title: Gaze holding deficits discriminate early from late onset cerebellar degeneration.
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.
authors.affiliation: Department of Neurology, University Hospital Zurich, University of Zurich, Frauenklinikstr. 26, 8091, Zurich, Switzerland, alalexander.tarnutzer@access.uzh.ch.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Tarnutzer
authors.forename: K P
authors.initials: KP
authors.lastname: Weber
authors.forename: B
authors.initials: B
authors.lastname: Schuknecht
authors.forename: D
authors.initials: D
authors.lastname: Straumann
authors.forename: S
authors.initials: S
authors.lastname: Marti
authors.forename: G
authors.initials: G
authors.lastname: Bertolini
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000473:pathology; D005133:Eye Movements / Q000502:physiology*; D005260:Female; D005403:Fixation, Ocular / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009759:Nystagmus, Pathologic / Q000209:etiology / Q000503:physiopathology*; D013132:Spinocerebellar Degenerations / Q000150:complications / Q000473:pathology / Q000503:physiopathology*