Monotherapy with Valproate in Primary Generalized Epilepsies

Summary: Sodium valproate enteric-coated tablets were administered as monotherapy to 118 patients (median age, 19 years) with primary generalized epilepsies. More than half (56%) of these patients were transferred from prior drug therapy, most of them because of inadequate seizure control, and some because of adverse effects. Seventy-one percent of the patients experienced tonic-clonic seizures, either alone or in combination with other types of seizures, principally absences. Mean duration of follow-up was 18 months (median, 17 months; range, 1–68 months). At a mean daily dosage of <20 mg/kg, 83% of the patients became seizure-free. Therapy was equally effective against tonic-clonic seizures, absences, and myoclonic seizures. Tonic-clonic seizures were suppressed in 85% of cases (89% when patient had only one seizure type), absences in 82% (95% when patient had only one seizure type), and myoclonic seizures in 82%. Paroxysmal activity was present in 88% of the electroencephalogram (EEG) records before valproate monotherapy, and in 32.4% at the study's end. These results were achieved with generally mild and mostly transient side effects; side effects were reported by 16% of patients during the first month, and 2% at the last follow-up. No hematologic or hepatic toxicity was observed. The lag time between attaining steady-state serum concentrations and achieving maximal clinical improvement suggests that sodium valproate monotherapy should be given an adequate trial to ensure that patients derive the greatest possible benefit before adding or switching to another drug.     

Clinical experience with zonisamide monotherapy and adjunctive therapy in children with epilepsy at a tertiary care referral center

We evaluated our clinical experience with zonisamide, a broad-spectrum antiepileptic drug, in a group of children with predominantly medically refractory epilepsy. A retrospective chart review was conducted on patients at our tertiary referral center following Institutional Review Board approval. Observers documented reports of seizure frequency, and seizure types were identified either clinically or by prior video-electroencephalography monitoring. We identified 68 patients (age range 1.9-18.1 years [median 6.9 years]; male to female ratio 1.3:1) treated with zonisamide for 0.7 to 28.9 months; at the last visit, 22% and 78% were on monotherapy and adjunctive therapy, respectively. The median duration of treatment and maintenance dose at the end of the follow-up were 11.2 months and 8.0 mg/kg/day, respectively. Seizure types included generalized (primary generalized tonic-clonic, myoclonic, tonic, atonic, absence) and partial (simple, complex, and secondarily generalized tonic-clonic seizures); 10 (15%) patients had both partial and generalized seizures. Sixteen (25.8%) patients were seizure free, although five of them were already in remission prior to starting zonisamide. Thirteen (21.0%) patients had a > 50% seizure reduction, 10 (16.1%) patients had a < 50% seizure reduction, 14 (22.6%) had no improvement in baseline seizures, and 9 (14.5%) reported having increased seizures. The latter were mostly associated with dosage alterations in concomitant antiepileptic drugs. Common side effects were central nervous system related, including behavioral or psychiatric (23.5%), cognitive dysfunction (12.0%), and sedation (10.3%). Eleven (16.2%) patients ultimately discontinued zonisamide, but only five were strictly due to side effects. Zonisamide is clinically effective against multiple seizure types in a significant proportion of children with epilepsy across a broad age range. Drug discontinuation as a result of side effects is uncommon.     

Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability

The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.     

Amantadine hydrochloride for refractory generalized epilepsy in adults

Amantadine hydrochloride has been shown in several open studies to benefit children with refractory generalized epilepsy. We used amantadine as adjunctive therapy in 10 adolescents and adults with generalized tonic-clonic, myoclonic, or absence seizures refractory to therapeutic levels of valproate, carbamazepine, phenytoin, and benzodiazepines. Seven patients were men and 3 were women aged 18-29 years, and 8 of 10 patients were mentally retarded. All patients had generalized epileptiform paroxysms on EEG, with generalized or absence seizure recorded in 9. Five patients had both absence and tonic-clonic seizures, and 2 had all three seizure types. Amantadine was added to the existing regimens in weekly increments to 400 mg/day. Two patients had greater than 90 per cent seizure reduction, both with vomiting and somnolence. Two patients had seizure reduction between 50 and 90 per cent, 1 with anorexia and sleepiness. Three patients had no change in seizures, and 3 had worse tonic-clonic seizures. Amantadine may have some antiepileptic efficacy of unknown mechanism, but it may worsen generalized tonic-clonic seizures and is likely to be of limited value in adults.     

