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.
