic drugs have the potential to be a double-edged sword: they can interfere with consolidation of learning and memory but can also provide neuroprotection in addition to their antiseizure effects.
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PMID:Mechanisms of action for the commonly used antiepileptic drugs: relevance to antiepileptic drug-associated neurobehavioral adverse effects. 1552 66

Levetiracetam (LEV) is a novel antiepileptic drug (AED) with efficacy against a wide range of seizures types. The aim of this observational study was to assess its effectiveness in patients with mental retardation and refractory epilepsy. Sixty-four patients were started on adjunctive LEV after a 3-month baseline. LEV was initially dosed at 250 mg daily and increased by 250 mg every 2 weeks thereafter according to clinical response. Caregivers rated the patient's sleep, appetite, alertness, and behavior as poor (1), reasonable (2), or good (3) at each clinic visit. Patients were reviewed until one of four endpoints was reached: seizure freedom for at least 6 months, > or = 50% reduction in seizure frequency (responder) over a 6-month period, <50% reduction in seizure frequency (marginal effect) over a 6-month period, or LEV withdrawal due to lack of efficacy, adverse effects, or both. Twenty-four (38%) patients became seizure-free, 10 of whom were controlled on LEV 250 mg twice daily. An additional 18 (28%) patients were classified as responders, and 8 (12%) reported only marginal benefit from adjunctive LEV. Fourteen (22%) patients discontinued LEV (6 worsening seizures, 1 lack of efficacy, 7 adverse effects). Caregivers rated combined sleep, appetite, alertness, and behavior scores as "improved" at the end of follow-up (P<0.001). LEV improved seizure control in the majority of patients with mental retardation and may also have enhanced their quality of life.
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PMID:Levetiracetam for people with mental retardation and refractory epilepsy. 1558 36

We examined the efficacy, optimum dosage and adverse effects of levetiracetam in two prospective trials in children with epilepsy. In the add-on trial, 67 children between 6 months and 16 years were included. In the mono-therapy trial, 10 children between 4 years and 16 years were included. Levetiracetam was titrated up to an optimal dosage for every individual patient, depending on efficacy and tolerability, and reflecting clinical practice. The range of dosages used was between 12 and 62 mg/kg/day, with a median of 33 mg/kg/day. Overall, 20 weeks after the start of levetiracetam, there was a median seizure reduction of 60% (add-on trial 50%; mono-therapy trial 81%). Levetiracetam was equally effective for partial and generalized seizures. Side effects were less common in the mono-therapy trial. Tiredness (7.8%) and aggressiveness (5%) were the most common side effects, and were dose-related, but were no reason to discontinue levetiracetam. In 25% of the children, a positive effect was seen on behaviour and/or alertness. This could not be related directly to seizure control. Overall, these two clinical trials confirm that levetiracetam is a broad spectrum anti-epileptic drug with a favourable safety profile. The positive effect on behaviour needs further quantitative study.
Seizure 2005 Jan
PMID:Clinical experience with levetiracetam in childhood epilepsy: an add-on and mono-therapy trial. 1564 4

The purpose of this study was to assess the efficacy and safety of levetiracetam in a diverse pediatric epilepsy population. A retrospective chart review of 52 consecutive children age 8 months to 16 years who were treated with levetiracetam was performed. The data include patients with partial and generalized seizures, monotherapy, and concomitant antiepileptic drug use. Levetiracetam was dosed to efficacy or unacceptable side effects, with a range of 8 to 315 mg/kg/day. Two patients discontinued levetiracetam prior to assessment of efficacy owing to side effects. Of the remaining 50 patients, 12 had > or =75% seizure reduction, 3 had > or =50% and <75% seizure reduction, 8 had > or =25% and <50% seizure reduction, and 27 had < 25% seizure reduction. A variety of pediatric epilepsy syndromes and seizure types were represented. Adverse events, seen in 17 patients, were determined to be tolerable or resolved over time with continued dosing, dosage reduction, or discontinuation. This open-label, retrospective study of 52 consecutive pediatric patients treated with levetiracetam indicates at least partial efficacy in a variety of pediatric epilepsy syndromes. Tolerability was surprisingly favorable, even at doses far exceeding 40 mg/kg/day.
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PMID:Retrospective study of the use of levetiracetam in childhood seizure disorders. 1570 67