Lamotrigine and valproate: efficacy of co-administration in a pediatric population

This study aimed to assess the risks and benefits of the co-administration of lamotrigine and valproate in a pediatric population with refractory epilepsy. Twenty-eight children who received lamotrigine and valproate during co-medication were evaluated. Outcome measurements were established according to efficacy in seizure control, adverse effects, and tolerability. Treatment was considered effective when >50% frequency reduction was obtained. Adverse effects were also analyzed and in patients who presented them the mode of administration was compared with those who did not to verify the importance of this factor. Association of lamotrigine and valproate was considered effective in 64.3% of all patients, regardless of the seizure type. Seizure-free status was obtained in six patients. Drop attacks and secondary generalized tonic-clonic seizures were reduced in five patients, who remained under treatment despite less than the satisfactory (<50%) seizure decrease. Tremor occurred in six patients; urinary incontinence and ataxia in one. Skin rash also occurred, as an early manifestation, in two patients, both with a previous history of hypersensitivity to antiepileptic drugs. Causes for discontinuation were inefficacy of treatment in six patients and presence of adverse effects in two. In our series, seizure control was obtained in most children with refractory epilepsy, some of whom had a previous history of unsatisfactory response to lamotrigine and valproate, either in monotherapy or polytherapy. Adverse effects were uncommon, but skin rash was observed in higher proportions than in other series with lamotrigine or valproate. Nevertheless, these risks may be lessened with slow introduction and by exclusion of patients with a previous history of hypersensitivity.     

Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.

Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.     

Use of topiramate in childhood generalized seizure disorders

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children.     

Selection of drugs for the treatment of epilepsy

Antiepileptic drug selection is based on efficacy for specific seizure types and epileptic syndromes. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the drug of choice is valproate. Secondary generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single drug or combination of drugs. The drugs of choice for absence seizures are ethosuximide and valproate. For control of tonic-clonic seizures, any of the other major antiepileptic drugs can be effective. If valproate cannot be used, carbamazepine, phenobarbital, phenytoin, or primidone is effective, but ethosuximide or a benzodiazepine needs to be added to control associated absence or myoclonic seizures. The drugs of first choice for partial epilepsies with partial and secondarily tonic-clonic seizures are carbamazepine and phenytoin. Increasing evidence suggests that valproate may be a third alternative. Phenobarbital and primidone are second choice selections because of side effects. A combination of two of these five major antiepileptic drugs may be necessary for inadequately controlled patients. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, and alcoholic epilepsy require specific drug treatment. For all these seizure types and epilepsy syndromes, treatment ultimately must be selected to provide maximal efficacy and minimal adverse effect for each individual patient.     

Outpatient sleep recording during antiepileptic drug monotherapy

The effects of sleep and sleep deprivation on epilepsy are well known, but the effects of seizures and antiepileptic drugs (AEDs) on sleep have been less well studied. We recorded nocturnal sleep in 17 patients receiving antiepileptic monotherapy with ambulatory cassette EEG devices. Twelve patients had complex partial seizures and five had tonic-clonic convulsions. Two patients' seizures were largely nocturnal, and no seizures occurred during sleep recording. Five patients each were taking phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), and two were taking clonazepam (CZP), all with therapeutic serum levels and no toxic symptoms. Total sleep time was reduced, wakefulness increased, and sleep latency prolonged in partial seizures as compared with generalized epilepsy. REM sleep was reduced and its latency decreased in partial seizure patients. Both groups had decreased slow wave sleep; that of partial seizure patients was decreased more markedly. PHT increased sleep latency and decreased sleep time, and CBZ increased awakening and diminished slow wave and REM sleep. Patients taking VPA had slight reduction in slow wave sleep; those taking CPZ had decreased sleep and REM latencies. Epilepsy may affect nocturnal sleep, and the effects of partial and generalized seizure disorders may be different. AEDs may also have differential effects on nighttime sleep. These may prove important in the long-term management of epileptic patients.     

Epilepsia y gestación. Factores asociados con la presencia de crisis en la gestación

IntroductionThe management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs.ObjectivesThis study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiepileptic drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018.MethodsWe conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables.ResultsA total of 101 pregnancies were included. Patients’ mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs. 15.1%; P < .001), treatment with 2 or more antiepileptic drugs (30% vs. 14.8%; P < .001), and untreated epilepsy (25% vs. 0%; P < .001). The antiepileptic drugs most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion patients receiving monotherapy (81.5%, vs. 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs. 23.1%) and valproate (20.5%, vs. 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs. 0%).ConclusionsThe factors associated with the presence of seizures during pregnancy were previous poor seizure control, treatment with 2 or more antiepileptic drugs, and lack of treatment during pregnancy. The most commonly used drugs were lamotrigine, valproate, and levetiracetam, with an increase in levetiracetam use and a decrease in valproate use being observed in the later period (2011-2018).     

