Abstract
Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies.
Highlights
The incidence of sudden death is 20-fold higher in people with epilepsy than in the general population; sudden unexpected death in epilepsy (SUDEP) is the most common cause of premature death in people with chronic epilepsy
To elucidate which brain regions may be implicated in SUDEP, we investigated whether regional abnormalities in grey matter volume appear in those who had SUDEP, compared to healthy controls
Epilepsy groups were generally comparable for clinical parameters, except for factors included in the risk scoring, i.e. frequent convulsive seizures, nocturnal seizures, and onset of disease (Table 2)
Summary
The incidence of sudden death is 20-fold higher in people with epilepsy than in the general population; sudden unexpected death in epilepsy (SUDEP) is the most common cause of premature death in people with chronic epilepsy. Meta-analyses of SUDEP risk factors (Hesdorffer et al, 2011; Ryvlin et al, 2013a) have identified frequent convulsive seizures (53/year) as a major risk factor and several studies indicate that unsupervised nocturnal seizures significantly contribute to SUDEP risk (Lamberts et al, 2012). The Mortality in Epilepsy Monitoring Unit Study (MORTEMUS) reported a consistent pattern in video-EEG monitored SUDEP cases, of a convulsive seizure, followed by early and fatal cardiorespiratory dysfunction (Ryvlin et al, 2013b). Some studies support a primary respiratory cause with central apnoea, which has been related to postictal generalized EEG suppression, indicating profound depression of CNS functions (Lhatoo et al, 2010). Other studies report primary periictal cardiac arrhythmias and impaired heart rate variability accompanying SUDEP (Surges et al, 2010)
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