Review: The past, present and future challenges in epilepsy‐related and sudden deaths and biobanking

Abstract

The past, present and future challenges in epilepsy-related and sudden deaths and biobanking Awareness and research on epilepsy-related deaths (ERD), in particular Sudden Unexpected Death in Epilepsy (SUDEP), have exponentially increased over the last two decades. Most publications have focused on guidelines that inform clinicians dealing with these deaths, educating patients, potential risk factors and mechanisms. There is a relative paucity of information available for pathologists who conduct these autopsies regarding appropriate post mortem practice and investigations. As we move from recognizing SUDEP as the most common form of ERD toward indepth investigations into its causes and prevention, health professionals involved with these autopsies and post mortem procedure must remain fully informed.Systematizing a more comprehensive and consistent practice of examining these cases will facilitate (i) more precise determination of cause of death, (ii) identification of SUDEP for improved epidemiological surveillance (the first step for an intervention study), and (iii) biobanking and cell-based research. This article reviews how pathologists and healthcare professionals have approached ERD, current practices, logistical problems and areas to improve and harmonize. The main neuropathology, cardiac and genetic findings in SUDEP are outlined, providing a framework for best practices, integration of clinical, pathological and molecular genetic investigations in SUDEP, and ultimately prevention.

Sudden unexpected death in epilepsy: The neuro-cardio-respiratory connection

“…Neurogenic pulmonary edema caused by generalized tonic-clonic seizures, especially of longer duration, could be a cause of SUDEP [11,14,52]. Postictal pulmonary edema is frequently (∼70%) present at autopsy in cases of SUDEP [18].…”

“…Furthermore, normal arousal mechanisms appear compromised in these patients. There are genetic epileptic syndromes that have a very high risk of SUDEP [14,15]. Mutations in sodium and potassium channel and other genes co-expressed in the brain and the heart have been shown to be responsible for such syndromes.…”

Hippocampal morphometry in sudden and unexpected death in epilepsy (SUDEP)

“…Dentate granule cell dispersion has been anecdotally recorded in 4% of SUDEP PM reports 12,22 , but not systematically evaluated through review of histology sections. In this current retrospective study, based on a similar archival review protocol to the published SIDS studies 8 , but incorporating quantitative rather than qualitative evaluation, GCL measurements did not reveal excessive dispersion or broadening in SUDEP.…”

“…MRI criteria include measures of hippocampal roundness and verticality, mesial positioning, subiculum thickness and depth or verticality of the collateral sulcus 15,16,24 . The main obstacle in the quantitative evaluation of HMAL in pathology sections is the lack of a vertical midline or adjacent sulcus as a reference 15,16 , macroscopic images of the brain being not available in all cases, particularly for coroners' sudden death investigations 12 . In PM cases, excessive folding of the CA1/subiculum is regarded as the most striking feature in HMAL 29 ; similar 'tectonic' hippocampal abnormalities are described in surgical hippocampal resections, with 'bulbous expansions' or convolutions in the subiculum/CA1 region, typically associated with corresponding invaginations of the dentate gyrus 27 .…”

“…In MRI studies in SUDEP, increased grey matter volume in the right hippocampus and parahippocampal gyrus (PHG), compared to healthy controls, was observed 11 . A systematic neuropathology analysis of hippocampal morphology in SUDEP series has not been carried out 12 . Our objective, in a large series of post-mortem (PM) cases from SUDEP and control groups, was to seek to identify a morphometric signature for SUDEP as a potential biomarker.…”