Researchers at the Departments of Medicine, Psychiatry, Neurology and Paediatrics, University of Melbourne, Australia investigated the predictive value of neuropsychiatric symptomatology in control of seizures in patients with epilepsy newly treated with AEDs. The majority of the patients had localization related epilepsy. A neuropsychological assessment scale (ABNAS) was completed by 170 newly treated patients with epilepsy followed prospectively for 12 months. The ABNAS is a validated brief scale of cognitive and behavioral function that correlates with scales for memory, anxiety, and depression levels. A higher score, reflecting greater neuropsychiatric symptomatology and potentially more widespread brain dysfunction, is associated with AED unresponsiveness. Of 138 with a drug response phenotype at 12 months, 45 nonresponsive patients (at least 1 seizure) had a higher pretreatment ABNAS score than 93 whose seizures were controlled (p=0.007). Patients with a low pretreatment ABNAS score (<15) were more likely to be pharmacoresponsive at 12 months than those with a high ABNAS score (>15) (72/100 [72%] vs 21/38 [55%], p=0.049). A higher risk of seizure recurrence was also associated with a lesion on MRI (p=0.003). For a AED pharmacoresponse, a multivariate model (ABNAS, MRI, and genotype profile classifier) had diagnostic values of 91% sensitivity, 64% specificity, 84% positive predictive, and 78% negative predictive values. The predictive value of the ABNAS score was also validated in a second prospective cohort of 74 newly treated patients with epilepsy (p=0.005). [1]

COMMENT. A poor response to AEDs in newly diagnosed patients with epilepsy may be predicted by a high score on a pretreatment neuropsychological assessment scale, and MRI evidence of structural brain lesion and genomic factors also contribute to a multifactorial AED response phenotype. At least 30% to 40% of patients newly treated for seizures have further seizures despite appropriate AED therapy [2]. The above study, mainly in adults, mean age 39 years, demonstrates the importance of neuropsychological and genomic data in prediction of response of newly diagnosed epilepsy to AEDs. Neuropsychological testing and genomic typing are also assuming more prominent roles in the management of pediatric epilepsy. Of a total of 212 patients in the above study, 32 (15%) were children and adolescents, mean age 16, range 10-18 years, (per Dr Petrovski).

Partial epilepsy with antecedent febrile seizures plus (PEFS+). Genomic DNA from 4 patients with PEFS+ was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2. Two heterozygous de novo mutations of SCN1A were detected that caused loss of function of Navl.l, and were associated with seizure aggravation by AEDs. PEFS+ is similar to SMEI and GEFS+ clinically with sporadic onset and possible AED-induced seizure aggravation. Genotyping is helpful in the management of these epilepsies. [3]