Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia 'CANVAS' syndrome

Abstract

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also found a higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We confirmed that sensory findings on nerve conduction tests were consistent with a sensory ganglionopathy and describe two patients with loss of trigeminal sensation consistent with previous pathological descriptions of trigeminal sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major feature of CANVAS. This has implications for the management of patients with CANVAS as the autonomic symptoms may be amenable to treatment. The findings also provide an important differential diagnosis from multiple system atrophy for patients who present with ataxia and autonomic failure.

Isolated Vestibular Suppression Impairment With Vestibular Migraine

“…Other recognized genetic causes of a similar syndrome have been excluded, but a specific mutation has not yet been identified in this kindred or in CANVAS more generally (2). In our patient, there is clear evidence of sensory neuropathy: proband for typical neuropathic symptoms; expected abnormalities on physical examination; abnormal sural nerve biopsy; and dysphagia indicating likely autonomic involvement (2,3). Cerebellar dysfunction is suggested by impaired suppression of caloric nystagmus and abnormal SP and VORS.…”

“…Cerebellar Ataxia with Neuropathy and Vestibular Areflexia (CANVAS) is a recently described syndrome (1) that is proving to be a not uncommon cause of ataxia (2,3). It is characterized by a number of features: relatively selective cerebellar atrophy (4); sensory loss because of neuronopathy with degeneration of dorsal root ganglia and posterior columns (4); vestibular loss because of degeneration of Scarpa's (vestibular) ganglia (4); autonomic involvement (2,3).The clinical diagnosis of sensory neuropathy, rather than neuronopathy, will be used throughout this article, given that neuronopathy has not been pathologically established in any patient within the kindred.…”

“…It is characterized by a number of features: relatively selective cerebellar atrophy (4); sensory loss because of neuronopathy with degeneration of dorsal root ganglia and posterior columns (4); vestibular loss because of degeneration of Scarpa's (vestibular) ganglia (4); autonomic involvement (2,3).The clinical diagnosis of sensory neuropathy, rather than neuronopathy, will be used throughout this article, given that neuronopathy has not been pathologically established in any patient within the kindred. A recent report indicates that CANVAS is likely to have a genetic basis in many patients, with 13 kindreds noted among 80 affected individuals (2).…”

Corrigendum

“…We reported abnormal heart rate response-to deep breathing in 10 (48%) patients, and to standing in 8 (36%) patientswith abnormal Valsalva ratio in 9 (41%) patients in our published article (Wu et al, 2014). These differ from the figures quoted by Krismer and Wenning which were: abnormal heart rate response-to deep breathing in 11 (52%) patients, and to standing in 10 (45%) of the patients-and abnormal Valsalva ratio in 10 (45%) patients.…”

“…The authors wish to draw attention to, and account for the differences in the individual para-sympathetic results quoted in our paper (Wu et al, 2014) to those quoted in the expert scientific commentary by Krismer and Wenning (2014).…”