White matter spongiosis with vigabatrin therapy for infantile spasms |
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| Authors: | Phillip L. Pearl Annapurna Poduri Sanjay P. Prabhu Chellamani Harini Richard Goldstein Richard M. Atkinson Hannah Kinney |
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| Affiliation: | 1. Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA;2. Robert's Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA;3. Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA;4. Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA;5. Office of the Medical Examiner, Boston, MA, USA;6. Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA |
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| Abstract: | The histopathology, “white matter spongiosis,” defined by electron microscopy (EM) as “intramyelinic edema,” has been associated with vigabatrin therapy in various animal models, but its role or significance in clinical studies is unknown. We conducted a neuropathological examination on a 27‐month‐old boy with bilateral polymicrogyria and epilepsy after sudden unexpected death in epilepsy (SUDEP). The patient was initiated on vigabatrin at 4 months of age, which controlled infantile spasms, and was continued as maintenance therapy. Autopsy showed a combination of developmental and acquired lesions: (1) bilateral gyral malformations of the frontal, parietal, temporal, and insular cortex; (2) agenesis of the olfactory tracts and bulbs; (3) hippocampal abnormalities: dentate gyrus bilamination and granule cell dispersion; and (4) areas of microscopic bilateral, symmetric white matter spongiosis in the brainstem central tegmental tract, amiculum and hilum of the inferior olive, medial longitudinal fasciculus, paragigantocellularis lateralis, optic nerves and chiasm, and hypothalamus. The white matter spongiosis was identical to the histopathologic lesions (which by EM exhibited intramyelinic edema) that were demonstrated in animal models on vigabatrin therapy, indicating that vigabatrin toxicity is not restricted to animal models. |
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| Keywords: | GABA transaminase inhibitors intramyelinic edema spongiform lesions SUDEP/sudden unexpected death in epilepsy vigabatrin toxicity |
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