Bilateral Dentate Nuclei Hyperintensities and Response to 4-Aminopyridine in a Patient With Childhood-Onset GAA--Related Ataxia

Objectives: To report a novel imaging finding of bilateral dentate nuclei hyperintensities in a case of childhood-onset GAA--related ataxia (spinocerebellar ataxia 27B, SCA27B) and response to 4-aminopyridine (4-AP).

Methods: A 53-year-old woman with unsolved progressive cerebellar ataxia of childhood onset underwent clinical and imaging assessment and extensive genetic investigation.

Results: After excluding Friedreich ataxia, most common spinocerebellar ataxia-related expansions, and pathogenic variants in ataxia-related genes through exome sequencing, targeted long-range PCR and repeat-primed PCR analysis revealed a heterozygous pathogenic (GAA) expansion in Brain MRI showed bilateral dentate nuclei hyperintensities and peridentate white matter degeneration, a feature never reported before in SCA27B. Gait ataxia and frequency of falls improved after starting 4-AP.

Discussion: We confirm that SCA27B, initially considered a late-onset condition, can present with very early onset in childhood and describe a novel imaging feature of this common hereditary ataxia. Previous imaging studies had described a spectrum of findings, variably including cerebellar vermian and hemispheric atrophy, hyperintensities of the superior cerebellar peduncles, cerebral and brainstem atrophy, ventricular enlargement, and corpus callosum thinning. In this case, T2/FLAIR bilateral dentate nuclei hyperintensities and peridentate white matter degeneration expand the neuroradiologic spectrum associated with GAA--related ataxia of long duration.