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an 相似文献   

Excellent results with clorazepate in recalcitrant childhood epilepsies

Eleven children with severe incapacitating generalized seizures were treated with sodium valproate and clorazepate and responded with a marked decrease in seizure frequency. Three children received clorazepate alone, either because of valproate toxicity or because of parental concern over side effects. These children, 5 males and 6 females, ranged in age from 3 to 17 years. They manifested normal to severely retarded intelligence. Although valproate levels were in the therapeutic range, seizure control was inadequate. When clorazepate was added to valproate therapy a marked reduction in seizure frequency occurred within 24 hours and became optimal within 48 to 72 hours. Side effects were minimal with the exception of a nocturnal generalized tonic-clonic seizure in a single patient. Three children were withdrawn from therapy after a year because of recurrent seizures. One patient was restarted on therapy after 6 months and seizure control improved. Clorazepate may be a useful adjunct in the treatment of primary generalized seizures in children.     

Sodium Valproate: Monotherapy and Polytherapy

Summary: Of the 605 patients seen since 1973, 336 patients have been treated with sodium valproate (VPA) alone or in combination with drugs other than carbamazepine (CBZ). Of these 336, 240 have been on monotherapy, of whom 200 are seizure-free. Follow up has been longer than 3 years in 78%. Complete control of seizures has been achieved in more than 80% of patients with absence, myoclonic, and primary tonic-clonic seizures, in 72% of those with photosenstivie epilepsy including eyelid myoclonia, and in 47% of partial epilepsies, for which carbamazepine was the initial drug of choice. Only 21% of those with myoclonic astatic epilepsy have become free from seizures. At first VPA was given twice daily, but in recent years it was given once daily, as this was more effective. Reasons for failure of VPA therapy are given. Side effects in 436 patients (100 more patients were added for this assessment only) were uncommon, though where they did occur, weight increase was the most frequent. Platelets were reduced without clinical problems. There were no severe hepatic disorders. Serum levels were assessed in seizure-free patients, and the optimum level was between 60 and 120 mg/L (most patients received between 20 and 30 mg/kg). VPA was given during 30 pregnancies, and there was no evidence of teratogenicity on monotherapy. VPA is most effective in primary generalized epilepsy, especially if given as the sole antiepileptic drug. If the daily dose does not exceed 40 mg/kg or 2.5 g, it is singularly free from serious side effects.     

Efficacy and tolerability of conversion to monotherapy with lamotrigine compared with valproate and carbamazepine in patients with epilepsy

OBJECTIVE: This randomized, open-label study was designed to compare the efficacy and tolerability of lamotrigine monotherapy with those of valproate and carbamazepine monotherapy in patients with epilepsy whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy. METHODS: Patients meeting eligibility criteria were randomized 2:1 to lamotrigine:carbamazepine or lamotrigine:valproate. The treatment phase was divided into a 4-week dose-escalation phase (Weeks 1-4), during which lamotrigine, carbamazepine, or valproate was added to patient's prestudy monotherapy; an 8-week add-on phase (Weeks 5-12), during which patients were stabilized on both the study medication and their prestudy antiepileptic therapy; an 8-week withdrawal phase (Weeks 13-20), during which prestudy antiepileptic therapy could be withdrawn if clinically appropriate; and an 8-week monotherapy phase (Weeks 21-28), during which patients could be treated with study medication as monotherapy. RESULTS: The numbers of patients randomized to the carbamazepine and valproate arms of the study were 144 (98 lamotrigine, 46 carbamazepine) and 158 (105 lamotrigine, 53 valproate), respectively. Successful monotherapy sustained for at least 7 weeks was achieved in comparable percentages of patients in the lamotrigine group (56%) and the carbamazepine group (54%) and in more patients in the lamotrigine group (49%) than the valproate group (40%). Among monotherapy completers, the percentage of patients with zero seizures during the monotherapy phase was comparable for lamotrigine (41%) and carbamazepine (30%) and significantly higher (P<0.05) with lamotrigine (32%) than with valproate (11%). No differences between treatments were observed with respect to time to treatment failure or time to first seizure. Lamotrigine was also better tolerated than carbamazepine or valproate. CONCLUSION: Lamotrigine monotherapy was as effective as and better tolerated than carbamazepine or valproate monotherapy in patients whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy.     

