Abstracts

The progressive myoclonus epilepsies (PMEs) are a group of symptomatic generalized epilepsies with a progressive course and poor outcome. Advances in molecular genetics have begun to elucidate the causes of PME, including Lafora disease, Unverricht Lundborg disease, neuronal ceroid lipofuscinoses, dentatorubral-pallidoluysian atropy (DRPLA) and myoclonic epilepsy with ragged red fibres (MERFF). We report EIF2B related leucodystrophy (leucoencephalopathy with vanishing white matter/childhood ataxia with central nervous system hypomyelination) as another cause of PME. Detailed medical and family histories were obtained on the proband and his relatives. EEG, MRI and MRS of the brain, EMG, MRS of the muscle, skin-muscle-nerve biopsy, brain biopsy, bone marrow biopsy, CSF studies, metabolic work-up and molecular genetic studies for MERFF, DRPLA, spinocerebellar ataxia type 1 and 3, and vanishing white matter leucodystrophy were performed on the proband. The proband, a 38 year-old man, started having learning problems at age 9, after a head trauma with loss of consciousness. At age 22, he started to have myoclonic jerks as well as generalized tonic-clonic seizures. At age 38, he had a cerebellar syndrome with severe dysarthria, bilateral jerky pursuits, dysmetria, and ataxia, as well as a bilateral pyramidal syndrome including increased muscle tone most pronounced in the lower limbs, with bilateral Babinski signs. He was wheelchair bound since age 31. The myoclonus (rest, posture and action) that had been very disabling in his twenties had almost disappeared, but he still had some action myoclonus of low amplitude, as well as negative myoclonic jerks of the arms. Infrequent brief generalized seizures persisted. He was treated with gabapentin, phenobarbital and lamotrigine. A severe pancreatitis was attributed to valproic acid. MRI showed marked selective loss of white matter volume with extreme thinning of the corpus callosum. Brain biopsy revealed evident loss of white matter. EEGs showed high amplitude delta activity from both hemispheres, absent alpha rhythm and a moderate amount of bilateral independent intermittent sharp and slow wave activity from both temporal lobes. The proband was homozygous for the R113H mutation in the EIF2B5 gene. Mutations in any of the 5 genes encoding subunits of the translation initiation factor eIF2B can cause vanishing white matter leucodystrophy /childhood ataxia with central nervous system hypomyelination. Mutations in the EIF2B5 gene and possibly also in the 4 other genes, should be included in the differential diagnosis of progressive myoclonus epilepsy. (Supported by The Savoy Foundation for Epilepsy Research.)