Abstracts

Rationale: There is ongoing debate as to the possible superiority of ACTH over prednisolone in the treatment of epileptic spasms (infantile spasms). Although high dose ACTH (150 U/m2/d) appears to be superior in comparison to “traditional” dose prednisone or prednisolone (2 mg/kg/d), no trials have adequately compared high-dose ACTH to high-dose prednisolone (i.e. 4-8 mg/kg/d). As a follow-up to our previous study in a small cohort (Hussain et al 2014), we evaluated in a much larger cohort (1) the efficacy of high dose prednisolone for treatment of epileptic spasms, and (2) the efficacy of high-dose ACTH immediately following prednisolone failure. Methods: Since 2009, UCLA has adopted a standardized epileptic spasms hormonal treatment protocol as follows: All patients initially receive prednisolone (8 mg/kg/d [max 60 mg/d]; divided BID x 14 d). Patients who respond to prednisolone taper off over 14 days. Patients who do not respond to prednisolone immediately transition (without prednisolone taper) to natural ACTH (150 U/m2/d, divided BID x 14 d). In this retrospective study, we identified patients with video-EEG confirmed epileptic spasms who followed the protocol above. For each patient we tabulated relevant demographic and clinical parameters including age of onset, etiology, age at treatment, prior therapies, presence of hypsarrhythmia at baseline, presence/absence of video-EEG confirmed response (freedom from spasms and hypsarrhythmia) immediately following prednisolone and ACTH, and the presence and timing of epileptic spasms relapse. Results: We identified 102 consecutive children (41 female) with epileptic spasms who were treated with prednisolone at UCLA. Prior hormonal therapy (prednisolone and/or ACTH before care at UCLA) and prior vigabatrin failure was observed in 12 (12%) and 36 (35%) patients, respectively. Median age of epileptic spasms onset was 7 months (IQR 5, 12) and median latency from diagnosis to prednisolone initiation was 2.3 (0.5, 6.2) months. 60 (59%) patients had video-EEG confirmed response to prednisolone. Two patients exhibited a protocol violation and did start ACTH immediately after prednisolone failure. Among the remaining 40 prednisolone non-responders, 13 (33%) subsequently responded to ACTH. After prednisolone response, there were 16 (27%) relapses, and after ACTH response, there were 7 (54%) relapses. In considering only those patients without prior hormonal therapy exposure (n = 90), prednisolone response was substantially higher in VGB-naïve patients (70%) in comparison to patients with prior VGB failure (37%), with P = 0.004 (Chi-square). See Figure 1. Conclusions: Video-EEG confirmed response to very high dose prednisolone in this cohort was favorable and comparable to contemporary reports of efficacy for high dose prednisolone and ACTH. Response was especially high among children without prior hormonal therapy or vigabatrin. In settings in which access to ACTH is limited or cost-prohibitive, high-dose prednisolone before ACTH is a reasonable approach. A randomized controlled trial contrasting prednisolone and ACTH is warranted. Funding: This study was accomplished with support from the Elsie and Isaac Fogelman Endowment, the Hughes Family Foundation, and the UCLA Children’s Discovery and Innovation Institute.