To describe the time course of the six clinical stages of Lafora Progressive Myoclonus Epilepsy

Lafora Progressive Myoclonic Epilepsy or Lafora Disease (LD) is ultra-rare with a prevalence of less than 1 in 10,000,000. Due to its rarity, the full course of the disease and time course of progression remain poorly characterized.  Here we describe further refined criteria and detailed time-course for the six clinical stages of LD we have previously identified.

Stage I is a pre-seizure stage where the patient appears asymptomatic. However, extended video-EEG and neuropsychological testing may reveal subtle abnormalities. Stage II occurs with the onset of seizures at a mean age of 10.2 years (SD 2.9) in the total cohort with siblings and EPM2A patients reporting slightly earlier onset (though not significantly different).   Stage III occurs with beginning cognitive decline as reported by parents/teachers at age 13 (SD 1.4) and is not reliably detected by MoCA screening.  Stage IV occurs at mean age of 15.7 years (SD 1.1) with the first episode of status epilepticus (SE) and when cognitive decline has progressed to established dementia (MoCA <23 for all patients, MoCA <21 for majority of patients).  However, there is a subset of patients whose parents do not report any cognitive decline until after the first (SE).  Stage V occurs at mean age 17.6 years (SD 1.4) when the patient enters a state of myoclonic encephalopathy.  Stage VI occurs at mean age 19.5 years (SD 2.6) when the patient passes although this can be highly variable.