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

Maria Thereza Drumond Gama,Flávio Moura Rezende Filho,Orlando Graziani Povoas Barsottini,José Luiz Pedroso,Thiago Junqueira Ribeiro Rezende,Marcondes Cavalcante França Junior,Pedro Braga Neto

doi:10.1590/0004-282x-anp-2020-0386

Abstract

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. 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. 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. 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. 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.

Highlights

Spinocerebellar ataxia type 3 (SCA3) is an abnormal CAG repeat expansion of the ATXN3 gene, located on chromosome 14q1,2 and the most common autosomal dominant spinocerebellar ataxia worldwide
We demonstrated that nystagmus may be the first neurological sign in some patients with SCA3
The main questions discussed in this article are: Can patients with SCA3 in the first months of symptoms be misdiagnosed?; and should a genetic test for SCA3 be requested for a patient with positive family history and pure nystagmus as the first sign? the pathophysiological mechanisms related with pure nystagmus as the first sign indicate that flocculonodular lobe, its connections, or the vestibular system are the first structures to be damaged concerning the natural history of brain degeneration in patients with SCA3

Summary

Introduction

Spinocerebellar ataxia type 3 (SCA3) is an abnormal CAG repeat expansion of the ATXN3 gene, located on chromosome 14q1,2 and the most common autosomal dominant spinocerebellar ataxia worldwide. In the second or third decade of life, present with marked extrapyramidal features (parkinsonism and dystonia) and a more severe disease, while patients with adult onset usually present with cerebellar ataxia associated with pyramidal signs. Patients with early onset may present with pure cerebellar ataxia in the first years, and a severe parkinsonism and dystonia may occur in advanced stages[5]. 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

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