CANVAS an update: Clinical presentation, investigation and management

Szmulewicz, David J.; McLean, Catriona; MacDougall, Hamish G.; Roberts, Leslie; Storey, Elsdon; Halmagyi, Michael

doi:10.3233/ves-140536

Cited by 83 publications

(110 citation statements)

References 41 publications

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“…The pathophysiology of CANVAS is not completely understood; however, this condition is reported as a ganglionopathy involving the sensory, vestibular, autonomic, facial, and trigeminal ganglia. 3,4 Previous pathological studies in CANVAS have demonstrated atrophy of the vestibular, facial, and trigeminal nerves and of the dorsal root ganglia. 1,4,11 The nonlengthdependent nature of sensory loss observed on neurophysiological testing in our cases supports a sensory ganglionopathy/neuronopathy rather than a classic length-dependent axonal sensory neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Previous pathological studies in CANVAS have demonstrated atrophy of the vestibular, facial, and trigeminal nerves and of the dorsal root ganglia. 1,4,11 The nonlengthdependent nature of sensory loss observed on neurophysiological testing in our cases supports a sensory ganglionopathy/neuronopathy rather than a classic length-dependent axonal sensory neuropathy. This is consistent with neurophysiological testing results in 14 CANVAS patients who were diagnosed with a sensory neuronopathy.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Sudomotor dysfunction is recognized in patients with CANVAS; however, the underlying pathophysiology has not been fully elucidated. 3,4 To describe novel histopathological features of this syndrome, we present 2 siblings who had CANVAS with unique findings of sweat gland denervation.…”

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confidence: 99%

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Sweat Gland Denervation in Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS)

Umeh

Polydefkis

Chaudhry

et al. 2016

Movement Disord Clin Pract

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Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a newly recognized disorder characterized by cerebellar ataxia, nonlength-dependent sensory impairment, and bilateral vestibular loss. Sudomotor dysfunction has been described in CANVAS; however, the underlying pathology is not well characterized. To describe novel histopathological features of this syndrome, 2 siblings are presented who had CANVAS with unique findings of sweat gland denervation. Skin biopsy testing was performed to assess sudomotor structure and revealed markedly reduced sweat gland nerve fiber density below the 2.5th percentile in both patients. These histopathological findings suggest that postganglionic sudomotor dysfunction is an additional feature of CANVAS.Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized disorder characterized by cerebellar ataxia, nonlength-dependent sensory impairment, and bilateral vestibular loss. 1,2 Sudomotor dysfunction is recognized in patients with CANVAS; however, the underlying pathophysiology has not been fully elucidated. 3,4 To describe novel histopathological features of this syndrome, we present 2 siblings who had CANVAS with unique findings of sweat gland denervation. Case Series Case 1A woman aged 63 years presented with a 12-year history of numbness in the lower extremities, a 10-year history of slowly progressive gait ataxia, and a 3-year history of dysarthria. She reported decreased sweating and chronic cough. She had a history of hypertension and seizures. Her examination was notable for spontaneous downbeat nystagmus, impaired vestibulo-ocular reflex on head impulse testing, dysarthria, moderate to severe appendicular dysmetria, and severe gait ataxia. Sensory examination revealed decreased pinprick sensation in the face and lower extremities. She had 3+ reflexes in the upper and lower extremities except for 1+ Achilles reflexes. Case 2The sibling of case 1, a man aged 60 years, presented with a 15-year history of slowly progressive gait ataxia and a 2-year history of dysarthria. He reported generalized lack of sweating and chronic cough. He had a history of bradycardia status post pacemaker placement. His examination showed gaze-evoked horizontal nystagmus, impaired vestibulo-ocular reflex on head impulse testing, dysarthria, moderate appendicular dysmetria, and markedly ataxic gait. On sensory examination, he had decreased pinprick sensation in the lower extremities. He had 3+ reflexes in the upper and lower extremities except for 2+ Achilles reflexes. ResultsLaboratory tests for several causes of ataxia, including vitamin deficiencies, infectious causes, and autoimmune causes, were

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sweat Gland Denervation in Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS)

Umeh

Polydefkis

Chaudhry

et al. 2016

Movement Disord Clin Pract

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“…The Romberg test on foam rubber has a sensitivity of up to 79% and a specificity of up to 80% for detecting both patients with unilateral and those with bilateral vestibular loss (Petersen et al, 2013, Fujimoto et al, 2009b. Although abnormalities in the other vestibular tests during physical examination can be found (Kheradmand & Zee 2012;Szmulewicz et al, 2014), this review will not focus on them, since the main challenges for diagnosing and quantifying BVH are not encountered in these tests, except for HIT and the test for DVA; they will be discussed separately below.…”

Section: Neuro-otological and Vestibular Physical Examinationmentioning

confidence: 99%

“…magnetic resonance imaging, computed tomography), lumbar puncture, sensory nerve action potentials, speech assessment, etc. (Zingler et al, 2008a(Zingler et al, , 2009Jen 2009;Szmulewicz et al, 2011Szmulewicz et al, , 2014Requena et al, 2014). However, these tests are mainly used for determination of coexisting problems or the etiology of BVH (Table 2.1), not for an evaluation of vestibular function.…”

Section: Other Diagnostic Testsmentioning

confidence: 99%

The Vestibular Implant

Berg¹

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Biallelic Intronic AAGGG Expansion of RFC1 is Related to Multiple System Atrophy

Wan

Chen

Wan

et al. 2020

Annals of Neurology

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Objective: A recessive biallelic repeat expansion, (AAGGG) exp , in the RFC1 gene has been reported to be a frequent cause of late-onset ataxia. For cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), the recessive biallelic (AAGGG) exp genotype was present in $92% of cases. This study aimed to examine whether the pentanucleotide repeat (PNR) was related to multiple system atrophy (MSA), which shares a spectrum of symptoms with CANVAS. Methods: In this study, we screened the pathogenic (AAGGG) exp repeat and 5 other PNRs in 104 Chinese sporadic adult-onset ataxia of unknown aetiology (SAOA) patients, 282 MSA patients, and 203 unaffected individuals. Multiple molecular genetic tests were used, including long-range polymerase chain reaction (PCR), repeat-primed PCR (RP-PCR), Sanger sequencing, and Southern blot. Comprehensive clinical assessments were conducted, including neurological examination, neuroimaging, nerve electrophysiology, and examination of vestibular function. Results: We identified biallelic (AAGGG) exp in 1 SAOA patient and 3 MSA patients. Additionally, 1 MSA patient had the (AAGGG) exp /(AAAGG) exp genotype with uncertain pathogenicity. We also described the carrier frequency for different PNRs in our cohorts. Furthermore, we summarized the distinct phenotypes of affected patients, suggesting that biallelic (AAGGG) exp in RFC1 could be associated with MSA and should be screened routinely in the MSA diagnostic workflow. Interpretation: Our results expanded the clinical phenotypic spectrum of RFC1-related disorders and raised the possibility that MSA might share the same genetic background as CANVAS, which is crucial for re-evaluating the current CANVAS and MSA diagnostic criteria.

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CANVAS an update: Clinical presentation, investigation and management

Cited by 83 publications

References 41 publications

Sweat Gland Denervation in Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS)

Sweat Gland Denervation in Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS)

The Vestibular Implant

Biallelic Intronic AAGGG Expansion of RFC1 is Related to Multiple System Atrophy

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