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Biomedical subjects

E Ben-Menachem

Publications and source records attributed to E Ben-Menachem.

At least 19 recordsLinked to original sources
PubMed2006

Levetiracetam: a long-term follow-up study of efficacy and safety.

OBJECTIVES: To evaluate the efficacy and safety of long-term add-on treatment with levetiracetam 1,000-4,000 mg/day. PATIENTS AND METHODS: In this multicenter, open-label follow-up study, 505 patients, from 10 European countries, who had benefited from previous add-on treatment with levetiracetam in a clinical trial or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most then continued levetiracetam by prescription or in a named patient program, where it was not yet commercially available. Mean treatment duration was 1,045 days (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250-6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years. RESULTS: Median total and partial seizure frequency per week over the evaluation period were 0.8 and 0.7; seizure frequency per week was generally stable over time and remained low. There was a probability of 6.6% of remaining seizure-free for the first 3 years, and of 18.9% of having a seizure-free period of at least 3 years at any time. Most adverse events were mild or moderate and unrelated to study drug. Levetiracetam was well tolerated, and provided stable seizure control during long-term treatment.

Adolescent↗
PubMed2006

Role of valproate across the ages. Treatment of epilepsy in adults.

A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability.

Adult↗
PubMed2005

EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task force.

Despite being a considerable problem in neurological practice and responsible for one-third of seizure-related admissions, there is little consensus as to the optimal investigation and management of alcohol-related seizures. The final literature search was undertaken in September 2004. Consensus recommendations are given graded according to the EFNS guidance regulations. To support the history taking, use of a structured questionnaire is recommended. When the drinking history is inconclusive, elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can support a clinical suspicion. A first epileptic seizure should prompt neuroimaging (CT or MRI). Before starting any carbohydrate containing fluids or food, patients presenting with suspected alcohol overuse should be given prophylactic thiamine parenterally. After an alcohol withdrawal seizure (AWS), the patient should be observed in hospital for at least 24 h and the severity of withdrawal symptoms needs to be followed. For patients with no history of withdrawal seizures and mild to moderate withdrawal symptoms, routine seizure preventive treatment is not necessary. Generally, benzodiazepines are efficacious and safe for primary and secondary seizure prevention; diazepam or, if available, lorazepam, is recommended. The efficacy of other drugs is insufficiently documented. Concerning long-term recommendations for non-alcohol dependent patients with partial epilepsy and controlled seizures, small amounts of alcohol may be safe. Alcohol-related seizures require particular attention both in the diagnostic work-up and treatment. Benzodiazepines should be chosen for the treatment and prevention of recurrent AWS.

Alcohol Withdrawal Seizures↗
PubMed2005

Data from regulatory studies: What do they tell? What don't they tell?

Phase III studies of antiepileptic drugs (AEDs) are specifically designed to satisfy strict regulatory criteria. As they are conducted in protocol-restricted patient populations over short treatment periods and employ fixed study designs and dosing schedules, they are not fully representative of 'real-life' clinical practice. Therefore, in order to provide an overall assessment of clinical performance, regulatory studies must be backed up by post-marketing clinical experience. Phase IV studies provide information on a drug's performance in a setting more closely representing real clinical practice, with broader patient populations and a more flexible approach to individual treatment. Prospective long-term studies allow the determination of efficacy and safety (and cost-effectiveness) over extended treatment periods; these studies and audit data provide a means of assessing idiosyncratic side effects, unusual interactions and the effects of an AED in rare patient groups. By complementing regulatory evidence with real-life clinical experience, a comprehensive assessment of the risks and benefits of an AED can be made.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Epilepsy: from consensus to daily practice.

Most clinicians would accept that epilepsy treatment should begin with monotherapy, and in the majority of cases this is the preferred drug maintenance option. The clinical choice of one antiepileptic drug (AED) over another should be based on firm evidence of efficacy and tolerability as evaluated in comparative monotherapy studies and pharmacokinetics. This paper presents the findings of evidence-based reviews of AED monotherapy in patients newly diagnosed with epilepsy. The main study was conducted in the United Kingdom and investigated the clinical evidence supporting AEDs used as first-line monotherapy. In this paper the general treatment recommendations will focus on valproate, one of the mainstay drugs used in the fight against epilepsy. Finally, with these recommendations in mind, the principles behind AED drug selection in clinical practice will be discussed. Factors for consideration that impact on AED decision-making include: seizure and syndrome diagnosis, AED tolerability profiles, patient characteristics and pharmacokinetic/pharmacodynamic AED interactions.

Adult↗
PubMed2002

Epileptic seizures, cranial neuralgias and paroxysmal symptoms in remitting and progressive multiple sclerosis.

