This chapter describes the differential diagnosis, treatment, and outcome for severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS). The frequency of convulsive seizures seems to correlate with the severity of developmental delay, suggesting that DS might be considered as a true epileptic encephalopathy. The frequency of detectable mutations in DS is around 70-80%; truncating mutations account for nearly 50% of the abnormalities with the remaining comprising splice-site and missense mutations. The repetition of febrile seizures and/or the prolonged convulsions with unilateral clinical features are clues orienting towards a diagnosis of DS. Children may manifest myoclonic seizures at onset and be misdiagnosed as having benign myoclonic epilepsy of infancy. Valproic acid, benzodiazepines, and topiramate have been proven to have some efficacy. Mortality rates are at around 16%, mainly as a result of sudden death or seizure-related accidents.

The progressive myoclonus epilepsies (PMEs) are a rare group of disorders with varied causes manifested by myoclonus, often activated by movement or action, but also occurring at rest. The form of PME is particularly striking in many family members affected by autosomal dominant Alzheimer disease linked to chromosome 14. The presenting features are cognitive decline with prominent seizures and myoclonus. Myoclonus is frequently described as an early feature of patients with amyloid precursor (16) protein gene mutation pedigrees who have limb dyspraxia, brisk reflexes, visual disorientation, and slow gait. Toxic causes of myoclonus include the sialysis syndrome characterized by myoclonus, asterixis, speech disorder, seizures, personality changes, and progressive dementia. The use of serotonin reuptake inhibitors commonly used as antidepressants may lead to severe myoclonus described with the use of citalopram and risperidone. Cephalosporin toxicity, levetiracetam accumulation in renal failure, amlodipine and nifedipine can induce acute myoclonic jerking without convulsive seizures.