Variability of antiepileptic medication taking behaviour in sudden unexplained death in epilepsy: Hair analysis at autopsy

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Williams J, Lawthom C, Dunstan FD, Dawson TP, Kerr MP, Wilson JF, and Smith PEM (2006) Variability of antiepileptic medication taking behaviour in sudden unexplained death in epilepsy: Hair analysis at autopsy. J Neurol Neurosurg Psychiatry 77:4 481–4.

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Abstract: BACKGROUND: Variable compliance with antiepileptic drugs (AEDs) is a potentially preventable cause of sudden unexplained death in epilepsy (SUDEP). Hair AED concentrations provide a retrospective insight into AED intake variability. METHODS: We compared hair AED concentration variability in patients with SUDEP (n = 16), non-SUDEP epilepsy related deaths (n = 9), epilepsy outpatients (n = 31), and epilepsy inpatients (n = 38). AED concentrations were measured in 1 cm hair segments using high performance liquid chromatography. Individual patient hair AED concentration profiles were corrected for "washout" using linear regression analysis. The coefficient of variation (CV) of the corrected mean hair AED concentration provided an index of variability of an individual's AED taking behaviour. Hair sample numbers varied between subjects, and so weighted regression estimates of the CV were derived for each group. RESULTS: The CV regression estimates for each group were: SUDEP 20.5% (standard error 1.9), non-SUDEP 15.0% (3.9), outpatients 9.6% (1.4), and inpatients 6.2% (2.7). The SUDEP group therefore showed greater hair AED concentration variability than either the outpatient or the inpatient groups (p<0.0001). CONCLUSION: Observed variability of hair AED concentrations, reflecting variable AED ingestion over time, is greater in patients dying from SUDEP than in either epilepsy outpatients or inpatients. SUDEP, at least in a proportion of cases, appears preventable.

Context

  • Variability of serum AED concentrations has been reported in a number of studies, but animal studies have indicated that postmortem measurements of serum levels can be unreliable (discussed in annotation at Hitiris et al.). This study used AED levels in hair from 4 groups of epilepsy patents taking AEDs: SUDEP victims, non-SUDEP deaths, living outpatients, and living inpatients. Using liquid chromatography, hair was analyzed in 1 cm segments. A linear correction for fading AED levels in hair over time was applied to data from each individual, though an exponential decay may better approximate the process. Coefficient of variation (CV) was lowest in the inpatient group, as expected given regular dosing, and was largest in the SUDEP group. Surprisingly, mean CV in the non-SUDEP deceased group was more than 50% larger than in the living outpatient group, a greater-than-expected difference unless AED non-adherence increases the likelihood of death even due to causes other than SUDEP. The CV in SUDEP victims was on average about twice that in outpatients living with epilepsy, supporting previous findings that low adherence to AED regimens may increase the risk of SUDEP.

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