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are less conclusive. Some studies only included defined age groups and can draw no
conclusions regarding other age groups. Nevertheless, it is interesting to note that 7080%
of the studied population in a number of case-control studies were less than 45 years old14,21.
Data regarding age, however, is not available from a number of large studies due to age-
matching of control subjects14,21,22.

Of the remaining studies, the use of a cohort of non-SUDEP deaths as a control group may
bias the patient group towards a younger age due to exclusion of co-morbid conditions more
commonly associated with advancing age23-26, although young age as an independent risk
factor has not been universally reported27,28. The likelihood of selection bias is corroborated
by finding significantly less co-morbidity in the SUDEP group than the non-SUDEP group26.
In studies using living control subjects, younger age was not seen more frequently in the
SUDEP group, although numbers of SUDEP patients were small8.

Although a large number of descriptive studies have suggested that male gender is a
significant risk factor for SUDEP7,9,17,20,29, this has not been confirmed by the vast majority
of case-control studies21-23,26-28,24,30,34. In addition, a small number of both descriptive and
case-control studies have reported a significantly increased standardised mortality rate in
female patients, which may be attributable to a lower background rate of death in the female
non-SUDEP control group6,25.

Epilepsy characteristics
A number of case-control studies have suggested that early onset of epilepsy is a significant
risk factor for SUDEP21,24,26,27. For example, an eight-fold higher SUDEP risk in patients with
an onset of epilepsy between the ages of 0 and 15 years has been reported, when compared
to patients with seizure onset after 45 years of age21. However, while this may reflect a
different aetiological basis for the epilepsy, it may also merely be a surrogate marker for an
increased cumulative lifetime risk of having seizures for a longer period of time, as suggested
by other studies14,19,20. Conversely, there are several reports of a shorter duration of epilepsy
being associated with an increased risk of SUDEP although this is most likely as a result of
comparison with an older control population23,24,26. Furthermore, following conditional
multiple logistic regression analysis, a long duration of epilepsy (>30 years) was no longer a
risk factor after adjustment for seizure frequency28.

One would expect epilepsy syndrome to be a key factor in defining the risk of SUDEP. Yet
there is only limited evidence to support the association of epilepsy syndrome with an
increased risk of SUDEP21,27. Discordant results from the relatively few case-control studies
that assessed this risk factor and low numbers of patients in each group preclude detailed
evaluation or definitive conclusions25. In one study, 7 out of 57 (12%) SUDEP cases had
primarily generalised epilepsy compared to 12 out of 171 (7%) control subjects. Statistical
comparison revealed that there was a higher risk of SUDEP in patients with primary
generalised epilepsy compared to patients with focal, symptomatic epilepsy, although this
was only significant in men21. Nevertheless, although idiopathic primary generalised epilepsy
(IGE) is usually less refractory to treatment, individuals with IGE are well represented in
SUDEP cohorts. It is possible that specific epilepsy syndrome subtypes carry an increased
risk of sudden death due to phenotypic expression in other cerebral and possibly cardiac
structures.

Less controversy exists as to whether high seizure frequency is an independent risk factor for
SUDEP. Several descriptive and large case-control studies have reported an increased risk of
SUDEP in patients experiencing frequent seizures19,21,22,24,,28,29. This increased risk is most
marked for convulsive seizures6-8,18,19,22,28 rather than non-convulsive episodes, such as
complex partial seizures24. Moreover, on logistic regression analysis, it was noted that only
the frequency of convulsive seizures was relevant, and not the frequency of all seizures