Abstracts

Rationale: Lacosamide (LCS) was FDA-approved as adjunctive therapy for adults with partial-onset seizures in 2009, but its safety and efficacy for pediatric use remains unknown. LCS can be given orally as chronic treatment, or intravenously for emergent treatment or oral-IV replacement therapy. Although approved only for partial epilepsy, in pre-clinical studies LCS displayed anticonvulsant efficacy in both generalized and partial epilepsy models. This study reviewed the pediatric outcomes of oral or IV LCS use for a broad range of seizure types.Methods: A retrospective chart review identified patients < 17 yo initiated on PO/IV LCS by our center: relevant clinical factors were collected. Outcome was determined by review of continuous EEG for inpatient emergent cases, otherwise seizure frequency was abstracted from the outpatient records. Mean seizure frequency (total and by seizure type) 3 mo before start and at last follow-up were calculated, and then the 50% responder rates were determined. Reason for discontinuation was classified as either due to lack of efficacy or adverse effects (AE's).Results: The analysis included 24 patients with mean seizure onset and LCS start of 3.4 yrs (0-10) and 9.8 yrs (2-17); epilepsy syndrome was partial for 19, generalized for 1, and uncertain/mixed for 4. Mean AEDs before LCS was 5.7. LCS was used as chronic PO therapy for 20 (1 was excluded from efficacy analysis due to unclear outcome): Four of 19 (21%) had > 50% total seizure reduction (responders) and 2 (11%) were seizure-free in the last mo of treatment. Mean treatment duration and mean dose was 6.4 mo and 7.4 mg/kg. Three of 15 (20%) with partial onset, 0 of 1 (0%) generalized onset, and 1 of 4 (25%) uncertain/mixed were responders. Ten (50%) were discontinued: 4 due to AE s. Mean dose by weight was not significantly different between responders and non-responders. Responders tended to be on a sodium channel blocker (SCB s) (p = .08) but not on levetiracetam (LEV) (p = .08): neither association was significant. IV LCS was used for 4 (mean age 6.75 yrs, range 3-11): 3 for status epilepticus (SE) and 1 as oral-IV replacement therapy. Mean IV loading dose was 112.5 mg (50-200 mg) corresponding to 4.44 mg/kg (.66 to 10 mg/kg); maximum therapy duration was 2 mo. No AE s due to IV LCS were reported. PO LCS was used once for non-convulsive status epilepticus (NCSE). Three of the 4 SE cases (75%) were eventually controlled; for 1 case, LCS was the last AED added.Conclusions: LCS appears to be safe for use as oral and intravenous therapy for pediatric epilepsy, even as oral-IV therapy for an extended interval. As adjunctive chronic oral therapy, responder rates were lower in comparison with adult studies (even after excluding seizure types other than partial): it cannot be determined if this is due to clinical or pharmacokinetic differences. In contrast to previous adult studies, combination therapy with a SCB and without LEV may be associated with better outcomes. For SE, adjunctive LCS was highly effective for the small number studied. Prospective randomized controlled trials are needed to confirm these findings.