Abstracts

Rationale: Many children with refractive epilepsy syndromes are found to have overlap with genetic conditions, and their epilepsy may overlap conditions such as Lennox-Gastaut Syndrome (LGS). Many patients have mixed seizure types, often having a generalized character with onset. Perampanel may offer a rational mechanism as add-on therapy for these patients with intractable epilepsy syndromes. Methods: Retrospective review (June2016-May 2017) of12 patients ( 8 male/ 4 female; average age 11 years {range 6-46 yrs}) with childhood onset LGS intractable or focal and generalized seizures were treated with perampanel after failing an average of 5 other treatments. Patients had 3 idiopathic causes, 2 had CNTNAP1, 2 had XP22.33 duplication, 1 GABR1/KMTD2, 1 trisomy 13, 2 hemimegencephaly, 1 KCNQ2, 1 GABR3A. Treatment with perampanel doses (1-8 mg ) was given as add-on therapy. Clinical response and seizure frequency were noted. Results: All patients had physical tolerance of the perampanel, but 4 had negative mood issues limiting treatment or dose escalation. Decreased seizures per month was seen in 10/12, with decreased tonic or generalized convulsions in the hemimegencephalic patients, the other genetic and idiopathic patients. Two with KCNQ2 or GABR3A showed no improvement and irritability limiting dose to 2mg daily. Most patients needed 2-4 mg daily, with one idiopathic patient having seizure freedom after adding perampanel to 5 other anticonvulsants. Conclusions: This clinical observation of 11 patients with add-on therapy with perampanel for intractable childhood epilepsy syndromes showed that the majority had improvement with low dose add-on therapy, and possible better response in the genetic groups not associated with the genetics of febrile epilepsy syndromes such as GABR3A and KCNQ2. More classification of genetic subtypes and potential response to perampamil may be warranted.