Abstracts

Rationale: Infantile spasms (IS) is a severe form of epileptic encephalopathy with significant impact on neurodevelopment. ACTH (Adrenocorticotropic hormone) and vigabatrin (VGB) are the treatments recommended by the American Academy of Neurology for this epilepsy syndrome. With either there is a relatively high recurrence rate. Novel data suggest potential benefit in the concomitant use of steroids and VGB in the treatment of IS. Here we report the effectiveness and safety of combination therapy with high-dose ACTH and VGB in 6 patients. Methods: A retrospective chart review was performed and patients retrieved who received simultaneous treatment with high-dose ACTH and VGB for IS. Data regarding age at spasm onset, etiology, time to treatment initiation, presence of developmental delay, prior treatments, clinical seizure response, electroencephalogram (EEG) findings and side effects were collected and analyzed. Results: Six patients (5 male and 1 female) with IS who were simultaneously treated with high-dose ACTH and VGB were identified. Age at the onset of spasms varied between 2 months to 3 years and 3 months.  EEG confirmed electroclinical spasms in all patients. Three had hypsarrhythmia and three had modified hypsarrhythmia on initial EEG. Five were classified as symptomatic (two with prematurity / perinatal intraventricular hemorrhage, and one each with hypoxic ischemic encephalopathy, 7q microdeletion, and unknown/presumed genetic) and one as cryptogenic. Two patients were already receiving other antiepileptic drugs (phenobarbital and levetiracetam) for focal seizures and two patients had undergone prior treatment for IS (valproic acid, levetiracetam, clonazepam). Time from IS onset to treatment initiation ranged from 5 days to 135 days (median 20 days). One of the patients received prior therapy with high-dose ACTH with resolution of IS but had recurrence 3 months later and at that point received dual therapy. The five symptomatic patients had developmental delay.  All patients received high-dose ACTH (150 IU/m² intramuscularly) followed by a 3 to 4 week wean and VGB (150 mg/kg/day) for 6 months. At 2 weeks after treatment initiation, all five symptomatic patients experienced resolution of both the clinical spasms and hypsarrhythmia. The patient  with cryptogenic spasms partially responded to treatment with resolution of clinical spasms, however the EEG showed modified hypsarrhythmia. At six months follow up, this patient had complete normalization of the EEG, no further spasms and normal development. Two patients with symptomatic IS had recurrence 1-3 months after the completion of dual treatment.  Four patients were still in remission at the last follow up visit. One child had hypokalemia and a viral upper respiratory tract infection while on high-dose ACTH that was successfully treated. Conclusions: Combination therapy with high-dose ACTH and VGB appears to be effective and safe for the treatment of infantile spasms, especially in symptomatic patients, which are often much more resistant to successful therapy with either agent when used individually. Funding: None