Sudden death in epilepsy: There is room for intracranial pressure.

Maxine Dibué,Marjolein Dremmen,Daniel Hänggi,Philippe Ryvlin,Jochem K H Spoor,Hans‐Jakob Steiger,Christiane Freiin Von Saß,Marcel A Kamp

doi:10.1002/brb3.1838

Maxine Dibué, Marjolein Dremmen + Show 6 more

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https://doi.org/10.1002/brb3.1838

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Abstract

IntroductionSudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy. One aspect not included in current models of SUDEP is the role of increased intracranial pressure (ICP) which can be observed immediately upon seizure activity in neurosurgical practice.MethodsWe conducted a systematic review of the occurrence of edema in patients with epilepsy reported to have died of sudden death who underwent brain autopsy or postmortem brain imaging and discuss how increased ICP may contribute to clinical features of SUDEP.Results19 eligible studies comprising a total of 623 patients were identified. Edema—mostly mild or moderate—was reported in 17% of cases and 74% of studies. 1% (n = 6) of the overall cases were clearly identified as having Dravet syndrome or an SCN1A mutation. In these patients, edema was found in 4 (67%) of cases.ConclusionEdema is regularly found in patients with epilepsy classified to have died from SUDEP. We argue that seizures preceding SUDEP may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to sudden death of patients with epilepsy. Furthermore, we hypothesize that mild edema may especially progress to severe edema in patients with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations.

Highlights

Sudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy
Isolated observations suggest that SCN1A patients may be at a higher risk for developing postictal edema due to dysregulation of sodium influx through mutated Nav1.1 channels into neurons and we wonder whether increased intracranial pressure (ICP) may generally represent one of the early pathomechanisms contributing to SUDEP in this patient group and potentially in others at higher risk (Büren et al, 2018; Le Gal, Korff, & Monso-Hinard, 2010; Myers, McMahon, & Mandelstam, 2017)
It is important to distinguish between SUDEP, which in the MORTEMUS study was shown to be a centrally induced postictal phenomenon with central apnea at the beginning of cardiorespiratory collapse and sudden cardiac death (SCD) which is the result of a diseased myocardium

Summary

| INTRODUCTION

Despite advances in understanding the pathophysiological events preceding sudden deaths in epilepsy patients and identification of certain risk factors, it remains an entity that has yet to be understood. A recent comprehensive overview summarizes risk factors and predictive biomarkers of SUDEP (Ryvlin, Rheims, & Lhatoo, 2019) and several authors have discussed potential mechanisms thereof during the recent 2 years (Allen, Harper, Lhatoo, Lemieux, & Diehl, 2019; Barot & Nei, 2019; Buchanan, 2019; DeGiorgio, Curtis, Hertling, & Moseley, 2019; Vilella et al, 2019) Insight into the likely multi-factorial mechanisms leading to SUDEP is of the utmost importance in the journey toward preventive and interventional strategies. In the recent comprehensive SUDEP review, the authors discuss our recently published case-report on a 21-year-old man with an SCN1A mutation who died 3 hr after a seizure due to transtentorial herniation, in which we discuss potential molecular mechanisms of sodium channel dysfunction promoting postictal cytotoxic edema. Isolated observations suggest that SCN1A patients may be at a higher risk for developing postictal edema due to dysregulation of sodium influx through mutated Nav1.1 channels into neurons and we wonder whether increased ICP may generally represent one of the early pathomechanisms contributing to SUDEP in this patient group and potentially in others at higher risk (Büren et al, 2018; Le Gal, Korff, & Monso-Hinard, 2010; Myers, McMahon, & Mandelstam, 2017)

| METHODS

Pollanen and SUDEP cases identified from March 2005 through

17 Renier and Autopsy of a 19-month-old boy with severe

| DISCUSSION

Findings

| CONCLUSION