Gaze holding deficits discriminate early from late onset cerebellar degeneration

Abstract

The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocityto-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.

Role of neural integrators in oculomotor systems: a systematic narrative literature review

“…; Tarnutzer et al. ). Thus, it is important to be aware of the vicinity of NI and characterize gaze‐holding ability to differentially diagnose a NI defect.…”

“…; Baier & Dieterich ; Kheradmand & Zee ; Patel & Zee ; Tarnutzer et al. ). In addition to the ocular signs, patients commonly are unable to coordinate movement and posture.…”

“…In spite of the flocculus being known to participate in vertical and horizontal gaze holding, there was no involvement of the flocculus in patients who have suffered strokes (Baier & Dieterich ) and neurodegenerative disorders that involved cerebellar atrophy (Tarnutzer et al. ) whom exhibited horizontal GEN. MRI scans of patients with GEN revealed cerebellar vermis, uvula, pyramid and tonsils affected. However, lesions to these structures are known to cause abnormal saccadic movement only (Glasauer ).…”

“…Cases reported have aetiologies such as infarctions and haemorrhages (Hommel & Bogousslavsky 1991;Halmagyi et al 1994;B€ uttner et al 2002;Helmchen et al 2002;Dieterich et al 2005;Rowe et al 2013;Kim et al 2014a), space-occupying lesions (Rett 2007;Karatas 2009;Lloyd et al 2009), syringobulbia (Weissman et al 1990;Nogu es et al 2010), Arnold-Chiari malformation (Weissman et al 1990;Wagner et al 2008;Ghasia et al 2014), demyelination (Averbuch-Heller et al 1995;Kim et al 2006Kim et al , 2014b, infection (Livorsi et al 2010), drug intoxications (Corbett et al 1989;Fischera et al 2009) and trauma (Sabates et al 1991;Van Stavern et al 2001;Kulkarni et al 2005;Odebode et al 2005). Additional investigations using imaging techniques such as CT or MRI scans have localized lesions within the brainstem and cerebellum, indicative of involvement of NI, including their abundant connecting structures which complete the gaze-holding system Helmchen et al 2002;Seo et al 2004;Dieterich et al 2005;Cho et al 2008;Nakamagoe et al 2012;Rowe et al 2013;Kim et al 2014a;Tarnutzer et al 2015). Thus, it is important to be aware of the vicinity of NI and characterize gaze-holding ability to differentially diagnose a NI defect.…”

“…Cerebellar lesions and defects in patients have been reported to show horizontal GEN and DBN (B€ uttner & Grundei 1995;Dieterich et al 2005;Wagner et al 2008;Karatas 2009;Lloyd et al 2009;Baier & Dieterich 2011;Kheradmand & Zee 2011;Patel & Zee 2014;Tarnutzer et al 2015). In addition to the ocular signs, patients commonly are unable to coordinate movement and posture.…”