Abstracts

Rationale: Recent data on treatment of infantile spasms suggest an overall response rate sustained at 3 months of 46% when using first line treatments (hormonal treatments and vigabatrin), unaffected by etiology (Knupp et al. Annals of Neurology 2016;79:475-484). Patients with pathogenic variants in the gene CDKL5 are often respond poorly to any treatment for infantile spasms, and epilepsy is often refractory. We aimed to evaluate response to these standard treatment regimens in patients with CDKL5 disorder-related spasms. Methods: Patients were recruited from three CDKL5 Centers of Excellence (Boston Children's Hospital, Children's Hospital Colorado, and Cleveland Clinic) with likely or known pathogenic variants in CDKL5 and epileptic spasms. We classified response to treatment as follows: full response (spasm free for >2 weeks), partial response (reduction in spasm frequency or transient spasm freedom < 2 weeks) or no response. Patients were excluded from analysis if there was inadequate data or if they did not receive at least one of the following first line medication for spasms: ACTH, oral corticosteroids or vigabatrin. Results: Spasms occurred in 77% (59/77) of patients with CDKL5 disorder. Of 18 patients included in this study, spasm onset occurred at median age 4 months (range 2 weeks to 36 months). Thirteen patients received ACTH, 2 with full response, 7 with partial response and 4 with no response. Three patients received prednisolone, 1 with full and 2 with partial response. Nine patients received vigabatrin, 1 with full response, 4 with partial response and 4 with no response or worsening. Of the 2 patients with full response to ACTH, one was treated sequentially with ACTH followed by prednisolone and the response was sustained at 10 months. The response in the other patient was not sustained (spasm free for only 1 month). The single patient with full response to vigabatrin, only after uptitrating levetiracetam, had sustained response for at least 5 years but had other seizures types. Overall, only 3/18 patients (17%) had a full response to first line treatments for epileptic spasms. Five other patients had full response to ketogenic diet (2) or other AEDs (3). Conclusions: Response of epileptic spasms to ACTH, oral corticosteroids and vigabatrin is low in patients with CDKL5 disorder (17%, 11% sustained at 3 months) compared to the reported response rate of 46% that was sustained at 3 months in a broader population of patients with infantile spasms. We propose a prospective controlled study that is adequately powered to systematically assess response to the first line treatments in CDKL5 disorder-related epileptic spasms. Alternate early treatment such as ketogenic diet may also be considered. Funding: International Foundation for CDKL5 Research, NINDS *Benke TA and Harini C are co-senior authors