Authors :
Presenting Author: Jelena Hyppönen, MD, PhD – Kuopio University Hospital
Reetta Kälviäinen, Prof – Kuopio University Hospital; Esa Mervaala, Prof – Kuopio University Hospital; Laura Säisänen, PhD – Kuopio University Hospital; Katri Silvennoinen, MD – Kuopio University Hospital
Rationale:
Patients with progressive myoclonus epilepsy type 1 (EPM1) have generalized tonic-clonic seizures and disabling action activated myoclonic jerks. The epileptiform discharges (EDs) described in EPM1 are usually generalized spike or polyspikes-and-wave discharges that are precipitated by photostimulation. They can occur interictally or can be related to cortical myoclonus. On the other hand, patients experience subcortical action myoclonus without time locked EDs. The EDs are common during wakefulness and decrease over the years. We aimed to characterize and quantify EDs during wakefulness and different sleep stages as well as correlate ED findings with clinical parameters in Finnish EPM1 patients.Methods:
Twenty genetically confirmed EPM1 patients (7M, 13F, aged 28.8 ±8.2 years) underwent overnight polysomnography (PSG), which included 19-channel EEG, standard polysomnographic channels and video. Additionally, one day ambulatory EEG including overnight recording was performed for additional eight EPM1 patients (2M, 6F). The ambulatory EEG recording included also chin EMG-channel for identification of REM-sleep. The sleep stages from the PSG recordings were manually scored and IEDs visually identified in both PSG and ambulatory EEGs. In the PSG recordings the epochs containing at least one ED were counted. Obtained results were correlated with the clinical characteristics and myoclonus severity assessed using Unified Myoclonus Rating Scale (UMRS). Results:
In PSG recordings average amounts of NREM and REM sleep in EPM1 patients were as follows: N1 8.1%, N2 55.4%, N3 27.7% and REM 8.8%. Earlier disease onset and more severe myoclonus correlated with decreased REM sleep proportion (r2 0.569, p=0.009 and r2 -0.616, p=0.006, respectively). The morphology of observed EDs differed in wakefulness and NREM-sleep compared to REM sleep. Specifically, spikes and polyspikes over central and vertex regions were observed in REM sleep, while no such morphology EDs was seen during wakefulness or NREM-sleep. The number of sleep epochs having EDs was associated with earlier EPM1 disease onset (r2 -0.491, p=0.033), but not with the disease duration (r2 0.190, p=0.436). However, the number of epochs with EDs was not associated with myoclonus severity. In ambulatory EEG-recordings myoclonic jerks were seen both with and without association with EDs.Conclusions:
EDs are common in wakefulness and sleep of EPM1 patients, but they do not seem to correlate with the disease severity. Compared to previous reports we did not find a decrease in EDs associated with disease duration. The spikes and polyspikes over central and vertex regions were specific for REM sleep in EPM1 patients. Considering a general assumption that EDs markedly decrease or disappear during REM sleep in other types of focal and generalized epilepsies, the presence of EDs in REM sleep in EPM1 warrants further studies to explore its role as potential diagnostic marker or as a disease specific biomarker associated with abnormal cortical excitability.Funding:
Academy of Finland, Business Finland grants, Kuopio University Hospital State Research Funding.