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were more marked in patients with PGES but there was no evidence of a relationship with
central apnoea111. Early nursing interventions that reduced peri-ictal hypoxaemia were also
associated with shortening of PGES duration112. It remains controversial whether the
occurrence of PGES is associated with increased risk of SUDEP106,108.

SUDEP and epilepsy surgery

There is compelling evidence that patients with poorly controlled, predominantly generalised
tonic-clonic seizures are at greatest risk of SUDEP, and a seizure is frequently seen as the
terminal event. Intuitively therefore, good seizure control should translate into a reduced risk
of SUDEP. The mortality rates of 393 patients who underwent epilepsy surgery were
evaluated. The standardised mortality ratio (SMR) for patients with recurrent seizures post-
operatively was 4.69, with a SUDEP incidence of 7.5/1000 patient-years, whereas in patients
who became seizure free, there was no difference in mortality rate compared with an age-
and sex-matched population113. This compares with similar studies which, for example, found
a SMR of 1.8 in those with a good post-operative outcome versus 7.4 in those who failed
surgery114. Conversely, in a large, population-based epilepsy surgery cohort, there was no
association between mortality rates and seizure outcomes, although there was a clear
difference between patients who underwent surgery (SUDEP incidence 2.4/1000 patient-
years) and those who failed pre-surgical assessment (SUDEP incidence 6.3/1000 patient-
years)12. There has been recent interest in the tenet that there is a common factor predisposing
to surgical failure and an increased risk of SUDEP so that patients who respond poorly to
surgery also carry an increased risk of SUDEP and that, overall, surgery does not alter the
risk of SUDEP115. Proposed common factors include temporal lobe epilepsy which extends
beyond the temporal lobe into the insula, frontal orbital or frontal operculum region which
may favour ictal arrhythmias, central apnoea and secondary generalisation. This, in turn,
would increase the risk of SUDEP and the wide epileptogenic field would translate into a
poor post-operative seizure outcome115. Mortality studies performed in patients with vagal
nerve stimulators have shown that excess mortality associated with refractory epilepsy
reduced as a function of duration of use. The rate of SUDEP was 5.5/1000 patient-years in
the first 24 months and 1.7/1000 patient-years thereafter, possibly reflecting gradual increase
in efficacy over time. Stabilisation of measures of heart rate variability post-VNS
implantation116–118 have paralleled the improved mortality rates, although these findings are
not universal119,120.

Implications for management

Despite a wealth of studies reporting on proposed risk factors or mechanisms of SUDEP this
has not yet been translated into targeted therapeutic interventions and a reduced incidence of
SUDEP. In spite of this being a fundamental goal in the management of patients with
epilepsy, there has been a paucity of studies specifically addressing preventive or therapeutic
strategies.

Given the disturbance in cardiac autonomic control in patients with epilepsy, there has been
speculation as to whether cardiotropic medication, such as beta-antagonists, may have a
protective effect, although no studies have been performed in this regard69. Experimental
studies in rats with audiogenic seizures and ictal apnoea have shown that selective serotonin
reuptake inhibitors have a protective effect121, although relevant confirmatory clinical studies
are lacking. Of interest however, is the recent finding of neuropathological evidence of
involvement of the medullary serotonergic network in sudden infant death syndrome (SIDS)
cases with a significantly lower density of serotonin receptor binding sites, particularly in
male SIDS cases compared to controls122. Whether pharmacological modulation of the
brainstem serotonergic network or cardiac autonomic function results in a protective effect
remains to be seen.