Slow saccades in cerebellar disease

Abstract

Eye movements are frequently considered diagnostic markers indicating involvement of the cerebellum. Impaired amplitude of saccades (saccade dysmetria), impaired gaze holding function (horizontal or downbeat nystagmus), and interrupted (choppy) pursuit are typically considered hallmarks of cerebellar disorders. While saccade dysmetria is a frequently considered abnormality, the velocity of saccades are rarely considered part of the constellation of cerebellar involvement. Reduced saccade velocity, frequently called “slow saccades” are typically seen in a classic disorder of the midbrain called progressive supranuclear palsy. It is also traditionally diagnostic of spinocerebellar ataxia type 2. In addition to its common causes, the slowness of vertical saccades is not rare in cerebellar disorders. Frequently this phenomenology is seen in multisystem involvement that substantially involves the cerebellum. In this review we will first discuss the physiological basis and the biological need for high saccade velocities. In subsequent sections we will discuss disorders of cerebellum that are known to cause slowing of saccades. We will then discuss possible pathology and novel therapeutic strategies.

Atypical Phenotype in a Spinocerebellar Ataxia Type 2 Kindred

“…The cases in this cohort also had features typical of SCA2. For instance, all cases had significantly slow saccades which are known to strongly correlate with polyglutamine expansion, and can be present early in the stages of illness, even prior to the onset of other clinical features of SCA2 [ 10 ]. Owing to this, slow saccades are often considered to be highly significant and are a critical clue in the diagnosis of SCA2 [ 10 11 ].…”

“…For instance, all cases had significantly slow saccades which are known to strongly correlate with polyglutamine expansion, and can be present early in the stages of illness, even prior to the onset of other clinical features of SCA2 [ 10 ]. Owing to this, slow saccades are often considered to be highly significant and are a critical clue in the diagnosis of SCA2 [ 10 11 ]. Parkinsonism is a relatively common non-ataxic manifestation of SCA2, and patients with SCA2 related parkinsonism have been reported to carry low to intermediate range CAG repeats with CAA, CGG, and CGC interruptions [ 10 12 13 ].…”

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

“…Approximately 90% of SCA2 patients can have severe slowing of ocular movements and reduced saccade velocity associated with the impairment of excitatory burst neurons in the paramedian pontine reticular formation ( Jensen et al, 2019 ). A velocity reduction depends on the length of the CAG repeat expansions: the longer polyQ expansion, the greater velocity reduction ( Velázquez-Pérez et al, 2004 ; Velazquez Perez et al, 2007 ).…”

“…A summary of the ophthalmic manifestations of the polyQ autosomal dominant SCAs outlined in this review is provided in Table 1. Pula et al, 2011;Stricker et al, 2011;Lebranchu et al, 2013;Vaclavik et al, 2013;Nishiguchi et al, Pogacar et al, 1978;Rufa et al, 2002;Velazquez Perez et al, 2007;Geiner et al, 2008;Pula et al, 2011;Di Fabio et al, 2012;Jensen et al, Mariotti et al, 2007;Hübner et al, 2007;Rosini et al, 2020 SCA, spinocerebellar ataxia; RNFL, retinal nerve fiber layer; VOR, vestibulo-ocular reflex.…”

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

“…Eye movements are frequently impaired in SCA2; thus, reduced saccade velocity or "slow saccades" are observed in many SCA2 patients [105]. It was reported that the vestibuloocular reflex gain was reduced in 30% of SCA2 patients and the caloric responses were reduced in 75% of patients [106].…”