Nystagmus may be the first neurological sign in early stages of spinocerebellar ataxia type 3

Abstract

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant spinocerebellar ataxia worldwide. Almost all patients with SCA3 exhibit nystagmus and/or saccades impairment. Objective: To investigate the presence of nystagmus as an early neurological manifestation, before ataxia, in some patients with SCA3 in the first six months of the disease. Methods: We evaluated a series of 155 patients with clinically and molecularly proven SCA3 between 2013 and 2020. Data regarding sex, age, age at onset, disease duration, CAG repeat expansion length, first symptom, presence of ataxia, scores on SARA and ICARS scales, and presence and characteristics of nystagmus were collected. Results: We identified seven patients with symptomatic SCA3 who presented with isolated nystagmus. In these seven individuals the age at onset ranged from 24 to 57 years, and disease duration from four to six months. Conclusions: Our study showed that nystagmus may be the first neurological sign in SCA3. This clinical observation reinforces the idea that the neurodegenerative process in SCA3 patients may start in vestibular system connections or in flocculonodular lobe. This study adds relevant information about pre-symptomatic features in SCA3 that may work as basis for a better understanding of brain degeneration and for future therapeutic clinical trials.

A comprehensive review of iPS cell line-based disease modelling of the polyglutamine spinocerebellar ataxias 2 and 3: a focus on the research outcomes

“…Ataxic dysarthria, the deficit in speech and swallowing caused by damage to cerebellar neural inputs 45 , has been the cornerstone of pre-symptomatic manifestation in patients with SCA2. Similarly, the recognition of nystagmus as a pre-symptomatic manifestation of the SCA3/MJD condition 46 further reinforces the importance of ophthalmologic examination.…”

Visual oculomotor abnormalities and vestibulo‑ocular reflex dynamics in polyglutamine spinocerebellar ataxias (Review)

“…Nystagmus has been described in both symptomatic (27,32,69) and pre-symptomatic carriers (12,15,69). Moreover, nystagmus can be the sole neurological sign of the early phase in clinical patients with SCA3 (70). A central oculomotor study has indicated that frequent SWJs during fixation and gaze holding, lower vertical smooth pursuit eye movement (SPEM) gain, decreased upward peak saccade velocity and increased total anti-saccadic error rate are common characteristics in pre-SCA3, while patients with ataxic SCA3 usually manifest as GEN, impaired horizontal SPEM and saccadic dysmetria (68).…”