The occurrence of a first epileptic seizure, spinal or brainstem paroxysmal symptom and cranial neuralgia during 25 years after onset was studied in a population-based multiple sclerosis (MS) cohort of 255 patients. Epileptic seizures occurred in 20, paroxysmal symptoms in 11 and cranial (trigeminal, intermedius, retroauricular or occipital) neuralgia in 11 patients. The yearly incidence of epileptic seizures in MS was estimated to be 349(+/-153)/100,000, approximately seven times higher than in the general population. The yearly incidence of a first paroxysmal symptom in the present material was calculated to be 190 cases in 100,000 MS patients, and the yearly incidence of cranial neuralgia was 189 cases in 100,000 MS patients. The epileptic seizures were more frequent during the progressive course than in the relapsing-remitting (RR) course. The frequencies of paroxysmal symptoms and cranial neuralgia did not differ between these two disease courses. A coincidence of epileptic seizures and a decline in cognitive functioning not seen among patients with paroxysmal symptoms was found The relatively late occurrence of epileptic seizures indicates that the frequency of epileptogenesis, known to involve neuronal damage, increases in the later stages of MS.

Adult↗
PubMed2001

Proof of efficacy trials: seizure types.

For proof of efficacy studies, ideally the seizure types included should also be the most common types of seizures so that an efficacy trial can recruit patients easily and in the shortest possible time frame, provide efficacy data that is valid for a large portion of the epilepsy population, include readily identifiable seizure types that are simple to count, and include seizures that occur frequently enough so that the trial can be short (3 months). Partial seizures are the most common seizure type in an adult population and therefore they represent the first choice for proof of efficacy studies, provided that data in experimental models support efficacy in this seizure type. Because there are already several antiepileptic drugs (AEDs) available which are effective for primary generalized seizure types, and patients with refractory primary generalized seizures are not so plentiful, and including these seizures as primary types to prove efficacy would be time consuming, expensive and therefore not feasible. It is concluded that, whereas proof of concept studies may include other seizure types, the first proof of efficacy studies should be undertaken in patients with frequent (>3/month) partial seizures.

Anticonvulsants↗
PubMed2001

Recent advances in the diagnosis and treatment of epilepsy.

Recent advances in the diagnosis and treatment of epilepsies are discussed with special consideration of epidemiology and classification, progress in neuroimaging, electrophysiological studies using EEG and MEG, initiation of medical and surgical treatment, the role of new antiepileptic drugs and selected aspects of genetics of idiopathic epilepsies. In addition from conclusions obtained by the review of recent developments suggestions for future work in Europe are discussed. A constructive approach from multicenter studies requires homologous definitions, documentations and standardization of procedures of trials for European multicenter studies.

Anticonvulsants↗
PubMed2001

Vigabatrin visual toxicity: evolution and dose dependence.

PURPOSE: To investigate the prevalence and prognosis of visual field defects (VFDs) in epilepsy patients with and without vigabatrin (VGB) treatment; to investigate the possible relationship between VFDs and cumulative VGB dose, and to characterise the evolution of VFDs. METHODS: A cohort of 155 presurgical candidates who had undergone full-field Goldmann perimetry (GP) was studied, 99 (64%) of whom had been treated with VGB. All GPs were reevaluated in 1998 by one experienced examiner, blinded to medication. Duration of treatment and total VGB dose were related to perimetric results. RESULTS: Twenty-five (16%) of the 155 patients had VFDs: Nineteen (19%) of the 99 VGB-treated patients, and six (11%) of the 56 patients unexposed to VGB. VGB-treated patients with VFDs had been treated significantly longer than those without VFDs. Cumulative VGB dose could be calculated for 84 patients. The prevalence of VFDs increased significantly with increasing total VGB-dose, from 4% in the 51 patients who had been exposed to <or=1 kg VGB, to 75% in the eight patients with a total dose of 3-5 kg of VGB. Sixteen VGB-treated patients were reexamined 2-10 years later. In the 12 where evaluation was possible, all still had VFDs, which had worsened in five cases (42%) and improved in none. CONCLUSIONS: This study indicates a strong relationship between VFDs and duration and total dose of VGB. VFDs were irreversible and in a substantial percentage progressive. Similar VFDs may, however, also be found in patients unexposed to VGB. A model of the evolution of the VFDs in VGB toxicity is introduced, and a new simple visual field test is proposed.

Adult↗
PubMed2001

Vagus nerve stimulation, side effects, and long-term safety.

Vagus nerve stimulation (VNS) is an accepted therapy for the treatment of refractory epilepsy and now even depression. More than 10,000 people have had the device implanted over a period of 12 years. Initial side effects in the early years such as lower facial weakness and electrode lead breaks have now been resolved. Postoperative infections occur in approximately 3% of patients but can be treated with oral antibiotics. Side effects during the use of VNS are usually related to the "on" phase of stimulation. Common side effects are cough, hoarseness, voice alteration, and paresthesias. These side effects tend to diminish with time. Cognitive side effects often seen with antiepileptic drug use are not reported. The side effect profile of VNS is positive, and this treatment option offers patients with refractory epilepsy prospects of good efficacy with only minor and often resolvable side effects.

Adult↗
PubMed2000

Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies.

