Neuropsychiatric symptomatology predicts seizure recurrence in newly treated patients
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Abstract
Objectives: To test the hypothesis that neuropsychiatric symptomatology is predictive of the success of seizure control in patients newly treated with antiepileptic drugs (AEDs), and that this predictive value adds to that provided by other clinical, imaging, and genomic factors in a multivariate model.
Methods: One hundred seventy newly treated patients with epilepsy completed the A-B Neuropsychological Assessment Scale (ABNAS) before commencing AED therapy and were prospectively followed up for 12 months. Patients were classified as nonresponsive if they had at least 1 seizure not explained by medication noncompliance or other significant provoking factors.
Results: Of the 138 patients in whom a drug response phenotype at 12 months was able to be determined, nonresponsive patients (n = 45) had a higher pretreatment ABNAS score than patients whose seizures were controlled (n = 93) (p = 0.007). A lesion on MRI was also associated with a higher risk of seizure recurrence (p = 0.003). On multivariate logistic regression, the ABNAS score, the MRI results, and a genomic classifier were all independently predictive of treatment outcome. For AED pharmacoresponse, this multivariate model had diagnostic values of 91% sensitivity, 64% specificity, 84% positive predictive, and 78% negative predictive values. The predictive value of the ABNAS score was validated in a second prospective cohort of 74 newly treated patients with epilepsy (p = 0.005).
Conclusions: The ABNAS provides prognostic information regarding successful seizure control in patients newly treated with AEDs. Furthermore, these results demonstrate the multifactorial nature of the determinants of AED response, with neuropsychological, structural, and genomic factors all contributing to the complex response phenotype.
Footnotes
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Supplemental data at www.neurology.org
Study funding: Supported by the NHMRC (400088 and 566843 to T.J.O., M.S., and N.J.), RMH Home Lottery Research Fund of Melbourne Health (chief investigator S.P.), Pfizer Inc and the Victor Hurley (chief investigator C.S.), and the Royal Melbourne Hospital Neuroscience Research Foundation (chief investigator T.J.O.). BioGrid Australia (formerly Bio21:MMIM) provided server space to house the databases, implemented an interface to facilitate data entry, and funded support staff to enter the data.
Disclosure: Author disclosures are provided at the end of the article.
Received September 10, 2009. Accepted in final form May 24, 2010.
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