Efficacy and tolerability of antiepileptic drugs in an Omani epileptic population

OBJECTIVE: The aim of this hospital-based study is to get an insight into the efficacy and tolerability of antiepileptic drugs (AED) in Omani epileptic patients. PATIENTS AND METHODS: All Omani patients (aged 14 years and above) suffering from epileptic seizures for at least 2 years and followed-up by board-certified neurologists in Sultan Qaboos University Hospital (SQUH) were evaluated. The treatment retention rate since first visit at SQUH and over the last 2 years was used as primary efficacy measure of AED therapy. Change in seizure-frequency and side effect profiles were also assessed. RESULTS: In this population of 203 confirmed epileptic patients, generalized tonic-clonic (40%) and partial seizures (39%) were most commonly observed, idiopathic/cryptogenic origin (81%) being the most frequent encountered origin. Sixty one percent of the patients were controlled with an AED in monotherapy and overall 34% of patients could be successfully maintained on monotherapy during the whole follow-up period at SQUH (median 6 years). The treatment retention rates for carbamazepine (CBZ) at a daily dose of 400-600 mg, sodium valproate (VPA) at a daily dose of 500-1000 mg, and phenytoin (PHT) at a daily dose of 300 mg, in monotherapy over the total follow-up period was 51, 50, and 21%, respectively. In contrast, over the last 2 years these rates were highest for VPA (91%) followed by CBZ (83%) and PHT (73%). Adverse drug reactions were recorded in 67% of patients, and were most commonly encountered with VPA. CONCLUSIONS: Despite a higher adverse effect profile for VPA, long-term treatment with CBZ and VPA appeared to be equally effective in terms of treatment retention rates and seizure control.     

Felbamate monotherapy: controlled trial in patients with partial onset seizures.

Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single-center, randomized, double-blind, parallel-group trial. During the 56-day baseline period, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one-third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria. Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in highest 2-day seizure frequency, single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria (p less than 0.001, chi-square test). When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile.     

Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study

We studied the antiepileptic potency of vigabatrin (gamma-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.     

Total or partial withdrawal of antiepileptic drugs

Total withdrawal of antiepileptic drugs leads to a mean relapse rate of approximately 50 p. 100 in adults and 25 p. 100 in children. The relapse rates are lowest in patients with benign epilepsies of childhood and epilepsies with absence seizures only and those with a short duration of epilepsy. Relapse rates are higher in patients with complex partial seizures, absences with generalized tonic-clonic seizures, juvenile myoclonic epilepsy, patients with several types of seizures, high seizure frequency prior to control, in patients with neurological, psychiatric or social handicaps and in those with emotional ambivalence towards the reduction. Guidelines for slow and safe withdrawal are given. Reduction should be actively encouraged only in patients with absence seizures or benign focal epilepsy and those with epilepsy of short duration. Slow partial withdrawal is recommended in uncontrolled epilepsy because in 80 p. 100 of the patients it results in a decrease in seizure frequency and side effects or both.     

Epilepsy and antiepileptic drug therapy in juvenile neuronal ceroid lipofuscinosis

PURPOSE: To survey the characteristics of epilepsy in patients with juvenile neuronal ceroid lipofuscinosis (JNCL) and determine the antiepileptic drug (AED) treatment most suitable for these patients. METHODS: The study included 60 patients with JNCL; their mean age was 16.5 years (range 5-33). The age at onset of epilepsy, type of seizures, effect of the first AED on seizures, and the current seizure frequency and AED therapy were studied. The side effects of the AEDs were also clarified. RESULTS: Fifty of the 60 patients had epilepsy. Patients' first epileptic seizure occurred at a mean age of 10.0 years (range 5-16), the most common type being generalized seizures. As the first AED tried, valproate (VPA) and lamotrigine (LTG) appeared equally effective, with 80% of the patients responding to these AEDs. During the study year, the median seizure frequency was four seizures a year (range 0-120), and 72% of the patients had good or satisfactory seizure control (0-6 seizures a year). In the different AED therapy groups, the proportion of patients with good or satisfactory seizure control ranged from 25% to 100%. LTG in monotherapy or in combination with clonazepam (CZP) was superior to other AEDs or combinations, but VPA also seemed effective. Adverse effects leading to the discontinuation of an AED were observed in 25% of the patients, most frequently in patients receiving phenobarbital (PB). No patient receiving LTG had to discontinue the drug due to adverse effects. CONCLUSION: Epilepsy in JNCL can usually be successfully treated with the current AEDs. In Finnish patients with JNCL, treatment is based on LTG, or, secondarily, VPA. In combination therapy, CZP seems a valuable add-on AED.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.