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Ataxia telangiectasia: a "disease model" to understand cerebellar control of vestibular reflexes


Shaikh, A G; Marti, S; Tarnutzer, A A; Palla, A; Crawford, T O; Straumann, D; Carey, J P; Nguyen, K; Zee, D S (2011). Ataxia telangiectasia: a "disease model" to understand cerebellar control of vestibular reflexes. Journal of Neurophysiology, 105(6):3034-3041.

Abstract

Experimental animal models suggest that modulation of the amplitude and direction of vestibular reflexes are important functions of the vestibulo-cerebellum and contribute to the control of gaze and balance. These critical vestibular functions have been infrequently quantified in human cerebellar disease. In 13 subjects with ataxia telangiectasia (A-T), a disease associated with profound cerebellar cortical degeneration, we found abnormalities of several key vestibular reflexes. The vestibulo-ocular reflex (VOR) was measured by eye-movement responses to changes in head rotation. The vestibulo-collic reflex (VCR) was assessed with cervical vestibular-evoked myogenic potentials (cVEMPs), in which auditory clicks lead to EMG activity of the of the sternocleidomastoid muscle. The VOR gain (eye velocity/head velocity) was increased in all subjects with A-T. An increase of the VCR, paralleling that of the VOR, was indirectly suggested by an increase in cVEMP amplitude. In A-T subjects, alignment of the axis of eye rotation was not with that of head rotation. Subjects with A-T thus manifested VOR cross-coupling; abnormal eye movements directed along axes orthogonal to that of head rotation. Degeneration of the Purkinje neurons in the vestibulo-cerebellum probably underlies these deficits. This study offers insights into how the vestibulo-cerebellum functions in healthy humans. It may also be of value to the design of treatment trials as a surrogate biomarker of cerebellar function that does not require controlling for motivation or occult changes in motor strategy on the part of experimental subjects.

Abstract

Experimental animal models suggest that modulation of the amplitude and direction of vestibular reflexes are important functions of the vestibulo-cerebellum and contribute to the control of gaze and balance. These critical vestibular functions have been infrequently quantified in human cerebellar disease. In 13 subjects with ataxia telangiectasia (A-T), a disease associated with profound cerebellar cortical degeneration, we found abnormalities of several key vestibular reflexes. The vestibulo-ocular reflex (VOR) was measured by eye-movement responses to changes in head rotation. The vestibulo-collic reflex (VCR) was assessed with cervical vestibular-evoked myogenic potentials (cVEMPs), in which auditory clicks lead to EMG activity of the of the sternocleidomastoid muscle. The VOR gain (eye velocity/head velocity) was increased in all subjects with A-T. An increase of the VCR, paralleling that of the VOR, was indirectly suggested by an increase in cVEMP amplitude. In A-T subjects, alignment of the axis of eye rotation was not with that of head rotation. Subjects with A-T thus manifested VOR cross-coupling; abnormal eye movements directed along axes orthogonal to that of head rotation. Degeneration of the Purkinje neurons in the vestibulo-cerebellum probably underlies these deficits. This study offers insights into how the vestibulo-cerebellum functions in healthy humans. It may also be of value to the design of treatment trials as a surrogate biomarker of cerebellar function that does not require controlling for motivation or occult changes in motor strategy on the part of experimental subjects.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > Neuroscience Center Zurich
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:26 May 2011 14:58
Last Modified:29 May 2017 22:52
Publisher:American Physiological Society
ISSN:0022-3077
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/jn.00721.2010
PubMed ID:21471399

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