Acute encephalopathy and brain abnormalities on magnetic resonance imaging during combination therapy with adrenocorticotropic hormone and vigabatrin for infantile spasms

Case presentation: A 11-month-old female patient with Trisomy 21 (Down Syndrome) who developed infantile spasms at 6-months-old. She was diagnosed with West Syndrome and first treated with Vigabatrin (VGB). A positive response was observed, with control of the spams and regression of hypsarrhythmia at the electroencephalogram register. She was well controlled until 10-months-old, when the spasms returned with developmental regression. A treatment with synthetic adrenocorticotropic hormone (ACTH) was started in a low dose, but with partial control of the spasms. It was decided to increase the dose of the ACTH and we observed regression of spasms and recovery of developmental milestones. An oral corticosteroid withdrawal was maintained. She evolved drowsiness, diarrhea, tachycardia, hypotension and abnormal movements, characterized by sudden limb movements (ballismus) and chorea on the face. A treatment for sepsis was initiated, with improvement in laboratory parameters and hypotension, but she persisted with encephalopathy, abnormal movements, paroxysmal tachycardia and diarrhea. A cranial tomography (CT) was performed, showing a symmetrical and bilateral image of hypoattenuation in the basal nuclei. All the clinical abnormalities stopped after withdrawing the VGB. Magnetic Resonance Imaging (MRI) findings showed T2/FLAIR hypersignal in basal nuclei with diffusion restriction.

Discussion: VGB, ACTH and prednisone are first-line treatments for IS. Benefits from the use of combination VGB and hormonal therapy are already established. Acute encephalopathy with extrapyramidal symptoms, dysautonomic features and vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) has been reported after the use of combination-therapy for IS. Asymptomatic VABAM is common and appears to be associated with the use of higher doses of VGB. Main locations for MRI abnormalities included globi pallidi, brainstem, followed by thalami and dentate nuclei. MRI abnormalities usually to be resolved following VGB discontinuation, in a mean interval of 3 months. A literature review supports increased risk of fulminant, symptomatic VABAM in patients receiving VGB in association with hormonal therapy. Patients with Trisomy 21 seem to be particularly sensible to evolve it.

Final comments: This report and review raise concerns regarding the safety of combination therapy with adrenocorticotropic hormone and Vigabatrin for Infantile Spasms, mainly in Trisomy 21 patients.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023