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Horizontal Vestibulo-Ocular Reflex Deficit as a Biomarker for Clinical Disease Onset, Severity, and Progression of Machado-Joseph Disease

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Abstract

Because of the crucial importance of finding a useful biomarker for further clinical trials in Machado-Joseph disease (MJD), and based on our previous studies, we aimed to evaluate whether the horizontal vestibulo-ocular reflex (VOR) gain could be a reliable neurophysiological biomarker for the clinical onset, severity, and progression of the disease. Thirty-five MJD patients, 11 pre-symptomatic genetically confirmed MJD subjects, and 20 healthy controls underwent a detailed epidemiological and clinical neurological examination including the Scale for the Assessment and Rating of Ataxia (SARA). Their VOR gain was measured using the video Head Impulse Test system. Twenty of the MJD patients were re-tested after a period of 1–3 years. Horizontal VOR gain was abnormal in 92% of MJD, 54% pre-symptomatic, and 0% healthy controls. Horizontal VOR gain in the MJD group was significantly negatively correlated with SARA score in the first (r=0.66, p<0.001) and second (r=0.61, p<0.001) examinations. There was also a significant negative correlation between the percentage of change in horizontal VOR gain and the percentage of change in SARA score across both examinations (r=−0.54, p < 0.05). A regression model of the SARA score with the horizontal VOR gain and disease duration as predictors demonstrated that both the horizontal VOR gain and the disease duration had an independent contribution to the prediction of the SARA score. The horizontal VOR gain seems to be a reliable biomarker for the clinical onset, severity, and progression of MJD and could be used in further clinical studies.

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Availability of Data and Materials

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

The authors thank the patients and families that participated in the study.

Funding

This work was supported by the Israeli Chief Scientist Office, Ministry of Health (CSO MOH, IL) within the framework of the European-Latin America Consortium (EU-LAC) Health Joint Fund (grant # 3-000-14307). There is no further involvement of the funding body in this study.

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Authors and Affiliations

  1. School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel

    Zohar Elyoseph & Matti Mintz

  2. The Center for Psychobiological Research, Department of Psychology and Educational Counseling, Max Stern Yezreel Valley College, Yezreel Valley, Israel

    Zohar Elyoseph

  3. Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK

    Zohar Elyoseph

  4. Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Dario Geisinger & Carlos R. Gordon

  5. Department of Neurology, Meir Medical Center, Kfar Saba, Israel

    Roy Zaltzman & Carlos R. Gordon

  6. Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

    Matti Mintz & Carlos R. Gordon

Authors
  1. Zohar Elyoseph
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  2. Dario Geisinger
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  3. Roy Zaltzman
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  4. Matti Mintz
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  5. Carlos R. Gordon
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Contributions

Zohar Elyoseph: conception and design of the study, acquisition and analysis of data, drafting a significant portion of the manuscript and figures.

Dario Geisinger: conception and design of the study, acquisition and analysis of data, drafting a significant portion of the manuscript.

Roy Zaltzman: conception and design of the study, acquisition and analysis of data, drafting a significant portion of the manuscript.

Matti Mintz: conception and design of the study, drafting a significant portion of the manuscript.

Carlos R. Gordon: conception and design of the study, acquisition and analysis of data, drafting a significant portion of the manuscript and figures.

Corresponding author

Correspondence to Carlos R. Gordon.

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Ethical Approval

The protocol of the study was approved by the Ethics Committee (Institutional Review Board) of the Meir Medical Center, Kfar-Saba, Israel, and followed the tenets of the Declaration of Helsinki.

Competing Interests

The authors declare no competing interests.

Disclaimer

The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Zohar Elyoseph and Dario Geisinger contributed equally to the manuscript.

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Elyoseph, Z., Geisinger, D., Zaltzman, R. et al. Horizontal Vestibulo-Ocular Reflex Deficit as a Biomarker for Clinical Disease Onset, Severity, and Progression of Machado-Joseph Disease. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01552-2

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