David Szmulewicz

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome: a histopathologic case report.

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) represents a widespread impairment of the various systems involved in balance: cerebellar, proprioceptive and vestibular1. The characteristic clinical sign of this syndrome is the impaired visually enhanced vestibulo-ocular reflex (VVOR), which represents combined impairment of the three compensatory eye movement reflexes, namely the vestibulo-ocular reflex (VOR), smooth pursuit (SP) and optokinetic reflex (OKR). From the neuro-otological viewpoint the remarkable feature is the severe loss of vestibular function with preservation of auditory function. It is not known whether the vestibular loss in CANVAS is of central (vestibular nucleus) or peripheral origin, and if peripheral, whether of sensory or of neural origin. We describe the otopathology in a case of CANVAS that demonstrated the vestibular loss to be the result of bilateral neuropathy of the vestibular (Scarpas) ganglion and nerve.

Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS

Objective: To elucidate the neuropathology in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS), a novel cerebellar ataxia comprised of the triad of cerebellar impairment, bilateral vestibular hypofunction, and a peripheral sensory deficit. Method: Brain and spinal neuropathology in 2 patients with CANVAS, together with brain and otopathology in another patient with CANVAS, were examined postmortem. Results: Spinal cord pathology demonstrated a marked dorsal root ganglionopathy with secondary tract degeneration. Cerebellar pathology showed loss of Purkinje cells, predominantly in the vermis. Conclusion: The likely underlying sensory pathology in CANVAS is loss of neurons from the dorsal root and V, VII, and VIII cranial nerve ganglia—in other words, it is a “neuronopathy” rather than a “neuropathy.” Clinically, CANVAS is a differential diagnosis for both spinocerebellar ataxia type 3 (or Machado-Joseph disease) and Friedreich ataxia. In addition, there are 6 sets of sibling pairs, implying that CANVAS is likely to be a late-onset recessive or autosomal dominant with reduced penetrance disorder, and identification of the culprit gene is currently a target of investigation.

Proposed diagnostic criteria for cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS)

Purpose of review:Diagnosis of ataxic disorders is an important clinical challenge upon which prognostication, management, patient solace, and, above all, the hope of future treatment all rely. Heritable diseases and the possibility of affected offspring carry the added burden of portending adverse health, social and financial ramifications. Recent findings:Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited multisystem ataxia compromising cerebellar, vestibular, and sensory function. It is not uncommon, but despite early attempts the genetic defect is yet to be identified. As the search for the causative gene continues, we have found it useful to further define this syndrome in terms of its likely phenotype. Summary:We propose staged diagnostic criteria based on the identified pathology in CANVAS. We envisage that these criteria will aid the clinician in diagnosing CANVAS and the researcher in further elucidating this complex disorder.

Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome.

Introduction: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibuloocular reflex. The somatosensory deficit contributes to a significant level of disability in CANVAS. Methods: This study was a neurophysiological investigation of 14 patients with CANVAS. Results: Findings revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H‐reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of 14 patients. Conclusions: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction. Muscle Nerve 51: 600–603, 2015Introduction: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibuloocular reflex. The somatosensory deficit contributes to a significant level of disability in CANVAS. Methods: This study was a neurophysiological investigation of 14 patients with CANVAS. Results: Findings revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H-reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of 14 patients. Conclusions: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction. Muscle Nerve 51: 600–603, 2015

CANVAS an update: Clinical presentation, investigation and management

BACKGROUND Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia Syndrome (CANVAS) is a multi-system ataxia which results in cerebellar ataxia, a bilateral vestibulopathy and a somatosensory deficit. This sensory deficit has recently been shown to be a neuronopathy, with marked dorsal root ganglia neuronal loss. The characteristic oculomotor clinical sign is an abnormal visually enhanced vestibulo-ocular reflex. OBJECTIVE To outline the expanding understanding of the pathology in this condition, as well as diagnostic and management issues encountered in clinical practice. METHODS Retrospective data on 80 CANVAS patients is reviewed. RESULTS In addition to the triad of cerebellar impairment, bilateral vestibulopathy and a somatosensory deficit, CANVAS patients may also present with orthostatic hypotension, a chronic cough and neuropathic pain. Management of falls risk and dysphagia is a major clinical priority. CONCLUSIONS CANVAS is an increasingly recognised cause of late-onset ataxia and disequilibrium, and is likely to be a recessive disorder.

Clinical characteristics and treatment choice in vestibular migraine

This retrospective review aims to survey the clinical characteristics and management of vestibular migraine (VM) patients seen in a tertiary hospital multi-disciplinary balance disorders clinic, and how this aligns with the evidence base in the literature. A single investigator reviewed the medical records of the patients who presented to a tertiary hospital balance disorders clinic over a four month period and identified 90 cases of VM. The mean age of patients with a diagnosis of VM was 50 years (range of 17-84) and 72 (80%) were female. Vertigo (96%) and headache (60%) were the predominate symptoms. Vestibular function testing abnormalities included six (5%) with a positive video head impulse test and seven (6%) with oculomotor abnormalities. Pizotifen (30%) and amitriptyline (21%) were the two most commonly used medications whilst only 14 (16%) received vestibular physiotherapy. This study suggests that VM is a very common presentation to a tertiary balance disorders clinic, but there is little consensus in choice of initial management and vestibular rehabilitation is underutilized. This data may be valuable in informing the practice of neuro-otology as well as in the planning of future service provision.

Combined Central and Peripheral Degenerative Vestibular Disorders: CANVAS, Idiopathic Cerebellar Ataxia with Bilateral Vestibulopathy (CABV) and Other Differential Diagnoses of the CABV Phenotype

Purpose of ReviewThe traditional dichotomy of central versus peripheral causes of imbalance may be viewed as an obstacle, rather than an aid to diagnosis. This paper aims to review the clinical assessment of conditions with combined central and peripheral vestibular impairment and the more common conditions which may manifest this joint pathology.Recent FindingsCerebellar ataxia with bilateral vestibulopathy (CABV) was initially believed to be a distinct syndrome but has more recently been recognised as a phenotype which may be found in a number of disorders including CANVAS, Friedreich’s ataxia, spinocerebellar ataxia types 3 and 6 and multiple system atrophy. Oculomotor assessment provides a valuable means of identifying such patients and centres around the identification of an abnormal visually enhanced vestibulo-ocular reflex.SummaryIdentification of the CABV phenotype limits the differential diagnoses and then provides a directed investigation pathway.