Review: Neuropathology findings in autonomic brain regions in SUDEP and future research directions.

Autonomic dysfunction is implicated from clinical, neuroimaging and experimental studies in sudden and unexpected death in epilepsy (SUDEP). Neuropathological analysis in SUDEP series enable exploration of acquired, seizure-related cellular adaptations in autonomic and brainstem autonomic centres of relevance to dysfunction in the peri-ictal period. Alterations in SUDEP compared to control groups have been identified in the ventrolateral medulla, amygdala, hippocampus and central autonomic regions. These involve neuropeptidergic, serotonergic and adenosine systems, as well as specific regional astroglial and microglial populations, as potential neuronal modulators, orchestrating autonomic dysfunction. Future research studies need to extend to clinically and genetically characterized epilepsies, to explore if common or distinct pathways of autonomic dysfunction mediate SUDEP. The ultimate objective of SUDEP research is the identification of disease biomarkers for at risk patients, to improve post-mortem recognition and disease categorisation, but ultimately, for exposing potential treatment targets of pharmacologically modifiable and reversible cellular alterations.