Progressive Myoclonic Epilepsies - A Pragmatic Review

Progressive Myoclonus Epilepsy (PME) is a rare and complex group of inherited neurodegenerative disorders characterized by progressively worsening myoclonus, cognitive impairment, tonic-clonic seizures and ataxia. The clinical features and genetic underpinnings of PME are diverse, with approximately 80% of individuals now able to receive a molecular diagnosis. This review outlines the clinical phenotypes, genotypes, and management strategies for PME. Literature search for publications on PME in the preceding 20 years, with emphasis for the past one decade, performed using Medline, JSTOR (journal storage) and PubMed databases.

In PME progression of symptoms can vary widely among patients, with some experiencing rapid deterioration while others may have a slower rate of decline. Lafora Disease, characterized by the presence of Lafora bodies in tissues, Unverricht-Lundborg Disease (EPM1), caused by mutations in the CSTB gene, Myoclonic Epilepsy with Ragged-Red Fibers (MERRF), a mitochondrial disorder and Neuronal Ceroid Lipofuscinoses (NCL) make up the major chunk of PME syndromes. In the workup of PME, certain clinical and electroencephalogram (EEG) findings can help differentiate the specific etiologies. Valproic acid, perampanel, phenobarbitone and zonisamide are frequently prescribed as a treatment for various seizure types associated with PME. They are effective for managing both myoclonic and generalized tonic-clonic seizures. However, patients often have a progressive course and may find their myoclonus resistant to treatment.

This review explores the clinical features and genetic factors associated with the more prevalent as well as recently described forms of PME for effective clinical evaluation, and suggests management strategies for this challenging condition.