Type, Etiology, and Duration of Epilepsy as Risk Factors for SUDEP: Further Analyses of a Population-Based...

We conducted a nationwide case-control study in Sweden to investigate the risk of sudden unexpected death in epilepsy (SUDEP) in relation to epilepsy duration, epilepsy type, and etiology in combination with occurrence and frequency of tonic-clonic seizures (TCS) and nocturnal TCS.

The study comprised 255 SUDEP cases and 1,148 epilepsy controls. Clinical information was obtained from medical records. The association between SUDEP and risk factors was estimated by odds ratios (ORs) with 95% CIs calculated by conditional logistic regression to account for matching by sex and calendar time.

The risk of SUDEP was elevated in people with focal (OR 1.48, 95% CI 1.00-2.20), generalized and focal (OR 3.51, 95% CI 1.55-7.96), or unknown (OR 2.43, 95% CI 1.29-4.57) vs generalized epilepsy type. Increased risk of SUDEP was also observed in relation to epilepsy with traumatic causes (OR 2.27, 95% CI 1.33-3.89 vs genetic etiology) or short duration (OR 1.71, 95% CI 1.01-2.87 for 0-5 vs 6-15 years duration). Among those with 1-3 TCS during the preceding year, structural epilepsy etiology was associated with a more than 10-fold increase 10.84 (4.85-24.27) in SUDEP risk compared with people with genetic epilepsy without TCS. The risk with ≥4 TCS the preceding year was similar among those with generalized and focal epilepsies. Those with ≥4 TCS had an OR of 210.73 (95% CI 28.40-∞) during years 0-5 compared with those free from TCS and an epilepsy duration of 6-15 years. The combination of short epilepsy duration (0-5 years) and nocturnal TCS conferred an OR of 45.99 (95% CI 12.19-173.61) compared with having longer duration (6-15 years) and being free from nocturnal TCS.

Although certain etiologies, such as post-traumatic epilepsy, seem to entail a higher SUDEP risk, our data indicate that frequent and nocturnal TCS carry a similar level of risk whether focal or generalized from onset. The tonic-clonic part of the seizure seems to be decisive for the fatal outcome. SUDEP risk associated with TCS is highest during the first years after the epilepsy diagnosis which calls for effective TCS treatment and vigilance from the onset of diagnosis.