title: Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the University of Melbourne (D.J.S.), Royal Victorian Eye & Ear Hospital, Melbourne, Australia; Department of Anatomical Pathology (C.A.M.), Alfred Hospital, Melbourne, Australia; Department of Forensic Medicine (M.L.R.), New South Wales Pathology, New South Wales, Australia; Department of Medicine (A.M.C.), Tauranga Hospital, Wellington, New Zealand; Department of Neurology (S.M.), Capital Coast Health, Wellington, New Zealand; Pathology (D.L.), Waikato Hospital, Hamilton, Waikato, New Zealand; Department of Neuroscience (L.R.), St Vincent's Hospital, Melbourne, Australia; Department of Neuroscience (E.S.), Monash University, Melbourne, Australia; and Department of Neurology (G.M.H.), Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Szmulewicz
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rodriguez
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Chancellor
authors.forename: Stuart
authors.initials: S
authors.lastname: Mossman
authors.forename: Duncan
authors.initials: D
authors.lastname: Lamont
authors.forename: Leslie
authors.initials: L
authors.lastname: Roberts
authors.forename: Elsdon
authors.initials: E
authors.lastname: Storey
authors.forename: G Michael
authors.initials: GM
authors.lastname: Halmagyi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002524:Cerebellar Ataxia / Q000473:pathology* / Q000503:physiopathology*; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009460:Neurologic Examination; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009759:Nystagmus, Pathologic / Q000503:physiopathology / Q000523:psychology; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology*; D012021:Reflex, Abnormal / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology*; D012438:Saccades / Q000502:physiology; D012678:Sensation Disorders / Q000473:pathology* / Q000503:physiopathology*; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology*; D013577:Syndrome; D012668:Trigeminal Ganglion / Q000473:pathology / Q000503:physiopathology; D014725:Vestibular Nerve / Q000473:pathology / Q000503:physiopathology