Structural imaging biomarkers of sudden unexpected death in epilepsy.
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.
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK.
Britta
B
Wandschneider
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK.
Matthias
M
Koepp
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK.
Catherine
C
Scott
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK.
Caroline
C
Micallef
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK 3 Neuroscience Department, Polytechnic University of Marche, Ancona, Italy.
Simona
S
Balestrini
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK 4 The Centre for SUDEP Research, National Institute of Neurological Disorders and Stroke, USA.
Sanjay M
SM
Sisodiya
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK 4 The Centre for SUDEP Research, National Institute of Neurological Disorders and Stroke, USA.
Maria
M
Thom
4 The Centre for SUDEP Research, National Institute of Neurological Disorders and Stroke, USA 1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK.
Ronald M
RM
Harper
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK 4 The Centre for SUDEP Research, National Institute of Neurological Disorders and Stroke, USA 5 Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Josemir W
JW
Sander
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK 6 Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands.
Sjoerd B
SB
Vos
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK.
John S
JS
Duncan
4 The Centre for SUDEP Research, National Institute of Neurological Disorders and Stroke, USA 7 Translational Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
Samden
S
Lhatoo
1 NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK 2 Epilepsy Society, Chalfont St Peter SL9 0RJ, UK 4 The Centre for SUDEP Research, National Institute of Neurological Disorders and Stroke, USA b.diehl@ucl.ac.uk.
Beate
B
Diehl
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D002648:Child; D003645:Death, Sudden / Q000209:etiology* / Q000473:pathology*; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D055815:Young Adult
autonomic; hippocampus; sudden death; sudep risk; voxel based morphometry