Abstracts

Rationale: Vigabatrin treatment of infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities characterized by hyperintense T2 signals within deep brain structures (ie, basal ganglia, thalami, anterior commissure, corpus callosum, and midbrain). Reports suggested that these abnormalities occur in 10% to 30% of treated infants. We conducted a retrospective study to estimate the frequency of vigabatrin-associated MRI abnormalities in infants with IS. Methods: Medical records and 332 cranial MRIs, from 205 infants (aged ≤24 months at time of diagnosis) treated for IS with vigabatrin (vigabatrin-treated) or another antiepileptic therapy (vigabatrin-naïve), were retrospectively identified at 10 sites in the United States and Canada. The incidence and prevalence of prespecified MRI abnormalities were compared between the vigabatrin-treated and vigabatrin-naïve groups. Prespecified MRI abnormalities were defined as any hyperintensity on T2 or fluid-attenuated inversion-recovery sequences with or without diffusion restriction not readily explained by a radiographically well-characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. Results: The observed difference between vigabatrin-treated subjects versus vigabatrin-naïve subjects with respect to incidence of MRI abnormalities was statistically significant (36% versus 6%, respectively; P = .031), and the attributable risk was 30.1% (95% confidence interval [CI], 8.2% to 52%). Similarly, the estimated prevalence of prespecified MRI abnormalities was significantly higher among vigabatrin-treated versus vigabatrin-naïve subjects (22% versus 4%; P < .001), and the attributable risk was 13.6% (95% CI, 3.8% to 23.4%). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)—vigabatrin was discontinued in four. There also was evidence of a dose effect among subjects treated with vigabatrin (low dose [<125 mg/kg/day] versus high dose [≥125 mg/kg/day]), although this effect did not reach statistical significance. Moreover, the observed anatomic location of vigabatrin-associated MRI abnormalities (ie, the brainstem, cerebellum, basal ganglia, and thalamus) was consistent with that of previous reports in 13 of 17 vigabatrin-treated subjects (76.5%), although varying greatly in degree.