Progressive Myoclonic Epilepsy

Progressive myoclonic epilepsies (PME) are a group of rare, inherited disorders characterized by seizures, myoclonus, and progressive neurological degeneration. Patients may also exhibit cerebellar ataxia, dementia, neuropathy, and myopathy. Myoclonic and generalized tonic-clonic seizures are most common, although absence, atypical absence, tonic, and focal seizures may occur. Myoclonus in PME occurs separately from seizures and may be focal or segmental and is often asymmetrical and arrhythmic.Myoclonic jerks are often precipitated by posture, action, or stimuli such as sound, light, or touch; they are most apparent on the face and distal extremities.The symptoms of PME typically begin in childhood or adolescence and the outcome is generally severe; however, the age of onset, rate of progression, and associated features depend on the PME subtype. In the early stages of PME, clinical and EEG features may mimic idiopathic generalised epilepsy syndromes, especially juvenile myoclonic epilepsy,but failure of therapy and progressive neurological and EEG deterioration point to a diagnosis of PME. A full history of the illness,developmental history in children, comprehensive family history when possible, and thorough clinical examination are imperative to obtain clues to diagnosis. Although laboratory and pathological studies are still required for some of the PME disorders, the revolution in molecular genetics has allowed a definitive diagnosis of some PMEs such as Unverricht-Lundborg disease, MERRF, DRPLA, and most patients with Lafora’s disease. Genetic evaluation panel usually includes 12 genes known to cause Lafora disease, Unverricht-Lundborg disease, the neuronal ceroid lipofuscinoses, and PRICKLE1-associated PME. These disorders are all inherited in an autosomal recessive manner. Treatment of PME disorders remains essentially that of managing seizures and myoclonus together with palliative, supportive, and rehabilitative measures. Commonly used antiepileptic drugs for management of myoclonus include combinations of valproic acid, benzodiazepines, phenobarbital, and more recently, piracetam, zonisamide, and levetiracetam.Care must be taken to avoid antiepileptic medications that clearly worsen myoclonus. These include vigabatrin, carbamazepine, phenytoin, and gabapentin. Lamotrogine has an unpredictable effect on myoclonus and must be used with caution.