Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS)
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REVIEW PAPER
Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS) Mathieu Dupré 1 & Ruben Hermann 2,3 & Caroline Froment Tilikete 1,3,4 Accepted: 13 September 2020 # The Author(s) 2020
Abstract The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) has emerged progressively during the last 30 years. It was first outlined by the neurootology/neurophysiology community in the vestibular areflexic patients, through the description of patients slowly developing late-onset cerebellar ataxia and bilateral vestibulopathy. The characteristic deficit of visuo-vestibulo-ocular reflex (VVOR) due to the impaired slow stabilizing eye movements was put forward and a specific disease subtending this syndrome was suggested. The association to a peripheral sensory axonal neuropathy was described later on, with neuropathological studies demonstrating that both sensory neuropathy and vestibular areflexia were diffuse ganglionopathy. Clinical and electrophysiological criteria of CANVAS were then proposed in 2016. Besides the classical triad, frequent chronic cough, signs of dysautonomia and neurogenic pains were frequently observed. From the beginning of published cohorts, sporadic as well as familial cases were reported, the last suggestive of an autosomal recessive mode of transmission. The genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. This pathological expansion was found in 100% of the familial form and 92% of sporadic ones when the triad was complete. But using the genetic criteria, the phenotype of CANVAS seems to expand, for exemple including patients with isolated neuronopathy. We propose here to review the clinical, electrophysiological, anatomical, genetic aspect of CANVAS in light of the recent discovery of the genetic aetiology, and discuss differential diagnosis, neuropathology and physiopathology. Keywords Neuronopathy . Ganglionopathy . Bilateral vestibulopathy . Head impulse test . Visuo-vestibulo-ocular reflex . RFC1
Introduction
Mathieu Dupré and Ruben Hermann contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-020-01192-w) contains supplementary material, which is available to authorized users. * Caroline Froment Tilikete [email protected] 1
Neuro-ophthalmology Unit, Hopital Neurologique et Neurochirurgical P Wertheimer, Hospices Civils de Lyon, Lyon, France
2
ENT, Cervico-Facial Surgery and Audiophonology, Hôpital Edouard Herriot, Hospices Civils de Lyon, F-69003 Lyon, France
3
Lyon Neuroscience Research Center, IMPACT Team, INSERM, U1028, CNRS, UMR5292, Lyon, France
4
Lyon I University, F-69373 Lyon, France
The association of vestibular dysfunction to chronic cerebellar ataxia has for long time been reported in patients with hereditary cerebellar ataxia, such as spinocerebellar ataxia type 3 (SCA3) [1], SCA1
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