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symptomatic generalised epilepsy, temporal onset seizures, seizure lateralisation (right in
adults; left in children), seizure duration, contralateral electrographic seizure spread, AED
polytherapy and MRI-negative epilepsy100–102. In a patient experiencing a seizure with oxygen
desaturation, the probability of recurrence with subsequent seizures is 0.43100.

Neurogenic pulmonary oedema, which may in itself be insufficient to be fatal, has been
implicated in theories regarding respiratory dysfunction and SUDEP following a number of
postmortem reports and case studies7,20,89,96. In a sheep model of ictal sudden death, animals
that died had a greater increase in pulmonary vascular pressure and hypoventilation. When
airway obstruction was excluded by tracheostomy, central apnoea and hypoventilation were
observed in all, causing or contributing to death in two, whereas a third animal developed
heart failure with significant pathologic cardiac ischaemic changes88,104. The apparent
protective effect of supervision favours an important primary role for respiratory factors22, as
these can be influenced by relatively unskilled intervention, such as airway protection,
repositioning, or stimulation. It is unknown what proportion of SUDEP cases may be
prevented by such intervention.

Suppression of cerebral activity
The possibility of progressive suppression and eventually cessation of cerebral activity as a
cause of SUDEP, despite normal cardiac function, was introduced with the publication of a
case report of an intracranially monitored patient who died of SUDEP in which a seizure
started in one hemisphere and then spread to the other after several minutes. The EEG pattern
on the original side then changed to burst-suppression with spindling spike discharges,
followed by complete cessation of activity. The other hemisphere continued to show spike
discharges until ceasing suddenly a few seconds later. A pulse artefact on the EEG continued
for a further two minutes; there was no recording of respiratory activity. It was postulated
that the loss of EEG activity was not preceded by anoxia as both hemispheres were not
simultaneously affected105. Post-ictal generalised EEG suppression (PGES) occurs in up to
65% or more of adult patients with convulsive seizures106 and has been reported in monitored
SUDEP or near SUDEP cases107. It has been shown that >50 seconds of PGES significantly
increases the adjusted odds ratios for SUDEP and for each one-second increase in the duration
of PGES, the odds of SUDEP increases by a factor of 1.7%106. However, a small retrospective
study of 17 SUDEP cases and matched controls found no significant differences in either
presence or duration of PGES between the two groups108 and a clear link between PGES and
SUDEP continues to be elusive. A recent study evaluated sympathetic and parasympathetic
changes in seizure patients by measuring electrodermal activity and heart rate variability109.
An increase in electrodermal activity response amplitude and a decrease in parasympathetic-
modulated high-frequency power of heart rate variability were directly correlated to
prolonged PGES. It is possible that PGES may serve as a marker of post-ictal autonomic
dysregulation. The precise nature of the pathophysiological association is unclear. Excessive
post-ictal brainstem inhibition due to seizure-induced release of GABA and other neuro-
inhibitory peptides may contribute to death in some patients. This may be compounded by
antiepileptic medication36. This endogenous seizure-terminating mechanism could result in
blunting of the central hypoxic and hypercarbic respiratory drive, resulting in post-ictal
respiratory arrest, subsequent exacerbation of hypoxia, further cardiac destabilisation and
death due to hypoxia and secondary cardiac arrhythmia. This is consistent with the
observation that SUDEP occurs after a seizure, and could be a consequence of failed re-
establishment of respiration in the post-ictal phase. It has been shown that patients with PGES
are significantly more likely to be motionless in the post-ictal period and to have simple
resuscitative interventions performed (suction, oxygen administration, placed in recovery
position, vital signs checked)110. PGES in such individuals may indicate deeper post-ictal
coma, more delayed arousal and, at least hypothetically, a predisposition to SUDEP. One
study compared secondarily generalised convulsive seizures with and without PGES, and
found that oxygen desaturation duration and extent, as well as peak end-tidal CO2 elevation,