Page 372 - ILAE_Lectures_2015

Chapter 38

Sudden unexpected death in epilepsy

FERGUS J. RUGG-GUNN

Department of Clinical and Experimental Epilepsy, The National Hospital for Neurology
and Neurosurgery, Queen Square, London
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SUDEP is defined as the sudden, unexpected, witnessed or unwitnessed, non-traumatic, and
non-drowning death in patients with epilepsy with or without evidence for a seizure, and
excluding documented status epilepticus, in which postmortem examination does not reveal
a structural or toxicological cause for death1. Where autopsy is not performed, and for the
purpose of epidemiological studies, sudden death occurring in benign circumstances with no
known competing cause for death is classified as ‘probable SUDEP’. Despite an applicable
definition, and clear guidance where there is uncertainty, significant variability in use has
hampered efforts to integrate findings from multiple studies on epidemiological and risk
factor data and hence establish common relevant factors2,3.

Epidemiology

Sudden unexpected death in the general population is extremely rare in young adults with an
incidence of 5–10/100,000 person-years, while the rate climbs steeply with advancing age to
approximately 300/100,000 person-years in the elderly4. The incidence of sudden death in
patients with epilepsy is significantly higher and varies markedly with the population
studied5. For example, in population-based studies the incidence has been reported to be 0.35
and 2.7/1000 person-years depending on the methodologies employed6,7. This increases to
between 2 and 5.9/1000 person-years in cohorts of patients attending specialist epilepsy
clinics8-10, 3.4/1000 person-years in pupils with epilepsy enrolled in a special residential
school11 and up to 9.3/1000 person-years in epilepsy surgery candidates12,13. The incidence
of sudden death in young adults with intractable epilepsy is therefore many times that of the
general population, with a peak between the ages of 20 and 40 years14. In older age groups
the relative increased incidence of SUDEP is too small to measure, and is confounded by the
occurrence of co-morbidity such as cardiovascular, respiratory or cerebrovascular disease.

Risk factors

There is significant debate regarding risk factors for SUDEP. Relevant and independent risk
factors are difficult to establish given the non-independence of patient, syndrome, seizures
and treatment characteristics. Multiple logistic regression analyses require large cohorts of
patients to achieve statistical significance for each of the variables evaluated and this is
difficult to attain15. Furthermore, the high variability between studies in terms of patient
cohorts, definition, choice of control group, methodology and overall study quality precludes
not only a valid meta-analysis, but even a simple meaningful comparison.

Demographics
Descriptive studies have almost universally reported that patients with SUDEP are young
adults6,7,9,10,16-20. A number of biases exist however, including, by definition, the exclusion of
patients with significant co-morbidity associated with increasing age, such as ischaemic heart
disease or cerebrovascular disease, identified on postmortem examination9,16,20. Other
examples of bias include case identification through self-referral by bereaved relatives, most
commonly parents18, and studies with only small numbers of patients6,9. Case-control studies