Imaging biomarkers of sleep-related hypermotor epilepsy and sudden unexpected death in epilepsy: a review

• Published in: Seizure (London, England) Vol. 114; pp. 70 - 78
• Main Authors: Misirocchi, Francesco, Vaudano, Anna Elisabetta, Florindo, Irene, Zinno, Lucia, Zilioli, Alessandro, Mannini, Elisa, Parrino, Liborio, Mutti, Carlotta
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2024
• Subjects: Biomarker; Biomarkers; Death, Sudden - etiology; Epilepsy, Reflex; Humans; Imaging; Multicenter Studies as Topic; SHE; Sleep; Sudden Unexpected Death in Epilepsy; SUDEP; SHE; Biomarker; Sleep; SUDEP; Imaging
• ISSN: 1059-1311; 1532-2688; 1532-2688
• DOI: 10.1016/j.seizure.2023.12.001

•Imaging techniques are increasingly used to identify biomarkers in epilepsy, but their significance and optimal usage windows are currently not well established.•SHE biomarkers are merging from structural and functional/metabolic imaging, and comprehend both diagnostic, prognostic and susceptibility biomarkers.•Metabolic imaging biomarkers shed light on SHE pathophysiology, revealing an overactive cholinergic ascending pattern and an altered dopaminergic inhibition.•in SUDEP, imaging mainly targets risk/susceptibility biomarkers, with abnormalities found in autonomic, cardiorespiratory and arousal centers.•Most SHE and SUDEP biomarkers derived from small, single-center experiences and multicenter, longitudinal, well-designed studies are strongly encouraged. In recent years, imaging has emerged as a promising source of several intriguing biomarkers in epilepsy, due to the impressive growth of imaging technology, supported by methodological advances and integrations of post-processing techniques. Bearing in mind the mutually influencing connection between sleep and epilepsy, we focused on sleep-related hypermotor epilepsy (SHE) and sudden unexpected death in epilepsy (SUDEP), aiming to make order and clarify possible clinical utility of emerging multimodal imaging biomarkers of these two epilepsy-related entities commonly occurring during sleep. Regarding SHE, advanced structural techniques might soon emerge as a promising source of diagnostic and predictive biomarkers, tailoring a targeted therapeutic (surgical) approach for MRI-negative subjects. Functional and metabolic imaging may instead unveil SHE's extensive and night-related altered brain networks, providing insights into distinctions and similarities with non-epileptic sleep phenomena, such as parasomnias. SUDEP is considered a storm that strikes without warning signals, but objective subtle structural and functional alterations in autonomic, cardiorespiratory, and arousal centers are present in patients eventually experiencing SUDEP. These alterations could be seen both as susceptibility and diagnostic biomarkers of the underlying pathological ongoing loop ultimately ending in death. Finally, given that SHE and SUDEP are rare phenomena, most evidence on the topic is derived from small single-center experiences with scarcely comparable results, hampering the possibility of performing any meta-analytic approach. Multicenter, longitudinal, well-designed studies are strongly encouraged.