Comparison of anti-epileptic drug levels in different cases of sudden death

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George JR and Davis GG (1998) Comparison of anti-epileptic drug levels in different cases of sudden death. J Forensic Sci 43:3 598–603.

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Abstract: Sudden unexplained death syndrome (SUDS) in epilepsy is identified as death in an epileptic individual with no anatomic cause found at autopsy. SUDS appears to be associated with subtherapeutic levels of anticonvulsants. Sudden death with no demonstrable cause at autopsy accounts for 5% to 30% of deaths in epileptic individuals. In the majority of cases, however, the cause of death in epileptic individuals can be demonstrated at autopsy. We examined the anti-epileptic drug concentrations in decedents who died as a direct result of epilepsy and compared these findings with those from a control population of epileptic patients who died suddenly due to some unrelated cause. This retrospective study was conducted on all deaths involving patients with epilepsy examined at the Jefferson County Coroner/Medical Examiner office from 1986-95. Out of 115 total cases the underlying cause of death was epilepsy in 60 cases--52 cases of SUDS and 8 deaths caused by an accident precipitated by a seizure. In 44 cases death was unrelated to the decedent's epilepsy. In 11 cases the contribution of epilepsy to death could not be determined. Published articles on SUDS report subtherapeutic anti-epileptic medication levels in 63% to 94% of cases. We found subtherapeutic drug levels in 69% of the 52 cases of SUDS, in 75% of the 8 cases where a seizure precipitated an accident causing death, and in 34% of the control population. The incidence of subtherapeutic anticonvulsants is significantly greater in patients dying as a direct result of their epilepsy than in those dying of an unrelated cause.

Keywords: forensic science, epilepsy, seizure, sudden death, anticonvulsants, forensic pathology

Context

  • 10-year study of AED levels at autopsy in SUDEP cases compared with levels in epilepsy patients who died suddenly but not of SUDEP. Subtherapeutic AED levels were essentially twice as common in SUDEP cases as in controls. Kloster and Engelskjøn found subtherapeutic AED levels in 57% of SUDEP patients, with no data on rates for the control group, while Leestma et al. found subtherapeutic levels in 68% of cases. Opeskin et al. found from death records that 60% of SUDEP victims had subtherapeutic AED levels, although Opeskin et al. found no difference in the proportion of subtherapeutic levels among epilepsy patients who died of SUDEP versus those dying of other causes; in a in a similar study design Walczak et al. found no difference between SUDEP deaths and non-SUDEP deaths in epilepsy patients. In a metareview, in contrast, Téllez-Zenteno et al. found that in studies using non-SUDEP deaths as controls the most consistent risk factors were a seizure and subtherapeutic levels of AEDs. (See also Hughes.)

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