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Observational Study
. 2018 Dec:148:1-7.
doi: 10.1016/j.eplepsyres.2018.09.016. Epub 2018 Oct 2.

High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex

Shaun A Hussain  1 , Ernst Schmid  2 , Jurriaan M Peters  3 , Monisha Goyal  4 , E Martina Bebin  4 , Hope Northrup  5 , Mustafa Sahin  3 , Darcy A Krueger  6 , Joyce Y Wu  2 ; Tuberous Sclerosis Complex Autism Center of Excellence Network
Collaborators, Affiliations
Observational Study

High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex

Shaun A Hussain et al. Epilepsy Res. 2018 Dec.

Abstract

After initially successful treatment of infantile spasms, the long-term cumulative risk of relapse approaches 50%, and there is no established protocol to mitigate this risk. Although vigabatrin may be an effective means to prevent relapse, there is little guidance as to ideal duration and dosage. Using a cohort of children with infantile spasms and tuberous sclerosis complex (TSC), we evaluated the potential association of post-response VGB treatment and the rate of infantile spasms relapse. Patients with infantile spasms and clinical response to vigabatrin were identified among a multicenter prospective observational cohort of children with TSC. For each patient we recorded dates of infantile spasms onset, response to vigabatrin, relapse (if any), and quantified duration and dosage of vigabatrin after response. Time to relapse as a function of vigabatrin exposure was evaluated using survival analyses. We identified 50 children who responded to VGB. During a median follow-up of 16.6 months (IQR 10.3-22.9), 12 (24%) patients subsequently relapsed after a median of 7.8 months (IQR 3.1-9.6). Relapse occurred after VGB discontinuation in four patients, and during continued VGB treatment in the remaining eight cases. In survival analyses, risk of relapse was unaffected by the presence or absence of VGB treatment (HR 0.31, 95%CI 0.01-28.4, P = 0.61), but weighted-average dosage was associated with marked reduction in relapse risk: Each 50 mg/kg/d increment in dosage was associated with 61% reduction in risk (HR 0.39, 95%CI 0.17 - 0.90, P = 0.026). This study suggests that the risk of infantile spasms relapse in TSC may be reduced by high-dose vigabatrin treatment.

Keywords: Epileptic spasms; Secondary prevention; West syndrome.

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Conflict of interest statement

Disclosure of Conflicts of Interest

The remaining authors have no conflicts of interest. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

Figure 1:
Figure 1:. Formation of the nested study cohort
The analyses in the study are based on the 50 patients with infantile spasms who responded to VGB.
Figure 2:
Figure 2:. VGB exposure after IS resolution as a function of non-IS seizure burden
In the period following resolution of IS, VGB exposure was higher among patients with other (non-IS) continued seizures.
Figure 3:
Figure 3:. Time to IS relapse as a function of weighted-average VGB dosage
Kaplan-Meier plot of cumulative relapse as a function of weighted-average VGB dosage (Panel A) and peak VGB dosage (Panel B). P-value determined by Cox proportional hazards regression with single dichotomous risk-factor.
Figure 4:
Figure 4:. IS relapse as a function of weighted average and peak VGB dosage
IS relapse was least common among patients with high peak and weighted-average VGB dosage in the period following resolution of IS.
See this image and copyright information in PMC

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