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

Aasef G. Shaikh, Sarah Marti, Alexander A. Tarnutzer, Antonella Palla, Thomas Owen Crawford, Dominik Straumann, John P Carey, Kimanh D. Nguyen, David Samuel Zee

Research output: Contribution to journalArticle

Abstract

Experimental animal models have suggested that the modulation of the amplitude and direction of vestibular reflexes are important functions of the vestibulocerebellum 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 vestibuloocular reflex (VOR) was measured by eye movement responses to changes in head rotation. The vestibulocollic reflex (VCR) was assessed with cervical vestibular-evoked myogenic potentials (cVEMPs), in which auditory clicks led to electromyographic activity 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 vestibulocerebellum probably underlie these deficits. This study offers insights into how the vestibulocerebellum 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.

Original languageEnglish (US)
Pages (from-to)3034-3041
Number of pages8
JournalJournal of Neurophysiology
Volume105
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Vestibulo-Ocular Reflex
Ataxia Telangiectasia
Reflex
Vestibular Evoked Myogenic Potentials
Head
Eye Movements
Cerebellar Diseases
Purkinje Cells
Dyskinesias
Motivation
Animal Models
Biomarkers
Muscles

Keywords

  • Ataxia telangiectasia mutated gene
  • Eye movement
  • Oscillopsia
  • Spatial orientation
  • Vestibulocollic reflex
  • Vestibuloocular reflex

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Ataxia telangiectasia : A "disease model" to understand the cerebellar control of vestibular reflexes. / Shaikh, Aasef G.; Marti, Sarah; Tarnutzer, Alexander A.; Palla, Antonella; Crawford, Thomas Owen; Straumann, Dominik; Carey, John P; Nguyen, Kimanh D.; Zee, David Samuel.

In: Journal of Neurophysiology, Vol. 105, No. 6, 06.2011, p. 3034-3041.

Research output: Contribution to journalArticle

Shaikh, Aasef G. ; Marti, Sarah ; Tarnutzer, Alexander A. ; Palla, Antonella ; Crawford, Thomas Owen ; Straumann, Dominik ; Carey, John P ; Nguyen, Kimanh D. ; Zee, David Samuel. / Ataxia telangiectasia : A "disease model" to understand the cerebellar control of vestibular reflexes. In: Journal of Neurophysiology. 2011 ; Vol. 105, No. 6. pp. 3034-3041.
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