Sudden unexpected death in epilepsy: A search for risk factors

Hitiris N, Suratman S, Kelly K, Stephen LJ, Sills GJ, and Brodie MJ (2007) Sudden unexpected death in epilepsy: A search for risk factors. Epilepsy Behav 10:1 138–41.

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Abstract: Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Of the 6140 patients registered with the Epilepsy Unit at the Western Infirmary in Glasgow between 1982 and 2005, 529 had died, 62 (11.7%) of whom succumbed to SUDEP. All but 2 deaths occurred at home; 3 were witnessed. Two living controls were matched with each SUDEP case for year of birth, gender, and syndromic classification. Mean duration of epilepsy was significantly longer in cases compared with controls (P=0.001). More people succumbing to SUDEP had had a seizure within the previous year (P=0.007). There were no significant associations between SUDEP and a history of generalized tonic-clonic seizures, drug polytherapy, and current use of carbamazepine. There is an urgent need for a large-scale, prospective, international, community-based study of SUDEP to explore more closely the risk factors to plan preventive strategies.

Keywords: Antiepileptic drugs; Epilepsy; Risk factors; Seizures; Sudden unexpected death in epilepsy

Context

• Incidence study from Scotland. Over a 23-year period 11.7% of deaths among epilepsy patients were due to SUDEP. With retrospective matching of 2 controls for each case according to age, gender, and epilepsy syndrome, mean duration of epilepsy and seizure within the previous year correlated with increased risk of SUDEP, while polytherapy, history of generalized tonic-clonic seizures, and use of carbamazepine were not associated. Evidence for an association with polytherapy was found by Beran et al. and Nilsson et al. (see also Hughes). With regard to the increased risk of SUDEP in patents who experience GTCS, Timmings found that SUDEP victims are more likely to have idiopathic GTCS, Nashef et al. found a link with a history of GTCS, Opeskin et al. found a link with GTCS as the seizure type, Lhatoo et al. found increased risk of mortality for patients with this type of seizure, Walczak et al. in a prospective cohort study found increased risk of SUDEP in patients experiencing tonic-clonic seizures, Langan et al. found GTCS in the past 3 months increased the risk of SUDEP, and Surges et al. found that more GTCS per year increases the risk of mortality; Vlooswijk et al. on the other hand found no link with GTCS, as did this study. A potential link of CBZ with SUDEP was suggested by Timmings and Timmings, and evidence of CBZ’s impairment of autonomic function was provided by Persson et al. However Opeskin et al. and Vlooswijk et al. found no association, and Walczak concluded that the link is tenuous. The fact that mean duration of epilepsy was longer in cases than controls suggests some room for improvement in the study design, and also seemingly contradicts those studies where risk was highest in the initial years after diagnosis. 60 of 62 cases were fund at home and 59 of the 60 were in bed. 3 cases were witnessed, with seizure preceding death in each of these. Seizure in the last year was predictive, but seizure in the last 6 months or in the last 3 months was not predictive.