Early Abnormalities in Neurocognitive Domains in Lafora Disease

Document Type

Conference Proceeding

Publication Date

12-7-2025

Abstract

Rationale: Lafora Disease (LD) is an ultra-rare, progressive, and fatal neurodegenerative disorder. In LD, cognitive function is normal at baseline with rapid cognitive decline occurring a few years after seizure onset. However, LD is typically not diagnosed until cognitive impairment is already advanced. Subtle signs of cognitive impairment may be present earlier but not well ascertained. Our objective was to identify early abnormalities in neurocognitive domains in patients with LD. Methods: Cognition was assessed with Nasreddine’s Montreal cognitive assessment (MOCA) or Folstein’s mini-mental state exam (MMSE); A pediatric version of the MMSE was used for patients less than 12 years of age. Cognition was assessed at the time parents reported school academic regression or behavioral problems in 15 genetically confirmed EPM2A and EPM2B LD patients. Results: Six patients demonstrated MoCA scores between 22-26 at the time their parents first reported school problems or academic regression. In an additional 3 patients, the first report of school problems and regressing academic grades was combined with reports of behavioral problems (e.g. disagreeable, talking back to parents, physical fights). In these 3 patients, MoCA scores at the time of assessment was already below 20. Notably, in another six patients MOCA scores remained in the range of normal (27-30) despite parents reporting slipping grades. Abnormalities in neuropsychological domains as assessed by MoCA demonstrated an inability to draw the three dimensional character of a cube, failure to connect lines correctly in the visual-spatial executive sequential test, and decreased word production in one minute were the earliest alterations shared by these six patients. Conclusions: Abnormalities in neurocognitive domains are likely present early in LD patients. By the time parents report school problems, MoCA scores are already abnormal in more than half of the patients in this cohort. In our study, early abnormalities in neurocognitive domains were captured in the subset of patients who were still able to score >26 on the MoCA at the time parents reported school problems and suggests problems with visuospatial perception, motor planning, and executive function. Our findings suggest neurocognitive testing should be done earlier in LD patients (e.g. before symptoms are able to be detected to by parents) with more extensive neuropsychological tests as MoCA and MMSE are screening test which may be limited in their ability to detect early symptoms in LD.

Comments

American Epilepsy Society Annual Meeting, December 5-9, 2025, Atlanta, GA

Link to Full Text

Share

COinS