Rationale:
Epileptic spasm (ES) is an age specific seizure type that occurs usually between (b/w) 3 to 8 months of age, associated with stasis or regression of developmental milestones. Causes of ES include structural, genetic, metabolic, or cyptogenic/idiopathic. Standard FDA approved therapies are intramuscular-administered adrenocorticotropic hormone (ACTH), oral corticosteroids (OCS), and vigabatrin (VGB). Literatures comparing ACTH, OCS, and VGB make different conclusions regarding best initial therapy and preferred dose. Studies report low VGB response rate for treatment of ES (not due to tuberous sclerosis complex (TSC)), ranging from 27% to 39.4%.1,2,3,5
In addition, an evidence-based guideline on medical treatment (tx) of infantile spasms by the American Academy of Neurology in 2012 recommended the use of ACTH for short term treatment of children with ES (excluding those with TSC).4 This retrospective study assessed efficacy of VGB as a first-line treatment for ES (not due to TSC) at a tertiary referral center.
Method:
We performed a single-center, retrospective analysis of newly diagnosed cases of ES b/w January 2014 and June 2020. All patients underwent a comprehensive evaluation for ES, including brain MRI, metabolic and genetics consults. All patients were followed by a child neurologist or an epileptologist. Duration of follow-up was up to 1 year from tx initiation. Various clinical variables were collected (Table 1). Acquired structural etiology consisted of brain injury due to accidental and non-accidental trauma, in-utero stroke resulting in encephalomalacia. Innate structural etiology consisted of malformation of cortical development, agenesis of corpus callosum. Monitoring of vision was conducted by a pediatric ophthalmologist and included baseline assessment of visual acuity and visual field (VF) within 4 weeks of treatment initiation. While on therapy, these assessments were performed every 3-4 months. An electroretinogram (ERG) was performed at least once during duration of VGB treatment under anesthesia. After VGB was weaned off, assessments were continued for another 3-6 months. Resolution of ES with or without hypsarrhythmia was defined as sustained absence for 3 months after treatment initiation. Children were considered early responders if there was parental report of clinical remission at 2 weeks after treatment initiation, confirmed on video-EEG, with resolution of hypsarrhythmia, (if present). Late responders experienced clinical remission after 2 weeks of treatment, confirmed on video-EEG, with resolution of hypsarrhythmia, (if present).
Results:
Thirty-one patients were treated with VGB (Table 1). Sixteen (52%) of the 31 infants were either early or late responders (10 early and 6 late). All remained in remission at 12 months. Of the responders, 14/16 (87.5%) demonstrated no worsening of their development per neurologist’s serial follow up assessments. All 31 infants experienced no VF deficits related to VGB. Three out of seven patients who are currently taking VGB had prior cortical vision impairment (CVI) but showed no signs of retinal toxicity. Of the responders, 7/16 are currently taking VGB, while the remaining 9/16 have been completely weaned off VGB (median length of therapy 10.1 months). Amongst the patients who responded to VGB, early or late, 90% of the patients responded at a dose of 150-160 mg/kg/day. No patient had diagnosis of TSC. The non-responder and relapse groups consisted of 15/31 (48%).
Conclusion:
VGB appears to be as effective as ACTH as first-line therapy for ES across various etiologies (other than TSC). No patient in this study suffered clinically apparent VF deficit as a result of VGB. An effective dose where resolution of ES is seen appears to be 150-160mg/kg/day.
Funding:
:N/A
FIGURES
Figure 1