The cerebellum's understated role and influences in the epilepsies

Approximately 1 in 26 people will develop epilepsy in their lifetime, but current treatment options leave as many as half of all epilepsy patients with uncontrolled seizures. In addition to the burden of the seizures themselves, chronic epilepsy can be associated with cognitive deficits, structural changes, and devastating negative outcomes such as sudden unexpected death in epilepsy (SUDEP). Thus, major challenges in epilepsy research surround the need to both develop new therapeutic targets for intervention as well as shed light on the mechanisms by which chronic epilepsy can lead to comorbidities and negative outcomes. Despite not being traditionally associated with epilepsy or seizures, the cerebellum has emerged as not only a brain region that can serve as an important target for seizure control, but one that may also be profoundly impacted by chronic epilepsy. Here, we discuss targeting the cerebellum for potential therapeutic intervention and discuss pathway insights gained from recent optogenetic studies. We then review observations of cerebellar alterations during seizures and in chronic epilepsy, as well as the potential for the cerebellum to be a seizure focus. Cerebellar alterations in epilepsy may be critical to patient outcomes, highlighting the need for a more comprehensive understanding and appreciation of the cerebellum in the epilepsies.