The interacting etiologies of hippocampal sclerosis in epilepsy: A scoping review

According to the International League Against Epilepsy classification, mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is considered an epilepsy syndrome. Several etiologies may precede HS, but there is little overview in the literature about these etiologies. We conducted a scoping review to systematically search, select, analyze, and synthesize the existing knowledge about the etiology of HS in patients with epilepsy. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were searched using a systematic search strategy. Relevant data were selected according to strict criteria. A bibliometric analysis was done by VOSviewer software. A total of 907 studies were selected and classified. The main classes of etiologies we found are prolonged (febrile) seizures, genetic predisposition, infection, autoimmunity, trauma, neurodegeneration, developmental aspects, toxins (e.g., domoic acid), and hypertensive events (e.g., Posterior reversible encephalopathy syndrome), with several interactions between different etiologies. Autoimmunity and neurodegeneration were the most recently described etiologies. We found that the etiology of MTLE-HS is complex, with several risk factors influencing susceptibility and a heterogenous pathophysiology between patients. Future, prospective studies addressing the interactions of these etiologies in the development of HS are warranted. A better understanding of the interacting etiologies of MTLE-HS could have a major impact on the development of more precise diagnostic biomarkers, preventive strategies, and treatment options for this epilepsy syndrome.