Periodic EEG discharges and epileptic spasms involve cortico-striatal-thalamic loops on arterial spin labeling MRI

Abstract Periodic discharges are a rare peculiar EEG pattern, occasionally associated with motor or other clinical manifestations, usually observed in critically ill patients. Their underlying pathophysiology remains poorly understood. Epileptic spasms in clusters and periodic discharges with motor manifestations share similar EEG pattern and some etiologies of unfavorable prognosis such as Subacute Sclerosing Panencephalitis or herpes encephalitis. Arterial Spin Labeling Magnetic Resonance Imaging (ASL-MRI) identifies localizing ictal and inter-ictal changes in neurovascular coupling, therefore assumed able to reveal concerned cerebral structures. Here, we retrospectively analyzed ictal and inter-ictal ASL-MRI in patients aged 6m-15yrs (median 3y4m) with periodic discharges including epileptic spasms, and compared these findings to those of patients with drug-resistant focal epilepsy who never presented periodic discharges nor epileptic spasms as well as to those of age-matched healthy controls. Ictal EEG was recorded either simultaneously with ASL-MRI or during the close time lapse of patients’ periodic discharges, while inter-ictal exams were performed during the patients’ active epilepsy but without seizures during the ASL-MRI. Ictal ASL-MRI was acquired in five patients with periodic discharges (Subacute Sclerosing Panencephalitis (1), stroke-like events (3), West syndrome with cortical malformation (1), two of them also had inter-ictal ASL-MRI. Inter-ictal group included patients with drug-resistant epileptic spasms of various etiologies (14) and structural drug-resistant focal epilepsy (8). Cortex, striatum and thalamus were segmented and divided in 6 functional subregions: prefrontal, motor (rostral, caudal), parietal, occipital, temporal. Rest cerebral blood flow (CBF) values, absolute and relative to whole brain, were compared to those of age-matched controls for each subregion. Main findings were diffuse striatal as well as cortical motor CBF increase during ictal exams in generalized periodic discharges with motor manifestations (Subacute Sclerosing Panencephalitis) and focal CBF increase in corresponding cortical-striatal-thalamic subdivisions in lateralized periodic discharges with or without motor manifestations (stroke-like events and asymmetrical epileptic spasms) with straight topographical correlation with the EEG focus. For inter-ictal exams, patients with epileptic spasms disclosed CBF changes in corresponding cortical-striatal-thalamic subdivisions (absolute-CBF decrease and relative-CBF increase) more frequently when compared to the group of drug-resistant focal epilepsies, and not related to Vigabatrin treatment. Our results suggest that corresponding cortical-striatal-thalamic circuits are involved in periodic discharges with and without motor manifestations, including epileptic spasms, opening new insights in their pathophysiology and new therapeutical perspectives. Based on these findings we propose a model for the generation of periodic discharges and of epileptic spasms combining existing pathophysiological models of cortical-striatal-thalamic network dynamics.