Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres

Abstract

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia

“…CANVAS is an adult-onset, slowly progressive neurological disorder characterized by imbalance, sensory neuropathy (neuronopathy), bilateral vestibulopathy 8 , chronic cough, and occasionally autonomic dysfunction 9 . Typically, sensory action potentials and somatosensory potentials are absent throughout, brain magnetic resonance imaging (MRI) shows cerebellar atrophy, and vestibular testing is consistent with impaired vestibular function bilaterally 9–17 . Late-onset ataxia and CANVAS are usually sporadic, but occasionally occur in siblings, raising the possibility of recessive transmission.…”

CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions

“…1) whose cause remains unexplained. The cough is reported up to 30 years before neurological onset [6,7], and it is hypothesised to be arising either as hypersensitivity syndrome due to a peripheral mechanism, where dysfunction of C fibres at level of upper way or oesophagus occurs; or due to cerebellar circuitry impairment [7]. Nerve conduction studies show non-length dependant sensory neuropathy in all the tested patients.…”

“…Comparison of disorders with similar clinical manifestations to CANVAS CANVAS, FA, SCA and MSA patients share a number of complaints which may include ataxia, sensory neuropathy, dysarthria and dysphagia[5][6][7][8][9][22][23][24][25] The first cohort originating from 11 families with a CAN-VAS diagnosis studied by Cortese et al consisted of 29 individuals of whom 23 were affected and six unaffected…”

Reversible conduction failure on the deep tendon reflex response recording in early Guillain-Barré syndrome

“…As observed here, absence of Achilles T-reflex combined with preservation of motor and sensory conduction parameters of lower-limb nerves and SEP from tibial nerve could suggest that RCF particularly involves afferent Ia fibers. Selective vulnerability of Ia fibers has been reported in a few neurologic syndromes (Infante et al, 2018). To establish if this is the case in early GBS further serial clinico-electrophysiological studies are needed.…”