Abstract
Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex.Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.
Highlights
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of premature death in people with epilepsy, and is second only to stroke as a neurological cause of years of life lost in the general population [1]
Given that our binary SUDEP risk score was based on FBTCS frequency threshold, we explored whether regional differences in 18FDG uptake were more directly related to convulsion frequency rather than our surrogate score for SUDEP risk
Whole-brain analysis demonstrated that high FBTCS burden— and high SUDEP risk—was associated with a large cluster of increased FDG uptake that included the right cerebellar deep nuclei, cerebellar vermis, pontine tegmentum, dorsal midbrain/periaqueductal gray (PAG), bilateral ventral diencephalon, bilateral thalamus, bilateral pallidum, left putamen, and left claustrum
Summary
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of premature death in people with epilepsy, and is second only to stroke as a neurological cause of years of life lost in the general population [1]. Patients with medically-refractory epilepsy and convulsive seizures are at high risk [2]. Sudden unexpected death in epilepsy is a tragic outcome in epilepsy, but sudden death remains sufficiently rare that it is difficult to conduct prospective mechanistic studies in this population. Several SUDEP risk factors have been identified, with frequent convulsive seizures, anti-seizure polytherapy, and increased duration of epilepsy emerging as the strongest predictors [7]. Two risk assessment inventories, the SUDEP-7 [8] and the International League Against Epilepsy (ILAE) combined analysis score [9], fail to distinguish between individuals dying with SUDEP and living patient controls with epilepsy. A recently validated probabilistic prediction score seems promising but is clinically-based and not designed to provide mechanistic insight [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
