Abstracts

Rationale: To explore seizure outcomes and cognitive function in children with epilepsy treated with topiramateMethods: Open label, non-interventional multicenter trial(TOPMAT-EPP-401) in children age 6 - 16 with epilepsy and treatment with flexible dose TPM for 12 weeks. Kaufman-ABC, digit symbol test (HAWIK-3), verbal learning memory test (VLMT), tolerability, sick days, and CGI were recorded. Seizure frequency was compared to a 12 week retrospective baseline. The two sided asymptotic Mann-Whitney-U-Test was applied to test for between group differences and the two sided asymptotic Wilcoxon test to test for pre-post changes within samples (no corrections for multiple testing).Results: 54 patients (52% male; median age 11 yrs (range, 6-17) were documented. Mean duration of epilepsy was 32 months (SD +/- 40 months). 78% completed the study. Main reasons for discontinuation: AE(9%), insufficient efficacy (11%). 48% had a primary generalized, 43% with partial epilepsy. 72% used TPM in add-on therapy at beginning. 60% patients were on TPM monotherapy during the last 6 weeks in the study. At study end, maximum dose TPM was 3.5mg/kg/day (age 6-12) and 2.49mg/kg/day (>12). Seizure frequency (+/- SD) improved from 46.10 ± 112.82 to 28.78 ± 87.22 (p=0.003). 56% had >= 50% seizure reduction and 35% became seizure free. K-ABC, VLMT and digit symbol test was tested at baseline and endpoint. Following groups were defined: AED naïve patients with initial monotherapy who remained on monotherapy (group 1: n=14), patients converting from add-on to monotherapy (group 3: n=18), patient with a baseline AED remaining on add-on therapy (group 4: n=21). A single patient had initial TPM monotherapy and a second AED was added during the study (group 2: n=1). In pairwise comparisons between group 1, 3 and 4, there were no significant differences between groups as well as in the pre-post comparisons within groups on the Kaufman-ABC. VLMT test results showed neither significant within- group pre-post changes nor significant between group differences in the pre-post changes (p >0.05) beside of one spurious result in the perseveration error score in group 4. The digit symbol test did not reveal differences between the groups at first and last visit; however when comparing pre-post differences, group 1 scored significantly better than group 4, group 4 worsened(p<0.05). Number of sick days decreased from 2.49 ± 6.79 to 0.28 ± 0.98 during the last 12 weeks of the study (p<0.05). 33 AEs were at least possibly related to TPM. AE >= 5% were paresthesias (7% of patients), fatigue (7%), decreased appetite (6%), speech and language disorder (7%), and mental state problems NOS (6%). One patient was hospitalized due to vomiting with causal relationship to TPM.Conclusions: The findings suggest that topiramate is associated with a reduction in seizure frequency in children and adolescents with epilepsy. A high number of seizure free patients was achieved, number of sick days decreased significantly. In addition, there was no significant change in cognitive function as measured by VLMT and digit symbol test at the described doses.