Progressive Myoclonic Epilepsies: Definitive and Undetermined Causes

In the February 4, 2014, issue of the journal Neurology ahead of press, Dr. Franceschetti and colleagues representing a large consortium in Italy present an evaluation of progressive myoclonic epilepsies.

• During the study, 25 Italian epilepsy centers contributed patients and the information regarding those patients to to understand the underlying causes of progressive myoclonic epilepsy.
• The study included 204 patients: 77 with a diagnosis of Unverricht-Lundborg disease, 37 with a diagnosis of Lafora body disease, and 31 who had progressive myoclonic epilepsies due to rare genetic causes, mostly neuronal ceroid lipofuscinosis. Two more patients had celiac disease. No definitive etiology was found for 57 patients.
• Cluster analysis indicated that patients could be grouped into two clusters defined by age of onset.
• These two clusters have the following characteristics.
  • Patients in the first cluster experience early onset of disease and myoclonus whereas those in a second cluster experience more variable but predominantly late-onset myoclonus and other neurologic symptoms.
  • Moreover, cluster I includes more patients in whom psychomotor delay precedes the appearance of cortical myoclonus, e.g., paroxysms evoked by intermittent photic stimulation and atrophic changes in the cerebellar and cerebral cortex.
  • Cluster II patients have associated signs that exceed typical progressive myoclonic epilepsies.
  • Recurrent and polymorphic seizures were more common in cluster I; whereas almost half of the patients in cluster II had no seizures other than myoclonic.
• The authors conclude that there are many different varieties of progressive myoclonic epilepsy and that the phenotypes of the patients vary widely. There appears to be two separate clusters suggesting novel forms of progressive myoclonic epilepsy that are yet to be clinically and genetically described.