Seizures may occur after orthotopic liver transplantation. Antiepileptic drugs (AEDs) are used to treat these seizures, but the immunosuppressant regimen also may be altered. Levetiracetam is an attractive treatment because of its efficacy, lack of hepatic enzyme induction, and its rapid attainment of serum levels. Treatment with levetiracetam is efficacious, and levetiracetam-treated patients require significantly lower doses of immunosuppressant medications to achieve an equivalent antirejection effect.
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PMID:Levetiracetam for seizures after liver transplantation. 1578 37

Levetiracetam is a new antiepileptic drug whose efficacy and tolerability are already well known in adults. Few studies are available in children. This review, based on the international literature, aims to identify and make known the possible indications for levetiracetam in childhood. Most studies suggest that levetiracetam is effective against partial and generalized epilepsy. In resistant partial epilepsy, the percentage of responders reaches 64%, with 8 to 23% seizure free. Levetiracetam is used to treat symptomatic and idiopathic epilepsies. The drug has also proven effective against photosensitivity and epileptic and nonepileptic myoclonus. The most frequent side effects involve the behavioral sphere and manifest mostly in patients with a history of behavioral problems. In some patients, levetiracetam increases the number of seizures, but this adverse reaction can be partially avoided with slow titration. Doses for children should be 130 to 140% of those advised for adults. Levetiracetam seems to have a broad spectrum of action and is, on the whole, well tolerated. Its efficacy against generalized epilepsy is particularly promising in childhood.
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PMID:Levetiracetam in pediatrics. 1579 71

The aim of this multicentric, prospective and uncontrolled study was to evaluate the efficacy and safety of levetiracetam in 110 children with refractory epilepsy, of whom 21 were less than 4 years old. After a median follow-up period of 7 months, levetiracetam administration was effective (responders with >50% decrease in seizure frequency) in 39% of children, of whom 10 (9%) became seizure-free. The efficacy was higher in patients with localization-related epilepsy (58% of responders) than in those with generalized epilepsy (37% of responders). Levetiracetam was well tolerated. The main side effects of somnolence and irritability occurred in 14% of patients. In one patient acute choreoathetosis occurred after few doses of levetiracetam. Overall, the adverse effects were not severe. Children younger than 4 years were particularly tolerant. In conclusion, the present study confirms that levetiracetam is effective and well tolerated as an add-on treatment in children with refractory epilepsy. Our preliminary data also indicate that levetiracetam may be a valid therapeutic option for epilepsy in infants and young children.
Seizure 2005 Jun
PMID:Efficacy and safety of levetiracetam: an add-on trial in children with refractory epilepsy. 1591 59

Antiepileptic drug (AED) treatment is associated with multiple short- and long-term side effects. Effects on endocrine function, including weight change, reproductive function, thyroid function, and bone health are examples of these side effects. Some AEDs affect weight, resulting in weight gain or loss. Levetiracetam and lamotrigine are weight-neutral agents, whereas valproate is associated with weight gain. Reproductive dysfunction is reported in women and men with epilepsy treated with AEDs. In women, the most common symptoms are hyperandrogenism, menstrual disorders with ovulatory failure, polycystic ovary-appearing ovaries or polycystic ovary syndrome, and hyperinsulinemia. These symptoms may be secondary to epilepsy or to AED treatment, particularly with valproate. In men, effects on sperm quality and motility, delayed sexual development, and small testicular size have been described in association with AED treatment. Carbamazepine reduces testosterone levels, whereas valproate increases androgen levels. Oxcarbazepine is not associated with changes in testosterone levels. Treatment with all of these agents can result in changes in sperm, including concentration, morphology, and motility. Enzyme-inducing AEDs are known to result in decreased thyroid hormones. Recent studies found reduced serum thyroid hormone concentrations in men and young girls treated with carbamazepine and oxcarbazepine. However, all patients were clinically euthyroid, and these changes were reversible after AED withdrawal. Persons with epilepsy treated with AEDs are at increased risk for fracture. Not only is this increased because of seizure activity, but also because of treatment with AEDs. AED treatment results in decreased bone mineral density, the most sensitive predictor of fracture and changes in biochemical indices of bone metabolism, including calcium, vitamin D, and markers of bone formation and resorption. Identifying each of these endocrine abnormalities is important because it may be necessary and beneficial to change AED treatment. In addition, multiple therapies exist for the treatment of polycystic ovary syndrome, infertility, and decreased bone mineral density.
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PMID:Effects of Treatment on Endocrine Function in Patients with Epilepsy. 1596 90


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