Abstracts

Zonisamide (ZNS) is FDA approved for treatment of focal seizures in adults and has been reported to be effective in treatment of seizures in children. We sought to determine the efficacy of ZNS after 12 months of treatment in children categorized by seizure type, cognitive status, concomitant anticonvulsants, and prior anticonvulsant use.
This is a retrospective study of 35 children (ages 8 months to 22 years, mean age 9 years) with intractable seizures treated with ZNS. Seizure frequency was calculated before and after 12 months of ZNS therapy. Charts were reviewed for seizure type (focal, generalized, mixed or infantile spasms), presence of cognitive impairment (no special education vs. special ed.), concomitant anticonvulsants (range: 0 to 5), and number of prior anticonvulsants (range: 1 to 12).
Of 35 patients, 5 (14%) were classified as having focal seizures, 13 (37%) had generalized seizures, 14 (40%) had mixed seizure types and 3 (9%) had infantile spasms. At 12 months 16 children were no longer taking ZNS due to lack of efficacy or side effects.
Good to excellent seizure control (50% - 100% reduction) was attained in 2 (40%) in patients with focal seizures, 7 (54%) with generalized seizures, 5 (36%) with mixed seizures, and 1 (33%) with infantile spasms.
Good to excellent control was achieved in 5 of 11 (45%) patients with no/mild cognitive impairment and in 10 of 22 (45%) with moderate/severe cognitive impairment. (No cognitive information on 2 children).
mong those children on ZNS and one other drug, 5 of 9 (56%) had excellent ([gt]90%) control and 2 of 9 (22%) had poor ([lt]50%) control. It is of note that only one in 5 in the excellent control group were on levetiracetam (LEV), whereas 2 of 2 in the poor control group were on LEV. (p = .0017). In contrast, 2 of 5 excellent responders wre on ZNS plus lamotrigine (LTG) and 0 of 2 poor responsders were on ZNS + LTG (p=.007).
Adverse effects (AEs) were not a function of dose, as children without AEs had a higher mean dose than those with AEs.
In this group of children, ZNS worked equally well on focal, generalized and mixed seizures. Efficacy of ZNS was independent of cognitive status. Adverse effects (AEs) were not a function of dose. This could be a function of different rates of metabolism (levels were not routinely obtained) or represent idiosyncratic responses to the medication.
Our finding that those children taking the combination of LEV and ZNS had a significantly worse outcome than those on LEV and a different drug, and that ZNS + LTG resulted in a better outcome than ZNS + other drugs warrants further study, both clinically and from the standpoint of mechanisms of action and/or pharmacokinetic interactions between these drugs.
[Supported by: UMDNJ Foundation Student Summer Fellowship for Marjorie Bunch]