Vigabatrin‐associated reversible MRI signal changes in patients with infantile spasms

Abstract

SUMMARYPurpose: To evaluate the magnetic resonance imaging (MRI) of pediatric patients with infantile spasms (IS) treated with vigabatrin (VGB) in order to investigate whether VGB affects the brain. Methods: One hundred seven pediatric patients diagnosed with IS and treated with (n = 95) ‡120 mg/kg/day VGB or without (n = 12) VGB were included. MRI and diffusion-weighted imaging (DWI) were retrospectively analyzed. Results: Of the patients who had MRI scans during, but not before, VGB treatment (n = 81), 25 (30.9%) exhibited abnormal MRI signal intensity and/or restricted DWI in the deep gray nuclei and brainstem. Follow-up scans (performed in 15 of the 25 patients) revealed that these changes were reversible upon withdrawal of the medication. Analysis of patients undergoing scans before, during, and after VGB treatment (n = 14) revealed that four patients had abnormal MRI signal during treatment with VBG, two of whom reversed with cessation of VGB, one reversed without cessation of VGB, and another had persistent abnormal signal while being weaned from the VGB. Patients who had not received VGB treatment (n = 12) displayed normal imaging. Younger infants (£12 months) and those with cryptogenic IS were more likely to develop abnormal signal changes on MRI during VGB treatment. Discussion: In pediatric patients, VGB induces reversible MRI signal changes and reversible diffusion restriction in the globi pallidi, thalami, brainstem, and dentate nuclei. The risk for this phenomenon was greater in younger infants and patients with cryptogenic IS.

Abnormal Axial Diffusivity in the Deep Gray Nuclei and Dorsal Brain Stem in Infantile Spasm Treated with Vigabatrin

“…Previous studies have shown that children younger than 2 years of age were more likely to demonstrate abnormal signal intensity in the deep gray nuclei and dorsal brain stem compared with older children or adults when exposed to vigabatrin. 5,7,16 The observed abnormal signal intensity in the deep gray nuclei and dorsal brain stem in infants with relatively immature myelin exposed to vigabatrin may not be related to myelin vacuolationhence, the lack of significant alteration of D Ќ in the globi pallidi, thalami, and dorsal brain stem in our cohort of patients.…”

“…[5][6][7] The underlying microstructural changes responsible for the T2 and diffusion changes in the human brain are unknown. However, on the basis of animal studies, we postulated that the abnormal T2 signal intensity and diffusion restriction in the deep gray nuclei and dorsal brain stem were related to intramyelin edema.…”

“…[2][3][4] Recently, human studies have described reversible MR imaging abnormalities characterized by T2-weighted hyperintensities and/or restricted diffusion in the globi pallidi, thalami, dorsal pons, and midbrain in approximately 20%-30% of patients with infantile spasm. [5][6][7] Young age and high dose appeared to be risk factors for the development of these reversible changes in the deep gray nuclei and brain stem. [5][6][7] The underlying microstructural changes responsible for the T2 and diffusion changes in the human brain are unknown.…”

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…Hyperintensities in basal ganglia, thalamus, brainstem and dentate nucleus have, very recently, been shown in approximately one-third of those exposed to vigabatrin [76][77][78][79]. These MRI abnormalities may occur as early as 3 months after the initiation of therapy.…”

Electroretinogram Changes in a Pediatric Population With Epilepsy: Is Vigabatrin Acting Alone?

“…2 Further studies have described reversibility of MRI defect in infants. 10,11 In 1997, Eke et al reported 3 patients receiving a variety of antiepileptic drugs including vigabatrin showed symptomatic constriction of the visual field. 11 Electroretinogram abnormalities have been identified in these patients with visual field defined toxicity.…”