Angular vestibulo ocular reflex loss with preserved saccular function in Machado-Joseph disease

Abstract

Objective: To provide a comprehensive evaluation of the vestibular function in Machado-Joseph Disease (MJD).

Methods: 21 MJD patients and 19 healthy Controls underwent a detailed clinical neuro-otological evaluation including VOR gain of all six semicircular canals by video Head Impulse Test (vHIT), remaining horizontal VOR function by Suppression Head Impulse test (SHIMP), and saccular function by cervical Vestibular Evoked Myogenic Potentials (cVEMP).

Results: All MJD had significantly lower VOR gain in all six semicircular canals (p < 0.001) with a mean ± SEM of horizontal gain of 0.52 ± 0.04 and vertical gain of 0.57 ± 0.03 versus Controls' gain of 0.95 ± 0.01 and 0.81 ± 0.02, respectively (p < 0.001). MJD showed also a significantly lower VOR gain on the SHIMP test with left gain of 0.51 ± 0.04 and right gain of 0.46 ± 0.03 versus Controls' gain of 0.79 ± 0.01 and 0.83 ± 0.03, respectively (p < 0.001). In contrast, MJD had normal saccular function reflected by the presence of cVEMP response in 18/20 patients and in 12/17 of Controls, with a non-significant difference between MJD and Controls of P13 and N23 peaks latency and normalized peak-to-peak amplitude. ROC analysis of horizontal VOR gain resulted in an area under the curve of 0.993 making the average lateral canals' VOR gain an excellent classifier of MJD vs Controls.

Conclusions: Horizontal and vertical VOR impairment with preserved sacculo-collic function seems to be a distinctive feature of MJD and could be explained by selective, mostly medial and superior vestibular nuclei degeneration. This study further supports the idea that horizontal VOR gain measured by vHIT could be a potential neurophysiological biomarker of MJD.

Keywords: Machado-Joseph disease; SHIMP; Spinocerebellar ataxia type 3; VOR; Vestibulo ocular reflex; cVEMP.