Abstracts

Rationale: Vigabatrin is the standard therapy for the treatment of infantile spasms (IS) secondary to tuberous sclerosis complex (TSC). Several studies have shown that vigabatrin is superior to hormonal therapy alone in this population. Combination therapy with oral steroids or adrenocorticotropic hormone (ACTH) with vigabatrin has shown faster resolution of infantile spasms but this has not been specifically studied in patients with tuberous sclerosis. Therefore we evaluated our cohort of patients with tuberous sclerosis presenting with infantile spasms to compare combination therapy versus vigabatrin monotherapy treatments.

Methods: Single center retrospective chart review and analysis of patients with tuberous sclerosis presenting with infantile spasms between 2014 and 2021. Data analyzed included the number of patients with single versus combination therapy, time to clinical spasms resolution, electroencephalographic resolution of hypsarrhythmia, recurrence of spasms and time to subsequent development of seizures.

Results: A total of 15 patients (N=15) with tuberous sclerosis were identified presenting with infantile spasms. Mean onset of spasms was around 8 months (range 4-14 months). 3/15 (20%) patients had focal seizures preceding onset of infantile spasms. 11/15 (73.33%) of patients were started on vigabatrin monotherapy for spasms treatment and 4/15 (26.66%) with ACTH and vigabatrin combination therapy. Mean time to spasm resolution in the monotherapy group was 10 days versus 3.5 days in the combination therapy group. All 4 patients in the combination group had documented resolution of hypsarrhythmia on EEG within 6 weeks of therapy and none (0/4) had recurrence of spasms. 2/11 patients who failed vigabatrin monotherapy were successfully treated with subsequent addition of ACTH. Spasm recurrence occurred in 2 patients on monotherapy and only 4/11 patients had documented resolution of hypsarrhythmia on EEG within the first 6 weeks of treatment initiation. Overall, only 2/15 patients remained seizure free after resolution of spasms. There was no difference in the average time to development of focal seizures following spasms resolution between monotherapy and combination therapy groups (6-12 months). No significant side effects were noted in either group. One patient had acute liver failure of unknown cause which led to discontinuation of vigabatrin and subsequent liver transplantation.

Conclusions: Vigabatrin monotherapy is the standard treatment for infantile spasms in patients with TSC. However our study demonstrates earlier resolution of both clinical spasms and hypsarrhythmia with combination therapy compared to vigabatrin alone as well as improved relapse rates in this group. Despite the small sample size, this finding is significant and larger studies will provide insight in the benefit of combination therapy for faster resolution of infantile spasms with sustained effect in patients with tuberous sclerosis.

Funding: Please list any funding that was received in support of this abstract.: none.