PITTSBURGH — Children taking the anticonvulsant vigabatrin should have baseline and follow-up magnetic resonance imaging, because the drug has been associated with new-onset MRI hyperintensities in about 20% of those who take it, Dr. Phillip L. Pearl reported in a poster at the annual meeting of the Child Neurology Society.
Although the drug has never received Food and Drug Administration approval—because it can cause retinotoxicity with visual field constriction in about 30% of patients—some patients do receive it for compassionate use or in Institutional Review Board-approved protocols, Dr. Pearl said in an interview. U.S. patients usually obtain it from Canada. Vigabatrin is widely available outside the United States.
“Our results seem to support the original preclinical concerns about this drug,” said Dr. Pearl, a pediatric neurologist at the Children's National Medical Center, Washington.
The drug irreversibly inhibits gamma-aminobutyric acid transaminase. He described vigabatrin's effects on imaging in 15 patients (aged 11 months to 11 years) who underwent MRIs while taking it. Diagnoses included tuberous sclerosis complex (five patients), cortical dysplasia (five), cryptogenic infantile spasms (two), Down syndrome (one), metabolic encephalopathy (one), and mesial temporal sclerosis (one).
All of the patients had abnormal MRI scans during the course of vigabatrin therapy. However, three infants with normal baseline scans (two with cryptogenic infantile spasms and one with Down syndrome, all aged 12–13 months) experienced new-onset, vigabatrin-related T2 hyperintensities, Dr. Pearl said.
In one patient with infantile spasms, the abnormal signal occurred in the basal ganglia, thalami, anterior commissure, and brainstem. The second patient, who had Down syndrome, experienced the increased signal in the thalami, tectum, and corpus callosum. The signal occurred in the brainstem, palladi, and dentate nuclei of the third patient, who had infantile spasms. Diffusion-weighted imaging indicated intracellular cytotoxic edema in all three.
At the time of the abnormal scan, the mean dose of vigabatrin was 143 mg/kg per day, and the mean duration of therapy was just over 3 months. All of the abnormal signalling resolved when vigabatrin was discontinued. The abnormal scans in the other 12 patients were all related to their underlying diagnoses. The mean dose of vigabatrin at the time of their abnormal scan was 77 mg/kg per day, and the mean duration of therapy was 14 months.
Because the new-onset abnormalities appeared in very young patients, Dr. Pearl said, infants may represent a high-risk group and should be carefully followed by a neurologist. He said the abnormalities may be symptomatic, but he has not identified their clinical significance with certainty.
New-onset hyperintensities related to vigabatrin may be even more common, according to Dr. Pearl.
A scan of basal ganglia of a child on VGB shows signal abnormality.
The signal abnormality resolved once the child discontinued VGB therapy. Photos courtesy Dr. Phillip L. Pearl