Therapy in Sleep-Related Hypermotor Epilepsy (SHE)

The purpose of this review is to summarize and discuss current options and new advances in the treatment of sleep-related hypermotor epilepsy (SHE), focusing on pharmacological and surgical treatments.

Carbamazepine (CBZ) has traditionally been regarded as the first-line treatment option in SHE patients. In patients showing an unsatisfactory response to monotherapy, topiramate (TPM), lacosamide (LCM) and acetazolamide (ACZ) could be reasonable add-on strategies. The increasing understanding of the role of neuronal nicotinic acetylcholine receptor (nAChR) in SHE pathophysiology has led to the evaluation of compounds able to modulate this receptor system, including nicotine patches and fenofibrate. Despite polytherapy with two or more antiepileptic drugs (AEDs), about one-third of SHE patients suffer from drug-resistant seizures. In selected drug-resistant patients, epilepsy surgery is a therapeutic approach that offers high probability of recovery, with up to two-third of patients becoming seizure-free after resection of the epileptogenic zone. An evidence-based approach from randomized placebo-controlled trials in SHE patients is lacking, and current treatment recommendations are based only on case reports and small series. Furthermore, most of these case reports and case series involve patients with a known genetic defect, which only accounts for a small proportion of SHE patients. Therefore, a prospective study in a large cohort of sporadic SHE patients is necessary in order to provide clinicians with an evidence-based treatment for this rare form of epilepsy. An early and effective anti-epileptic treatment is mandatory for SHE patients, in order to prevent the risk of increasing seizure frequency throughout the disease course with relevant impact on patients' cognitive profile and daytime performances.