3. Introduction
• Relatively new condition
• Emerge during the last 30 years
• 2011 named CANVAS
• 2016 diagnostic criteria
• 2019 Cortese et al. identified a recessive repeat expansion in intron 2 of
RFC1 as the main cause of CANVAS
Szmulewicz DJ, Waterston JA, Halmagyi GM, Mossman S, Chancellor AM, McLean CA, et al. Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome. Neurology. 2011;76(22):1903–10.
Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, et al. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet. 2019;51(4):649–58.
4. Szmulewicz DJ, Waterston JA, MacDougall HG, Mossman S, Chancellor AM, McLean CA, et al. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of
the clinical features and video-oculographic diagnosis. Ann N Y Acad Sci. 2011;1233:139–47.
5.
6. Neuroimaging
Dupré M, Hermann R, Tilikete CF. Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS). The Cerebellum. 2020 Oct 4:1-4.
7. Differential Diagnosis
• Known Genetic Disorders such as Friedreich ataxia, SCAs, mainly SCA3 and
SCA1 and other phenotypes of mitochondrial diseases
• Multiple System Atrophy
• Unspecific Neuropathy with Vestibular Deficit or with Chronic Cough
• Alcohol intoxication
Dupré M, Hermann R, Tilikete CF. Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS). The Cerebellum. 2020 Oct 4:1-4.
8. Neuropathology
• Severe axonal neuropathy, predominantly in myelinated fibres, with non
significant regeneration and no active axonal degeneration, no demyelination
• Severe atrophy of dorsal root and posterior column
• Pukinje cell loss
Dupré M, Hermann R, Tilikete CF. Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS). The Cerebellum. 2020 Oct 4:1-4.
9. Physiopathology
• A mutation in a polymorphic zone, favouring during evolution the
expansion of repeats modifying the expression of a gene coding for a protein
involved in DNA repair, leading to damage to the most vulnerable tissues,
notably the cerebellum and peripheral nerves, in particular the small fibres
(Aδ and C)
Dupré M, Hermann R, Tilikete CF. Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS). The Cerebellum. 2020 Oct 4:1-4.