Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 (n = 268), SCA6 (n = 117), other SCAs (n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia (n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression (n = 2; SCA2) or treatment response (n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores (n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification (n = 9), and imaging measures of atrophy (n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.

Balance Disorders and Ataxia Service Royal Victoria Eye and Ear Hospital East Melbourne Melbourne VIC 3002 Australia

Cantonal Hospital of Baden Baden Switzerland

Departamento de Medicina Interna Universidade Federal do Rio Grande do Sul Porto Alegre Brazil

Department of Clinical Neurophysiology Institute of Psychiatry and Neurology Warsaw Poland

Department of Genetics Neurogene National Reference Centre for Rare Diseases Pitié Salpêtrière University Hospital Assistance Publique Hôpitaux de Paris Paris France

Department of Neurology Centre of Hereditary Ataxias 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Neurology Massachusetts General Hospital Harvard Medical School Boston MA USA

Department of Neurology Medical School University of Pecs Pecs Hungary

Department of Neurosciences and Reproductive and Odontostomatological Sciences University of Naples Federico 2 Naples Italy

Department of Otology and Laryngology and Department of Neurology Harvard Medical School Boston MA USA

Faculty of Medicine University of Zurich Zurich Switzerland

German Center for Neurodegenerative Diseases University of Tübingen Tübingen Germany

Institut du Cerveau Paris Brain Institute ICM Inserm U1127 CNRS UMR7225 Sorbonne Université Paris France

NeuroMetrology Lab Nuffield Department of Clinical Neurosciences Medical Sciences Division University of Oxford Oxford OX3 9DU UK

Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK

Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Trust Oxford UK

Research Division Translational Genomics of Neurodegenerative Diseases Hertie Institute for Clinical Brain Research and Center of Neurology University of Tübingen Tübingen Germany

Roche Pharma Research and Early Development Neuroscience and Rare Diseases Roche Innovation Center Basel Basel Switzerland

Serviço de Genética Médica Centro de Pesquisa Clínica e Experimental Hospital de Clínicas de Porto Alegre Porto Alegre Brazil

The Florey Institute of Neuroscience and Mental Health Parkville Melbourne VIC 3052 Australia

University of California Los Angeles Los Angeles CA USA

Citace poskytuje Crossref.org