Journal of Neurology

, Volume 265, Issue 6, pp 1402–1409 | Cite as

CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA)

  • Rocio Garcia-Santibanez
  • Craig M. Zaidman
  • R. Brian Sommerville
  • Glenn Lopate
  • Conrad C. Weihl
  • Alan Pestronk
  • Robert C. Bucelli
Original Communication



CANOMAD/CANDA are syndromes characterized by ataxic neuropathy, ophthalmoplegia, monoclonal gammopathy, cold agglutinins and disialosyl antibodies.


A retrospective review of our neuromuscular autoantibody panel database was performed. Anti-GD1b seropositive patients with ataxia were included.


Eleven patients were identified. Median age at onset was 56 years. Median disease duration was 6 years. All patients had gait disorders. Nine had ocular motility abnormalities. Most had a monoclonal protein and all had elevated serum IgM. Electrodiagnostic studies showed a mixed axonal/demyelinating pattern (6), an axonal pattern (4), or a pure demyelinating pattern (1). Ultrasounds showed nerve enlargement patterns consistent with acquired demyelination. A nerve biopsy showed near complete loss of myelinated axons with preservation of smaller axons. Rituximab was the most effective immunotherapy.


CANOMAD/CANDA are rare and debilitating disorders with characteristic clinical and diagnostic findings. In our cohort, nerve ultrasound showed regional nerve enlargement and rituximab was the most effective immunomodulatory therapy.


Ataxic neuropathies Disialosyl antibodies CANOMAD CANDA Ultrasound Immune therapy 



No grant support or funding for this article.

Compliance with ethical standards

Ethical standards

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Conflicts of interest

All authors have no conflicts of interest.

Supplementary material

415_2018_8853_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 22 kb)


  1. 1.
    Pestronk A, Chuquilin M, Choksi R (2010) Motor neuropathies and serum IgM binding to NS6S heparin disaccharide or GM1 ganglioside. J Neurol Neurosurg Psychiatry 81:726–730CrossRefPubMedGoogle Scholar
  2. 2.
    Pestronk A, Choksi R, Logigian E, Al-Lozi MT (2003) Sensory neuropathy with monoclonal IgM binding to a trisulfated heparin disaccharide. Muscle Nerve 27:188–195CrossRefPubMedGoogle Scholar
  3. 3.
    Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) (1991) Report from an Ad Hoc subcommittee of the American Academy of Neurology AIDS task force. Neurology 41:617–618CrossRefGoogle Scholar
  4. 4.
    Zaidman CM, Al-Lozi M, Pestronk A (2009) Peripheral nerve size in normals and patients with polyneuropathy: an ultrasound study. Muscle Nerve 40:960–966CrossRefPubMedGoogle Scholar
  5. 5.
    Willison HJ, Paterson G, Veitch J, Inglis G, Barnett SC (1993) Peripheral neuropathy associated with monoclonal IgM anti-Pr2 cold agglutinins. J Neurol Neurosurg Psychiatry 56:1178–1183CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Takada K, Shimizu J, Kusunoki S (2008) Apoptosis of primary sensory neurons in GD1b-induced sensory ataxic neuropathy. Exp Neurol 209:279–283CrossRefPubMedGoogle Scholar
  7. 7.
    McKelvie PA, Gates PC, Day T (2013) Canomad: report of a case with a 40-year history and autopsy. Is this a sensory ganglionopathy with neuromuscular junction blockade? Muscle Nerve 48:599–603CrossRefPubMedGoogle Scholar
  8. 8.
    Obi T, Murakami T, Takatsu M et al (1999) Clinicopathological study of an autopsy case with sensory-dominant polyradiculoneuropathy with antiganglioside antibodies. Muscle Nerve 22:1426–1431CrossRefPubMedGoogle Scholar
  9. 9.
    Clark AJ, Kaller MS, Galino J, Willison HJ, Rinaldi S, Bennett DLH (2017) Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination. Brain 140:898–913CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Willison HJ, O’Leary CP, Veitch J et al (2001) The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies. Brain 124:1968–1977CrossRefPubMedGoogle Scholar
  11. 11.
    Attarian S, Boucraut J, Hubert AM et al (2010) Chronic ataxic neuropathies associated with anti-GD1b IgM antibodies: response to IVIg therapy. J Neurol Neurosurg Psychiatry 81:61–64CrossRefPubMedGoogle Scholar
  12. 12.
    Pestronk A, Schmidt RE, Choksi RM, Sommerville RB, Al-Lozi MT (2012) Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS. Muscle Nerve 45:866–872CrossRefPubMedGoogle Scholar
  13. 13.
    Erb S, Ferracin F, Fuhr P et al (2000) Polyneuropathy attributes: a comparison between patients with anti-MAG and anti-sulfatide antibodies. J Neurol 247:767–772CrossRefPubMedGoogle Scholar
  14. 14.
    Goedee HS, van der Pol WL, van Asseldonk JH et al (2017) Diagnostic value of sonography in treatment-naive chronic inflammatory neuropathies. Neurology 88:143–151CrossRefPubMedGoogle Scholar
  15. 15.
    Padua L, Granata G, Sabatelli M et al (2014) Heterogeneity of root and nerve ultrasound pattern in CIDP patients. Clin Neurophysiol 125:160–165CrossRefPubMedGoogle Scholar
  16. 16.
    Siddiqui K, Cahalane E, Keogan M, Hardiman O (2003) Chronic ataxic neuropathy with cold agglutinins: atypical phenotype and response to anti-CD20 antibodies. Neurology 61:1307–1308CrossRefPubMedGoogle Scholar
  17. 17.
    Loscher WN, Woertz A, Wallnofer M, Wanschitz JV, Luef G (2013) Successful treatment of CANOMAD with IVIg and rituximab. J Neurol 260:1168–1170CrossRefPubMedGoogle Scholar
  18. 18.
    Delmont E, Jeandel PY, Hubert AM, Marcq L, Boucraut J, Desnuelle C (2010) Successful treatment with rituximab of one patient with CANOMAD neuropathy. J Neurol 257:655–657CrossRefPubMedGoogle Scholar
  19. 19.
    Kam C, Balaratnam MS, Purves A et al (2011) Canomad presenting without ophthalmoplegia and responding to intravenous immunoglobulin. Muscle Nerve 44:829–833CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Rocio Garcia-Santibanez
    • 1
  • Craig M. Zaidman
    • 1
  • R. Brian Sommerville
    • 1
  • Glenn Lopate
    • 1
  • Conrad C. Weihl
    • 1
  • Alan Pestronk
    • 1
  • Robert C. Bucelli
    • 1
  1. 1.Division of Neuromuscular Medicine, Department of NeurologyWashington University in St. LouisSt. LouisUSA

Personalised recommendations