Unusual Course of Lafora Disease

Abstract

A 42-year-old male was admitted for refractory status epilepticus. At the age of 25, he had been diagnosed with juvenile myoclonic epilepsy. He had a stable clinical course for over a decade until a recent deterioration of behavior and epilepsy. After exclusion of acquired disorders, diagnostic work-up included application of next-generation sequencing (NGS), with a gene panel targeting progressive myoclonic epilepsies. This resulted in the diagnosis Lafora disease resulting from compound heterozygous NHLRC1 pathogenic variants. Although these pathogenic variants may be associated with a variable phenotype, including both severe and mild clinical course, the clinical presentation of our patient at this age is very unusual for Lafora disease. Our case expands the phenotype spectrum of Lafora disease resulting from pathogenic NHLRC1 variants and illustrates the value of using NGS in clinical practice to lead to a rapid diagnosis and guide therapeutic options.

Keywords: Lafora disease; Myoclonus epilepsy; Next‐generation sequencing; Refractory status epilepticus.

Figure 1

Diagnostic investigations of patient with Lafora disease. (A) The left panel shows 8 s of raw EEG and electromyography (EMG) data of muscles of the right leg. Note the short duration of the EMG bursts. The EEG shows no epileptic abnormalities. The middle panel shows a clear positive‐negative potential in the central electrode after back averaging, which starts approximately 40 ms before myoclonus onset. Right panel: Topographic mapping of the cortical potential. (B) Three consecutive brain MRIs (transversal sections). The left and middle slices show diffusion weighted images (DWIs); the right image is based on fluid attenuation inversion recovery (FLAIR) sequences. The first MRI shows hyperintensity of the gyrus cinguli corresponding to the maximum of seizure activity. The second MRI shows extension of the gray matter abnormalities likely associated with repeated periods of epileptic seizure activity. The third MRI shows complete disappearance of the abnormal T2 hyperintensity of the gray matter. (C) The left panel shows a hematoxylin and eosin (H&E) stain overview of the axillary biopsy. The right panel shows a detailed periodic acid Schiff staining with multiple Lafora bodies (arrows) in the myoepithelial cells surrounding the glands.