Andrew Chancellor

Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome

Objective: The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features. Methods: Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia. Results: The reported age at onset range was 39–71 years, and symptom duration was 3–38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared. Conclusions: Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS).

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis

The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a distinct syndrome with a characteristic and measurable clinical sign—an absent visually enhanced vestibulo‐ocular reflex—in 2004. We reviewed 27 patients with this syndrome and show that a non‐length‐dependent sensory deficit with absent sensory nerve action potentials is an integral component of this syndrome, which we now call “cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome” (CANVAS). All patients had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I. Brain and temporal bone pathology in one patient showed marked loss of Purkinje cells and of vestibular, trigeminal, and facial ganglion cells, but not of spiral ganglion cells. There are two sets of sibling pairs, suggesting CANVAS is a late‐onset recessive disorder. The characteristic clinical sign—the visual vestibulo‐ocular reflex deficit—can be demonstrated and measured clinically using video‐oculography.

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.

Peripheral nerve ultrasound in cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS)

We report preliminary findings of nerve ultrasound in patients with cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) who have sensory impairment due to dorsal root ganglionopathy.

Peripheral nerve ultrasound findings in mucolipidosis type 3

PurposeThe mucolipidoses are rare autosomal recessive lysosomal storage disorders. Neurologic involvement in these conditions is generally thought to be limited to cognitive delay and entrapment neuropathies (primarily carpal tunnel syndrome). We sought to evaluate peripheral nerves in this condition using nerve ultrasound.MethodsWe performed peripheral nerve ultrasound in two siblings with genetically confirmed mucolipidosis type 3 (alpha/beta).ResultsPeripheral nerves in mucolipidosis type 3 (alpha/beta) exhibit multifocal enlargement.ConclusionThe peripheral nerve ultrasound has a role in the evaluation of this, and possibly other lysosomal storage disorders.

Ulnar neuropathy with abnormal non-localizing electrophysiology: Clinical, electrophysiological and ultrasound findings

OBJECTIVE To systematically study demographic, clinical, electrophysiological and nerve ultrasound characteristics of ulnar neuropathy with abnormal non-localizing electrophysiology (NL-UN) and further define the utility of ultrasound over and above the conventional electro-diagnostic approach. METHOD NL-UNs were prospectively identified from 113 consecutive referrals with suspected ulnar neuropathy. All received electro-diagnostic tests and ulnar nerve ultrasound. NL-UN severity was graded using clinical and electrophysiological scales. RESULTS In 64 of 113 referrals, an ulnar mono- neuropathy was confirmed by electrophysiology. Sixteen of these 64 (25%) had NL-UN, predominantly males (14 out of 16 patients) with severe or moderate clinical and electrophysiological ratings. Ultrasound showed focal ulnar neuropathy at the elbow in 13 out of 16, and diffuse ulnar nerve abnormality in three, and identified a likely or possible causative mechanism in 11. CONCLUSION A significant proportion (a quarter) of ulnar neuropathies with abnormal electrophysiology were NL-UN, of heterogeneous etiology; the majority were males with significant disability and axonal loss. Ultrasound had a significant role in localization and classification that facilitated management. SIGNIFICANCE To our knowledge, this is the first systematic prospective study that analyzes the demographic, clinical, electrophysiological and ultrasound characteristics of NL-UN in a routine clinical neurophysiology setting.

F33. Cross sectional peripheral nerve area in canvas syndrome (cerebellar ataxia neuropathy vestibular areflexia syndrome)

Introduction Patients with Cerebellar Ataxia Neuropathy Vestibular Areflexia Syndrome (CANVAS) have sensory impairment due to dorsal root ganglionopathy. After preliminary findings of small nerves on ultrasound in CANVAS, we sought to systematically study a larger cohort of CANVAS patients to see if this is a feature of this ganglionopathy and thus distinct from the ultrasound findings in axonal neuropathy. Methods The ultrasound cross sectional area (CSA) of median and ulnar nerves of 14 CANVAS patients was compared with 14 age- and gender-matched healthy controls (HCONT) and 14 age-and gender-matched patients with acquired axonal neuropathy (PNCONT). The individual CSAs of CANVAS and PNCONT patients were also compared with the mean CSA of our reference population. Results The nerve CSA of CANVAS patients was significantly smaller than the CSA of both HCONT and PNCONT at all sites ( P > 2 SDs below a reference mean. Conclusion The small nerves in CANVAS probably reflect nerve thinning from axonal loss secondary to ganglion cell loss. This is in contradistinction to the ultrasound abnormality in PNCONT, in which the nerves are mildly enlarged. Our data show a role for ultrasound in the diagnosis of CANVAS ganglionopathy. This may also be applicable to sensory neuronopathy from other causes.

Cross sectional peripheral nerve area in cerebellar ataxia neuropathy vestibular areflexia syndrome (canvas)

Objectives Patients with cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) have sensory impairment due to dorsal root ganglionopathy. After preliminary findings of small nerves on ultrasound in CANVAS, we sought to systematically study a larger cohort of CANVAS patients to see if this is a feature of this ganglionopathy and thus distinct from the ultrasound findings in axonal neuropathy. Methods The ultrasound cross sectional area (CSA) of median and ulnar nerves of 14 CANVAS patients was compared with 14 age- and gender-matched healthy controls (HC) and 14 age-and gender-matched patients with acquired axonal neuropathy (AxPN). The individual CSAs of CANVAS and AxPN patients were also compared with the mean CSA of our reference population. Results The nerve CSA of CANVAS patients was significantly smaller than the CSA of both HC and AxPN at all sites (p<0.00001). By contrast, the CSA of AxPN was mildly larger than the HC CSA at all sites (p<0.05). All but one individual measurement of CSA at mid-forearm level in the CANVAS patients fell outside the normal control range and was >2 SDs below a reference mean. Conclusions The small nerves in CANVAS probably reflect nerve thinning from axonal loss secondary to ganglion cell loss. This is in contradistinction to the ultrasound abnormality in AxNP, in which the nerves are mildly enlarged. Our data show a role for ultrasound in the diagnosis of CANVAS ganglionopathy. This may also be applicable to ganglionopathy from other causes.