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.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
References: Bettencourt C, Lima M. Machado-Joseph disease: from first descriptions to new perspectives. Orphanet J Rare Dis. 2011;6(1):35. https://doi.org/10.1186/1750-1172-6-35 . (PMID: 10.1186/1750-1172-6-35216357853123549)
do Carmo Costa M. Recent therapeutic prospects for Machado-Joseph disease. Curr Opin Neurol. 2020;33(4):519–26. https://doi.org/10.1097/WCO.0000000000000832 . (PMID: 10.1097/WCO.0000000000000832)
Oliveira JBL, Martinez ARM, França MC Jr. Pharmacotherapy for the management of the symptoms of Machado-Joseph disease. Expert Opin Pharmacother. 2022;23(15):1687–94. https://doi.org/10.1080/14656566.2022.2135432 . (PMID: 10.1080/14656566.2022.213543236254604)
Furtado GV, Oliveira CM, Bolzan G, Saute JA, Saraiva-Pereira ML, Jardim LB. State biomarkers for Machado Joseph disease: validation, feasibility and responsiveness to change. Genet Mol Biol. 2019;42(1):238–51. https://doi.org/10.1590/1678-4685-gmb-2018-0103 . (PMID: 10.1590/1678-4685-gmb-2018-0103311889276687346)
Gordon CR, Joffe V, Vainstein G, Gadoth N. Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease). J Neurol Neurosurg Psychiatry. 2003;74(10):1403–6. https://doi.org/10.1136/jnnp.74.10.1403 . (PMID: 10.1136/jnnp.74.10.1403145708341757403)
Gordon CR, Caspi A, Levite R, Zivotofsky AZ. Mechanisms of vestibulo-ocular reflex (VOR) cancellation in spinocerebellar ataxia type 3 (SCA-3) and episodic ataxia type 2 (EA-2). In: Progress in Brain Research, vol. 171. Elsevier; 2008. p. 519–25. https://doi.org/10.1016/S0079-6123(08)00674-2 . (PMID: 10.1016/S0079-6123(08)00674-2)
Gordon CR, Zivotofsky AZ Caspi A. Impaired vestibulo-ocular reflex (VOR) in spinocerebellar ataxia type 3 (SCA3): bedside and search coil evaluation. J Vestib Res. 2014;24:351–5. https://doi.org/10.3233/VES-140527 .
Luis L, Costa J, Munoz E, et al. Vestibulo-ocular reflex dynamics with head-impulses discriminates spinocerebellar ataxias types 1, 2 and 3 and Friedreich ataxia. J Vestib Res. 2016;26(3):327–34. https://doi.org/10.3233/VES-160579 .
Zaltzman R, Sharony R, Klein C, Gordon CR. Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite subpopulation. J Neurol. 2016;263(11):2207–14. https://doi.org/10.1007/s00415-016-8251-8 . (PMID: 10.1007/s00415-016-8251-827502086)
Geisinger D, Elyoseph Z, Zaltzman R, Mintz M, Gordon CR. Angular vestibulo ocular reflex loss with preserved saccular function in Machado-Joseph disease. J Neurol Sci. 2021;424:117393. https://doi.org/10.1016/J.JNS.2021.117393 . (PMID: 10.1016/J.JNS.2021.11739333780779)
MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test: diagnostic accuracy in peripheral vestibulopathy. Neurology. 2009;73(14):1134–41. https://doi.org/10.1212/WNL.0b013e3181bacf85 . (PMID: 10.1212/WNL.0b013e3181bacf85198057302890997)
Schmitz-Hübsch T, Du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B. Scale for the assessment and rating of ataxia. Neurology. 2006;66(11):1717–20. https://doi.org/10.1212/01.WNL.0000219042.60538.92 . (PMID: 10.1212/01.WNL.0000219042.60538.9216769946)
Weyer A, Abele M, Schmitz-Hübsch T, et al. Reliability and validity of the scale for the assessment and rating of ataxia: a study in 64 ataxia patients. Mov Disord. 2007;22(11):1633–7. https://doi.org/10.1002/MDS.21544 . (PMID: 10.1002/MDS.2154417516493)
Maas R, Van Gaalen J, Klockgether T, Van de Warrenburg BPC. The preclinical stage of spinocerebellar ataxias. Neurology. 2015;85(1):96–103. https://doi.org/10.1212/WNL.0000000000001711 . (PMID: 10.1212/WNL.000000000000171126062625)
Guan Q, Zhang L, Hong W, et al. Video Head Impulse Test for early diagnosis of vestibular neuritis among acute vertigo. Can J Neurol Sci. 2017;44(5):556–61. https://doi.org/10.1017/cjn.2017.202 . (PMID: 10.1017/cjn.2017.20228862109)
Elsherif M, Eldeeb M. Video head impulse test in bilateral vestibulopathy. Brazilian J Otorhinolaryngol (English Ed. Published online). 2020;88:181–6. https://doi.org/10.1016/J.BJORL.2020.05.014 . (PMID: 10.1016/J.BJORL.2020.05.014)
Jardim LB, Hauser L, Kieling C, et al. Progression rate of neurological deficits in a 10-year cohort of SCA3 patients. Cerebellum. 2010;9(3):419–28. https://doi.org/10.1007/s12311-010-0179-4 . (PMID: 10.1007/s12311-010-0179-420467850)
de Oliveira CM, Leotti VB, Bolzan G, et al. Pre-ataxic changes of clinical scales and eye movement in Machado-Joseph disease: BIGPRO study. Mov Disord. 2021;36(4):985–94. (PMID: 10.1002/mds.2846633438269)
de Oliveira CM, Leotti VB, Cappelli AH, et al. Progression of clinical and eye movement markers in pre-ataxic carriers of Machado-Joseph disease. Mov Disord. 2022;38(1):26–34. https://doi.org/10.1002/mds.29226 . (PMID: 10.1002/mds.2922636129443)
Gittis AH, du Lac S. Intrinsic and synaptic plasticity in the vestibular system. Curr Opin Neurobiol. 2006;16(4):385–90. https://doi.org/10.1016/J.CONB.2006.06.012 . (PMID: 10.1016/J.CONB.2006.06.01216842990)
Ashizawa T, Figueroa KP, Perlman SL, et al. Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J Rare Dis. 2013;8(1):1–8. https://doi.org/10.1186/1750-1172-8-177 . (PMID: 10.1186/1750-1172-8-177)
Jacobi H, du Montcel ST, Bauer P, et al. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study. Lancet Neurol. 2015;14(11):1101–8. https://doi.org/10.1016/S1474-4422(15)00202-1 . (PMID: 10.1016/S1474-4422(15)00202-126377379)
Lin YC, Lee YC, Hsu TY, Liao YC, Soong BW. Comparable progression of spinocerebellar ataxias between Caucasians and Chinese. Park Relat Disord. 2019;62:156–62. https://doi.org/10.1016/j.parkreldis.2018.12.023 . (PMID: 10.1016/j.parkreldis.2018.12.023)
Leotti VB, de Vries JJ, Oliveira CM, de Mattos EP, Te Meerman GJ, Brunt ER, Kampinga HH, Jardim LB, Verbeek DS. CAG repeat size influences the progression rate of spinocerebellar ataxia type 3. Ann Neurol. 2021;89(1):66–73. https://doi.org/10.1002/ana.25919 . (PMID: 10.1002/ana.2591932978817)
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