Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

The efficacy of different regimens of therapy for parenchymal brain cysticercosis either with praziquantel (PZQ) or with albendazole (ALB) was compared in 114 patients. Four schemes of treatment were used: PZQ 50 mg/kg per day for 15 days, PZQ 50 mg/kg per day for 8 days, ALB 15 mg/kg per day for 30 days, and ALB 15 mg/kg per day for 8 days. Three months after therapy, it was apparent that both PZQ and ALB were effective, as shown by the disappearance of cystic lesions in computed tomographic scans. Thirty-three control patients followed for a mean of 11 months had no spontaneous remission of lesions. When comparing PZQ with ALB, the latter was found to be more effective than the former for both the full and the short course of treatment: 85% vs 60% and 85% vs 48% disappearance of lesions, respectively (P less than 0.001). Comparison of the full vs the short course of PZQ showed that the short course had a further 12% reduction in drug effectiveness. In contrast, the length of ALB therapy could be shortened without lessening its efficacy. Based on these results, an 8-day course of ALB is recommended as treatment for parenchymal brain cysticercosis; a 15-day course of PZQ could be subsequently used in those patients who show only partial response to ALB.

Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.

Twenty-six patients with cysticercosis of the brain parenchyma were treated with the antihelmintic agent praziquantel (50 mg per kilogram of body weight daily for 15 days). During treatment a strong inflammatory reaction occurred, as evidenced by increased protein and cells in the cerebrospinal fluid. This finding correlated with headache, exacerbation of neurologic symptoms, and edema and inflammation around cystic lesions. After three months of treatment all patients had improved clinically, and 13 (50 per cent) were asymptomatic. The total number of cysts on CT scans had decreased from 152 at the beginning of treatment to 51, and the mean diameter of cysts was reduced by 72 per cent. CT scans showed improvement in 25 of the 26 patients, with total remission of all cysts in nine. Seventeen control patients followed with CT studies for a mean of 9 +/- 2 months had no spontaneous remission of lesions, and in many cases the scans showed worsening during the observation period. Our results indicate that praziquantel is effective in cysticercosis of the brain parenchyma.