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Gaze holding deficits discriminate early from late onset cerebellar degeneration

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Abstract

The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.

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Acknowledgments

Dr. Tarnutzer and Dr. Bertolini were supported by the Swiss National Science Foundation, the Betty and David Koetser Foundation for Brain Research and the Zurich Center for Integrative Human Physiology, Switzerland. The authors thank Marco Penner for technical support.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Zurich, University of Zurich, Frauenklinikstr. 26, 8091, Zurich, Switzerland

    Alexander A. Tarnutzer, K. P. Weber, D. Straumann, S. Marti & G. Bertolini

  2. Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    K. P. Weber

  3. Medizinisch Radiologisches Institut, Zurich, Switzerland

    B. Schuknecht

Authors
  1. Alexander A. Tarnutzer
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  2. K. P. Weber
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  3. B. Schuknecht
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  4. D. Straumann
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  5. S. Marti
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  6. G. Bertolini
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Correspondence to Alexander A. Tarnutzer.

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Tarnutzer, A.A., Weber, K.P., Schuknecht, B. et al. Gaze holding deficits discriminate early from late onset cerebellar degeneration. J Neurol 262, 1837–1849 (2015). https://doi.org/10.1007/s00415-015-7773-9

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  • DOI: https://doi.org/10.1007/s00415-015-7773-9

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