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Other organ pathology in SUDEP: There have been several studies addressing the presence of
associated or significant cardiac pathology in SUDEP which may relate to the cause of death.
Initial reports suggested increased heart weights and co-existing cardiac hypertrophy in some
patients with SUDEP18. In subsequent studies however, no difference in heart mass compared to
non-SUDEP controls was noted when corrected for body mass19,20. Extensive sampling of the
myocardium in SUDEP revealed frequent foci of reversible pathology (myocyte vacuolisation
and interstitial oedema) in addition to irreversible pathological changes (contraction band
necrosis, haemorrhage, fibrosis and hyper-eosinophilia of myocardial fibres) compared to control
groups. Regions of myocardial fibrosis have been described around vessels or interdigitating
between bundles of fibres20. In a further study, 13 blocks of myocardium were sampled from each
of 23 SUDEP cases and a significant increase in deep and subendocardial fibrosis was shown in
40% of the SUDEP patients compared to controls21. Cardiac fibrosis has not however been
reported in all post mortem SUDEP series18. The current Royal College of Pathologists guidelines
for autopsy practice in epilepsy deaths recommend that three blocks of left ventricle and one
block of right ventricle are sampled to exclude vascular-ischaemic damage or other cause of
cardiac death as myocarditis. This limited sampling may mean that smaller foci of cardiac fibrosis
are missed and more generous sampling protocols of up to 10 blocks per case, as in the
investigation of other sudden adult death cases22, may be a more cautious approach. Pulmonary
oedema has been reported in 5090% of SUDEP cases15,16,18. Lung weights in SUDEP cases did
not differ from non-SUDEP cases19 in another study. Toxicology screening is important in the
investigation of SUDEP, as in other adult sudden death cases, in order to exclude a toxic cause
of sudden death and for the monitoring of AED levels to assess compliance. This should include
blood, urine, and gastric contents for AEDs, drugs of abuse and alcohol level estimations.
Vitreous humour should be taken for biochemistry if diabetes or other metabolic disorder is
considered. Hair testing may also prove useful to test for long-term drug compliance if
indicated23. Molecular/genetic testing for channelopathies in SUDEP is likely to become more
routine24,25, for example SUDEP is more frequent in patients with Dravet syndrome and SCN1a
mutations26.

SUDEP: recognition, likely mechanisms and future directions: There are no neuropathological
diagnostic features of SUDEP but establishing this category allows such cases, which fit a pattern,
to be grouped together and identified. SUDEP can be further classified as ‘definite’ or ‘possible’
(cases where there is a competing cause of death at post mortem) or ‘probable’ where the autopsy
data is incomplete27. Epidemiological studies and current research to date support the notion that
SUDEP is an ictal event and that cardiac, pulmonary or autonomic dysfunction concurrent with
a seizure are the main mechanistic contenders. SUDEP is also likely to be multifactorial, with
different causal mechanisms contributing in each case. Recognition of SUDEP had been one of
the main obstacles prior to the 2002 National Sentinel Audit in the UK. Guidelines for best
practice in epilepsy deaths were subsequently issued by the Royal College of Pathologists. To
make progress in understanding what causes SUDEP, which is one step towards its prevention,
a ‘global action’ is required28, with team work between multidisciplinary professionals, including
neuropathologists.

SURGICAL NEUROPATHOLOGY AND FOCAL EPILEPSIES
Epilepsy surgery has been established as an effective treatment option in pharmacoresistant focal
epilepsies29,30. Following continued advances in imaging technology, structural lesions are
increasingly recognised in patients with chronic focal seizures. Electrophysiological evaluation,
for example surface or invasive EEG recordings, may further define the epileptogenic area prior
to tissue resection.