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A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group.

BACKGROUND: Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin. METHODS: We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred. RESULTS: For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001). CONCLUSIONS: Valproate is as effective as carbamazepine for the treatment of generalized tonic-clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects.

Adolescent↗

New antiepileptic drugs: into the new millennium.

There has been an explosion of new antiepileptic drug availability for physicians to treat patients with recurrent seizures. Principal antiepileptic drugs consisted of 6 key agents for both generalized and partial epilepsy for nearly 8 decades. Since 1993, the availability of newer "second-generation" agents has nearly doubled the armamentarium available for the 2.5 million patients who have recurrent seizures. This new influx of medications has flooded the medical and lay community with choices never before appreciated. The promise of improved tolerability with different safety and efficacy profiles has been exciting for all involved in epilepsy management. While most of the newer agents have been approved for adjunctive use in medically refractory partial epilepsy with recurrent complex partial and secondarily generalized seizures, efficacy is expanding to include generalized epilepsy and children for some agents. Arch Fam Med. 2000;9:1135-1141

Anticonvulsants↗

18F-labeled 2-deoxy-2-fluoro-D-glucose positron-emission tomography scans for the localization of the epileptogenic foci.

The localization of epileptogenic foci that are amenable to curative epilepsy surgery may be accomplished by noninvasive surface electroencephalogram (EEG) recordings, clinical observations, computed tomography (CT), magnetic resonance imaging (MRI), and neuropsychologic tests. Other tests, such as invasive EEG, 18F-fluoro-deoxyglucose-positron-emission tomography (FDG-PET or PET) scans, and single-photon-emission computed tomography (SPECT) scans, have also been used at various epilepsy centers to help identify candidates who might benefit from such surgery. Interictal PET scans have demonstrated hypometabolism in areas concordant with the epileptogenic foci indicated by other diagnostic tests such as EEG and MRI. However, PET scans have also shown no abnormality in many patients with EEG-indicated epileptogenic foci; in others, the scans have shown abnormal metabolism in areas that were discordant with the epileptogenic foci. Although substitution of the noninvasive PET scan for the invasive EEG recordings would be desirable, the available data were insufficient to determine whether PET scans might serve as a reliable substitute for EEG. A positive PET scan might contribute independent information for identifying the epileptogenic site but could be noncontributory or confusing when hypometabolism is not seen or is seen in presumably normal brain areas. It is not evident from the data in the literature to what extent confirmatory PET scan findings might contribute to the management of patients with complex partial seizures.

Electroencephalography↗

Vigabatrin in chronic epilepsy: a 7-year follow-up study of responder patients.

Data on efficacy and safety of vigabatrin over very protracted treatment periods are still limited. This study reports the follow up of 23 responder epileptic patients who continued vigabatrin treatment after completion of the first year, to an overall long-term exposure ranging 21-84 months (median 60; mean 58.0 +/- 24.0 sd). The seizure frequency during the follow up was compared with that at the end of the first year on vigabatrin. The rates of patients who gained a further improvement and those who deteriorated were almost identical, ranging 33-45% and 33-46% respectively at individual time points. At the trial endpoint, nine patients (39%) were improved, five (22%) were unchanged and nine (39%) showed some deterioration. All patients still had a 14-100% decrease of seizure frequency as compared with pretreatment baseline. Two patients discontinued vigabatrin for occasional reasons. No patient experienced new adverse events during the follow up after the first year on vigabatrin. No significant effects were noted on any of the routine hematologic or metabolic screening assessments. Although reduction of concomitant treatment was rarely possible, the overall number of associated antiepileptic drugs dropped from 42 at entry to 40 at the trial endpoint. These findings indicate that vigabatrin retains its efficacy and safety in responder patients for periods up to 7 years.

Adolescent↗

Gray matter heterotopia.

Gray matter heterotopia are common malformations of cortical development. From a clinical perspective, affected patients are best divided into three groups: subependymal, subcortical, and band heterotopia (also called double cortex). Symptomatic women with subependymal heterotopia typically present with partial epilepsy during the second decade of life; development and neurologic examinations up to that point are typically normal. Symptoms in men with subependymal heterotopia vary, depending on whether they have the X-linked or autosomal form. Men with the X-linked form more commonly have associated CNS and visceral anomalies; their development is typically abnormal. Symptomatic men with the autosomal variety have clinical courses similar to symptomatic women. Both men and women with subcortical heterotopia typically have congenital fixed neurologic deficits and develop partial epilepsy during the second half of the first decade of life. The more extensive the subcortical heterotopia, the greater the deficit; bilateral heterotopia are almost invariably associated with severe developmental delay or mental retardation. In general, band heterotopia are seen exclusively in women; men with a mutation of the related gene (called XLIS or DCX) usually die in utero or have a much more severe brain anomaly. Symptoms in affected women vary from normal to severe developmental delay or mental retardation; the severity of the syndrome is related to the thickness of the band of arrested neurons. Nearly all affected patients that come to medical attention have epilepsy, with partial complex and atypical absence epilepsy being the most common syndromes. Some of the more severely affected patients develop attacks.

Brain↗