And when I die … What time should I expect it?

Sudden death in epilepsy (SUDEP) is a common cause of among persons with (Ryvlin et al. 2013), although it occurs so rarely that clinical research has been principally limited to retrospective series, the available data depending on what signals or parameters were attended at time collection. Controlled studies large enrolments are still simply not feasible. Animal models and SUDEP have obvious potential for understanding disease mechanism rational interventions, variety animal variance their individual translational leaves many investigators skeptical about jumping therapeutic generalizations from experiments. On negative side ledger, far fewer than one-half highly cited upon counted, translate into human randomized trials (Vyas 2020). Single cell transcriptomics identify homologous cells mouse man may differ more they resemble each other (Hodge 2019). Furthermore, experiments intended simulate frequently do conditions manipulations occur cannot people (such as physical chemical methods seizure activity). positive genetic manipulation application myriad invasive non-invasive physiological recording imaging offer access systems ways possible past animals be foreseeable future humans continuous laryngoscopy during Fortunately, diverse genomic mutations, connectomic modifications experimental represent different optional paths converge singular mechanistic end-points, such balance excitation inhibition epileptogenesis obstructive apnea (Stewart Most importantly, linkages between datasets these convergence points can (and been) established defined successfully inform interventions. Because widely considered result events associated an seizure, neurological changes differences increase frequency intensity expected death. For example, tendency night relation sleep reported basis this day/night pattern explained. Sleep transitions (e.g. stage 2 REM) serve triggers thus probability seizures risk Alternatively, complex neuronal activity distinguish state waking alter within cortical regions its spread patterns through hypothalamic brainstem areas, ability given lethal derangements autonomic and/or respiratory function. In issue The Journal Physiology, Purnell (2021) use two convulsive significant seizure-associated mortality rates show (i) additional strong evidence relevance research; (ii) consistent function day; (iii) clear separation circadian rhythm determinant sudden variance. Importantly, make discussion point wake/sleep cycle reversed cycle, whereas serotonin level variations, one reversed. This squarely brain impacts cardiorespiratory impact seizure. What practical utility results by (2021)? First, help awareness expect person risks Increased often leads detailed focused collection and, addressing challenge mechanism, every drop precious. Does vary patient, apart control? answer yes. Is circadian-linked daytime day vs. final seizure? answers questions yet determined, but demonstrate will valuable. my opinion, work also opens door pharmacological interventions might ’flatten curve.’ Although eliminating altogether, mitigate reasonably reduce number cases. Doing without clinically disrupting endocrine good hold some keys separating predisposition, cause, coincidence effect, addition demonstrating Time tell. No competing interests declared. Sole author. funding was received.