Sleep and Awake EEG Findings in a Patient With Lafora Disease: From Presymptomatic to Overt Disease Stage.

Objectives: Lafora disease (LD) is a fatal progressive myoclonic epilepsy, characterized by disabling myoclonus, intractable seizures, and progressive cognitive decline. At the onset of symptoms, however, distinction from idiopathic generalized epilepsies may be difficult based on EEG because the background activity is typically preserved and the only abnormalities are rare generalized spike-and-wave discharges facilitated by the intermittent light stimulation. This underscores the urgent need for early biomarkers of the disease, particularly as disease-modifying therapies are being developed.

Methods: We describe the 24-month course of a patient with LD, whose older brother was similarly affected, followed up from the presymptomatic to overt disease stage. At each time point, the patient underwent neurologic, neuropsychological, and neurophysiologic evaluations, including an assessment of nocturnal sleep.

Results: During the first, presymptomatic assessment, when the patient was 13 years old, we documented generalized spike-and-wave discharges during rapid eye movement (REM) sleep, a very atypical finding for generalized idiopathic epilepsies, whereas wake EEG was substantially normal.

Discussion: This case study shows that neurophysiologic changes (wake and sleep EEG) showed early alterations even in the absence of motor and cognitive impairment, implying that an early diagnosis in patients with LD might have important implications for targeting future therapeutic strategies.