Vigabatrin-associated brain MRI abnormalities in children: Associations with drug exposure and epilepsy etiology

To evaluate risk factors for vigabatrin-associated brain abnormalities on MRI (VABAM) in children, with emphasis on epilepsy etiology.

We conducted a retrospective cohort study using an institutional medical record database to identify children treated with vigabatrin between August 29, 2019, and August 18, 2025. Inclusion required at least two brain MRI examinations obtained before and during vigabatrin treatment. VABAM were defined as new MRI abnormalities developing during vigabatrin therapy that met prespecified imaging criteria. Clinical variables, including demographics, treatment exposure, and epilepsy etiology, were compared between patients with and without VABAM.

Sixty-four patients met the inclusion criteria, of whom 18 (28.1%) developed VABAM. Higher peak vigabatrin dose (OR 1.03, 95% CI 1.01-1.06) and concomitant prednisolone therapy (OR 4.07, 95% CI 1.22-17.3) were associated with VABAM in univariable analyses. In a multivariable model including treatment duration, higher peak vigabatrin dose remained independently associated with VABAM (OR 1.06, 95% CI 1.02-1.12); however, this association was attenuated after excluding treatment duration in a sensitivity analysis (OR 1.03, 95% CI 1.00-1.06). Genetic epilepsy was more frequent in the VABAM-positive group (9/18, 50.0%), whereas structural epilepsy predominated in the VABAM-negative group (34/46, 73.9%). Although the specific monogenic disorders differed between groups, variants involving GABA_A receptor subunit genes were identified in both.

Our findings support a potential relationship between vigabatrin exposure and VABAM while highlighting the sensitivity of this association to model specification. The differing etiologic and genetic profiles observed between patients with and without VABAM raise the possibility that underlying epilepsy etiology may also influence susceptibility. Given the small number of patients with individual genetic disorders, these findings should be considered hypothesis-generating and warrant validation in larger cohorts.