Clinical Stages of Lafora Progressive Myoclonus Epilepsy

Authors

• Viet-Huong Nguyen
• Reyna M. Duron
• Iris E. Martinez-Juarez
• Douglas R. Nordli III
• Maher Riad Arabi
• Deborah Holder
• Arthur Partikian
• Nancy McNamara, Corewell Health East
• Julia Henry
• Esther Tantsis
• Rene Silva Somaza
• Mitchell Williams
• Dawn Eliashiv
• Berge Minassian
• Jose Maria Serratosa Fernandes
• Antonio Delgado-Escueta

Document Type

Conference Proceeding

Publication Date

6-9-2026

Publication Title

Neurology

Abstract

Objective: To describe the time course of the six clinical stages of Lafora Progressive Myoclonus Epilepsy. Background: 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. Design/Methods: Twenty-five genetically confirmed EPM2A/EPM2B LD patients were followed in a prospective/ longitudinal observational cohort study. Outcomes were stratified by genotype and sibling-proband status. Results: 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. Conclusions: We have established six clinical stages of LD and described time-course of progression, Notably, there a pre-seizure stage which may present with subtle symptoms and merits further investigation.

Volume

106

Issue

11 Suppl 1

First Page

4550

Comments

American Academy of Neurology Annual Meeting, April 18-22, 2026, Chicago, IL

Last Page

4550

Recommended Citation

Nguyen VH, Duron RM, Martinez-Juarez IE, Nordli III DR, Arabi MR, Holder D, et al. [McNamara N]. Clinical stages of Lafora progressive myoclonus epilepsy. Neurology. 2026 Jun 9;106(11 Suppl 1):4550. doi:10.1212/WNL.0000000000217206

DOI

10.1212/WNL.0000000000217206