Homozygous CAG Repeat Expansion in Spinocerebellar Ataxia Type 6: Longitudinal Analysis of Vestibulo-Ocular Reflex Findings.

Abstract

Spinocerebellar ataxia type 6 (SCA6) homozygotes are known to have an earlier onset and faster disease progression than heterozygotes. Although several studies have reported more severe clinical manifestations in SCA6 homozygotes, longitudinal, quantitative assessments remain lacking. A 55-year-old female presented with intermittent positional dizziness/vertigo and gradually progressive gait disturbance. She denied a family history of similar symptoms. Neuro-ophthalmologic evaluations revealed spontaneous downbeat nystagmus, horizontal gaze-holding deficits and hypermetric saccades with preserved saccadic velocity. Bedside horizontal head impulses showed a perverted response. Video head impulse test (HIT) showed normal VOR gain in all six semicircular canals and bithermal caloric test was also normal. Brain magnetic resonance imaging (MRI) showed diffuse and prominent, pure cerebellar atrophy. Genetic testing for SCA using Sanger sequencing confirmed the expanded repeats for SCA6 with homozygous abnormal allele 20 repeats. During the 8-year follow-up, bedside HIT turned positive on both sides and accordingly decreased VOR gains with abnormal catch-up saccades in both horizontal canals (HCs) were detected during video HITs, while bithermal caloric test revealed canal paresis only on the right side. Follow-up brain MRI demonstrated more prominent diffuse cerebellar atrophy and indicated mild brainstem atrophy as well. Vestibular performance in SCA6 is characterized by frequent high-frequency angular VOR impairments, predominantly affecting the horizontal and posterior canals, while low-frequency responses remain variable. Neuro-otologic deterioration during follow-up in our patient may be partly attributed to involvement of the brainstem VOR pathway including the medial vestibular nuclei, in contrast to SCA6 heterozygotes who typically exhibit pure cerebellar involvement.