Abstracts

Rationale: To assess seizure control in patients with predominantly nocturnal epileptic seizures who were started on higher evening doses of antiepileptic drugs (AEDs). Methods: Patients with focal epilepsy from a tertiary care center with nocturnal or early morning seizures who had received a proportionally higher evening dose of AEDs were included in a retrospective review to assess efficacy and side effect profile of this dosing schedule as compared to median baseline seizure frequency over 12 months (Interquartile range (IQR) 6-30). Patients who had a ?50% reduction in seizure frequency (per month) were considered responders. Results: Seventeen subjects (9 males; median age 11.9 years (IQR) 8.8-14.6) had seizure onset at a median age of 7 years (IQR 2.5-8.1). Ten presented with a history of developmental delay. Etiologies included malformations of cortical development (n=3), tuberous sclerosis complex (n=1), anoxic encephalopathy (n=3); and was unknown in 10. Clinical presentation in 5 out of these 10 was consistent with a syndromic diagnosis of nocturnal frontal lobe epilepsy (NFLE) and in 3/10 with benign epilepsy with centrotemporal spikes (BECTS). The median number of previous AEDs was 2 (IQR 1-3) and the median number of current AEDs was 1 (IQR 1-2). The median initial seizure frequency per month was 12 (IQR 2.5-45) with a median duration of epilepsy of 6.3 years (IQR 2.6-9.4). After adjusting the nocturnal dose to be higher (median 66.6% of daily dose, range 39-100%) than the morning and/or afternoon ones, median seizure frequency per month was 0 (IQR 0-3) (p=0.001). Mean reduction of seizure frequency was 78.5% (SD 38.2%; median 100%, IQR 79.2-100%) and median time of follow-up after the modification was 3 months (IQR 2-7). Fifteen patients were classified as responders, 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions), and 4 (2 BECTS, 2 with lesions) with 75-90% of seizure reduction. Two were classified as non responders (both with unknown cause, including one who had failed epilepsy-surgery). Nine subjects (53%) received monotherapy after dose modification with OXC (4), LEV (4), or VPA (1) and in the remaining cases other AEDs (LTG, GBP, PHT, RUF, TGB, TPM) were combined in polytherapy with differential dosing; BID administration was used in 16 out of 17. None of the patients presented worsening of the seizures after dose modification. Two complained of transient side effects: fatigue (n=1) and somnolence (n=1). No meaningful interpretation could be obtained from trough drug levels in our small cohort with differential dosing. However, we feel that trough levels should be performed in the morning and evening to assess whether morning troughs would be higher as expected than evening which would be lower, because of the higher dose in the evening. Conclusions: Proportionally higher evening dose of AEDs in subjects with nocturnal seizures led to seizure freedom in 64.7%, and in 88.2% to ?50% seizure frequency reduction. Prospective studies need to be done in a larger cohort to validate our observation. Support: CAPES (Brazil).