Progressive myoclonic epilepsies (EPM) are difficult to treat and refractory to most antiepileptic drugs. Besides epilepsy, EPMs also involve continuous neurological deterioration. Oxidative stress is thought to be an important factor in this process. We therefore analyzed a series of antioxidant enzymes in the blood of patients and compared with healthy age matched controls. In addition patients were given high doses of N-acetylcysteine (NAC), a glutathione percursor to determine if symptoms of EPM would improve. Five patients, four with EPM 1 (Unverricht-Lundborg disease) and one patient with EPM2 (Lafora body disease) were treated with 6 g/day of NAC. Before treatment, plasma samples were analyzed for glutathione peroxidase activity, catalase activity, extracellular superoxide dismutase (SOD) and CuZn-SOD and compared with the controls. Erythrocyte CuZn-SOD was significantly lower in the EPM patients compared to controls. NAC improved markedly and stabilized the neurological symptoms in patients with EPM 1 but had a doubtful effect in the patient with EPM 2.

Acetylcysteine↗
PubMed2000

New antiepileptic drugs and non-pharmacological treatments.

Many new drugs and therapies can now be offered to patients with epilepsy. The problem is that we do not know just how much better these new and more expensive therapies are compared with the old ones, nor do we know the full range of side-effects. This review focuses on the major clinical studies that have been published in the past year with emphasis on information as to tolerability and efficacy, especially when there is some information comparing different drugs or therapies. The topics include vigabatrin, lamotrigine, gabapentin, felbamate, topiramate, tiagabine, oxcarbazepine, levetiracetam, vagus nerve stimulation and the ketogenic diet. It is encouraging that some of the newly published double-blinded placebo-controlled studies now include children and the elderly, patient groups that have previously been neglected.

Anticonvulsants↗
PubMed2000

Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included a maximum 12-week down-titration period and 12 weeks of monotherapy at 1500 mg twice daily. In both phases, responder rate, seizure frequency, and adverse events were analyzed. RESULTS: A total of 286 patients (placebo, n = 105; LEV, n = 181) entered the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received LEV completed the entire study compared with only 10 of 105 patients (9.5%) in the placebo group (p = 0.029). The odds of completing the study on LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; p < 0.001). In the LEV monotherapy group, the median percent reduction in partial seizure frequency compared with baseline was 73.8% (p = 0.037), with a responder rate of 59.2%. Nine patients (18.4%) remained seizure-free on LEV monotherapy. CONCLUSIONS: Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.

Anticonvulsants↗
PubMed1999

The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism.

OBJECTIVE: To investigate the effect of vigabatrin (VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with 18F-fluorodeoxyglucose (FDG) PET and 15O water PET. BACKGROUND: Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively. METHODS: Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline 18F-FDG and 15O water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test. RESULTS: No statistically significant difference in age, duration of epilepsy, or CBZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1+/-6.5% and global CBF by 13.1+/-10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p < 0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL). The increase differed from the PLC group (p < 0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R2 = 0.82, p < 0.01). CONCLUSIONS: Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism.

Adult↗
PubMed1999

Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years.

We assessed the long-term efficacy of vagus nerve stimulation (VNS) in 64 refractory epilepsy patients. After implantation, intermittent stimulation was delivered and seizure frequency and severity were counted. Average treatment time was 20 months. Nineteen of 47 patients with partial seizures, five of nine patients with idiopathic generalized seizures, and five of eight patients with Lennox-Gastaut syndrome had >50% seizure reduction. Side effects were mild. VNS is a safe and effective treatment for refractory epilepsy.

Electric Stimulation↗
PubMed1999

New antiepileptic drugs: comparison of key clinical trials.

PURPOSE: Data accrued from clinical trials of five new antiepileptic drugs (AEDs) are compared for efficacy in reducing seizures and self-reported adverse events as a basis of selection among new AEDs. Drawbacks to use of these data also are demonstrated. METHODS: A review of double-blind, placebo-controlled clinical trials of a new AED or placebo added to a standard AED provided data on reduction of complex partial seizures (CPSs). Success is > or =50% fewer CPSs with a new AED or placebo; Overall Improvement is the success rate with drug minus the success rate with placebo. Adverse events were tabulated from product-labeling lists of COSTART items (incidence, > or =5%). The Summary Complaint score is the total number of reports of individual events for each AED. RESULTS: Efficacy data demonstrate differences in Overall Improvement rates among five new AEDs and placebos (p = 0.001). However, rates of response to placebo also differed significantly among trials (p = 0.01). Adverse events predominantly affect central nervous system, psychiatric, and general body systems. However, patients in the placebo control groups did not consistently report adverse effects. Summary Complaint scores differ among the five new AEDs, but variability in use of COSTART terms nullifies comparisons. CONCLUSIONS: Comparisons of data for five new AEDs provide information for selection among treatments when a second drug is needed to improve control of CPSs. However, significant differences among the control groups and other problems make comparisons between trials problematic. The final choice should be based on the need of the individual patient for superior seizure control versus minimal adverse effects.

Acetates↗