Eye Movement Abnormalities Are Ubiquitous in the Spinocerebellar Ataxias
Oculomotor abnormalities are common in the spinocerebellar ataxias (SCAs). In studies of SCAs 1, 2, 3, and 6, eye movement abnormalities correlate with disease severity. Oculomotor abnormalities may be the sole motor manifestation of early and/or premanifest disease; however, not all ataxia rating scales include oculomotor assessment. We sought to identify the prevalence and characteristics of oculomotor abnormalities at first presentation in a large SCA cohort, including those in earlier stages of disease. We performed a retrospective assessment of initial clinical examinations of SCA patients followed in the Massachusetts General Hospital Ataxia Unit and assessed with the Brief Ataxia Rating Scale (BARS). One hundred thirty-four SCA patients were assessed: 17 SCA1, 13 SCA2, 55 SCA3, 2 SCA5, 22 SCA6, 11 SCA7, 9 SCA8, and 5 SCA17, mainly in the early stages of disease (67.2% stage 0–1). Oculomotor abnormalities were present on initial assessment in 94.8%, including 7/9 stage 0 and 77/81 stage 1 patients. Stage 0/1 patients had frequent saccadic intrusions, nystagmus, and hypo/hypermetric saccades. Saccadic slowing was present even in early stage SCA7 and SCA2, eventually leading to ophthalmoplegia. The burden of oculomotor abnormalities correlated with disease stage, duration, and severity, remaining highly significant even when controlling for age. The ubiquitous presence of oculomotor abnormalities in the SCAs, particularly early in the course, underscores the importance of oculomotor assessment in ataxia rating scales such as BARS. These findings highlight the potential for quantitative physiological oculomotor measures as clinical biomarkers in natural history studies and clinical trials.
KeywordsClinical neurology examination Spinocerebellar ataxia Ocular motility, ocular physiological phenomena
Dr. Stephen completed the statistical analysis.
Study was not industry sponsored. It is supported in part by the National Ataxia Foundation and the MINDlink Foundation. This work was conducted with support from MGH Division of Clinical Research (DCR) Biostatistics Program and Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers.
Compliance with Ethical Standards
This study was approved by the Partners Institutional Review Board Human Studies Committee.
Conflict of Interest
The authors declare that they have no conflict of interest. There are no financial relationships deemed relevant to this manuscript for either author. Dr. Schmahmann receives consulting fees from Cadent pharmaceuticals and grant support from the National Ataxia Foundation and the Ataxia Telangiectasia Children’s Project. Dr. Schmahmann received financial support from Biohaven and Dr. Stephen received financial support from Biohaven, Sanofi/Genzyme, Bristol-Myers Squibb and Biogen for the conduct of clinical trials.