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Published in: Journal of Neurology 8/2020

01-08-2020 | Lymphoma | Original Communication

Sustained response to subcutaneous immunoglobulins in chronic ataxic neuropathy with anti-disialosyl IgM antibodies (CANDA): report of two cases and review of the literature

Authors: D. Marastoni, L. Africa, A. Peretti, S. Bocci, L. Insana, S. Ferrari, F. Ginanneschi, G. Zanette, G. M. Fabrizi, F. Giannini

Published in: Journal of Neurology | Issue 8/2020

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Abstract

Introduction

Chronic ataxic neuropathy with anti-disialosyl IgM antibodies (CANDA) is a rare disorder for which the pathological, neurophysiological, and therapeutic evidence remains anecdotal and controversial.

Methods

This report on CANDA focuses on the neurophysiological patterns and treatment responses shared by two cases. One patient underwent nerve ultrasound follow-up. A comprehensive review of the literature highlighted the diverse experiences with different treatment options.

Results

Response to different therapies was similar in both patients: intravenous immunoglobulins achieved a favorable response albeit with significant wearing-off fluctuations; treatment with subcutaneous immunoglobulins (SCIg) was an effective alternative leading to a clinical response for at least 2 years. Rituximab, which was trialed in both patients, was not continued long enough to determine its efficacy in modifying the disease course and/or modulating responsiveness to immunoglobulins. Steroids caused clinical worsening in both patients.

Conclusions

Immunoglobulin therapy appeared as the most effective in the treatment of these two patients. SCIg provided an effective treatment option for the long-term management of CANDA.
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Literature
1.
go back to reference 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 124:1968–1977PubMed 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 124:1968–1977PubMed
2.
go back to reference Yuki N, Uncini A (2014) Acute and chronic ataxic neuropathies with disialosyl antibodies: a continuous clinical spectrum and a common pathophysiological mechanism. Muscle Nerve 49(5):629–635PubMed Yuki N, Uncini A (2014) Acute and chronic ataxic neuropathies with disialosyl antibodies: a continuous clinical spectrum and a common pathophysiological mechanism. Muscle Nerve 49(5):629–635PubMed
3.
go back to reference Kusunoki S, Mashiko H, Mochizuki N, Chiba A, Arita M, Hitoshi S, Kanazawa I (1997) Binding of antibodies against GM1 and GD1b in human peripheral nerve. Muscle Nerve 20(7):840–845PubMed Kusunoki S, Mashiko H, Mochizuki N, Chiba A, Arita M, Hitoshi S, Kanazawa I (1997) Binding of antibodies against GM1 and GD1b in human peripheral nerve. Muscle Nerve 20(7):840–845PubMed
4.
go back to reference Liu JX, Willison HJ, Pedrosa-Domellöf F (2009) Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles. Invest Ophthalmol Vis Sci 50(7):3226–3232PubMed Liu JX, Willison HJ, Pedrosa-Domellöf F (2009) Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles. Invest Ophthalmol Vis Sci 50(7):3226–3232PubMed
5.
go back to reference Plomp JJ, Willison HJ (2009) Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction. J Physiol 587:3979–3999PubMedPubMedCentral Plomp JJ, Willison HJ (2009) Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction. J Physiol 587:3979–3999PubMedPubMedCentral
6.
go back to reference Gong Y, Tagawa Y, Lunn MP et al (2002) Localization of major gangliosides in the PNS: implications for immune neuropathies. Brain 125:2491–2506PubMed Gong Y, Tagawa Y, Lunn MP et al (2002) Localization of major gangliosides in the PNS: implications for immune neuropathies. Brain 125:2491–2506PubMed
7.
go back to reference Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force (1991) Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Neurology 41:617–618 Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force (1991) Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Neurology 41:617–618
8.
go back to reference Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society–first revision. J Peripher Nerv Syst 15(1):1–9 Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society–first revision. J Peripher Nerv Syst 15(1):1–9
9.
go back to reference Fabrizi GM, Tamburin S, Cavallaro T et al (2018) The spectrum of Charcot–Marie–Tooth disease due to myelin protein zero: an electrodiagnostic, nerve ultrasound and histological study. Clin Neurophysiol 129(1):21–32PubMed Fabrizi GM, Tamburin S, Cavallaro T et al (2018) The spectrum of Charcot–Marie–Tooth disease due to myelin protein zero: an electrodiagnostic, nerve ultrasound and histological study. Clin Neurophysiol 129(1):21–32PubMed
10.
go back to reference Franciotta D, Gastaldi M, Benedetti L et al (2017) Diagnostics of dysimmune peripheral neuropathies. Neurol Sci 38(Suppl 2):243–247PubMed Franciotta D, Gastaldi M, Benedetti L et al (2017) Diagnostics of dysimmune peripheral neuropathies. Neurol Sci 38(Suppl 2):243–247PubMed
11.
go back to reference 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(4):599–603PubMed 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(4):599–603PubMed
12.
go back to reference 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(10):1426–1431PubMed 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(10):1426–1431PubMed
13.
go back to reference Yuki N, Miyatani N, Sato S et al (1992) Acute relapsing sensory neuropathy associated with IgM antibody against B-series gangliosides containing a GalNAc beta 1–4(Gal3-2 alpha NeuAc8-2 alpha NeuAc)beta 1 configuration. Neurology 42(3 Pt 1):686–689PubMed Yuki N, Miyatani N, Sato S et al (1992) Acute relapsing sensory neuropathy associated with IgM antibody against B-series gangliosides containing a GalNAc beta 1–4(Gal3-2 alpha NeuAc8-2 alpha NeuAc)beta 1 configuration. Neurology 42(3 Pt 1):686–689PubMed
14.
go back to reference Kam C, Balaratnam MS, Purves A et al (2011) Canomad presenting without ophthalmoplegia and responding to intravenous immunoglobulin. Muscle Nerve 44(5):829–833PubMed Kam C, Balaratnam MS, Purves A et al (2011) Canomad presenting without ophthalmoplegia and responding to intravenous immunoglobulin. Muscle Nerve 44(5):829–833PubMed
15.
go back to reference Arbogast SD, Khanna S, Koontz DW, Tomsak RL, Katirji B, Leigh RJ (2007) Chronic ataxic neuropathy mimicking dorsal midbrain syndrome. J Neurol Neurosurg Psychiatry 78(11):1276–1277PubMedPubMedCentral Arbogast SD, Khanna S, Koontz DW, Tomsak RL, Katirji B, Leigh RJ (2007) Chronic ataxic neuropathy mimicking dorsal midbrain syndrome. J Neurol Neurosurg Psychiatry 78(11):1276–1277PubMedPubMedCentral
16.
go back to reference Garcia-Santibanez R, Zaidman CM, Sommerville RB, Lopate G, Weihl CC, Pestronk A (2018) CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA). J Neurol 265(6):1402–1409PubMed Garcia-Santibanez R, Zaidman CM, Sommerville RB, Lopate G, Weihl CC, Pestronk A (2018) CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA). J Neurol 265(6):1402–1409PubMed
17.
go back to reference 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(4):898–913PubMedPubMedCentral 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(4):898–913PubMedPubMedCentral
18.
go back to reference Telleman IA, Grimm A, Goedee S, Visser LH, Zaidman CM (2018) Nerve ultrasound in polyneuropathies. Muscle Nerve 57(5):716–728PubMed Telleman IA, Grimm A, Goedee S, Visser LH, Zaidman CM (2018) Nerve ultrasound in polyneuropathies. Muscle Nerve 57(5):716–728PubMed
19.
go back to reference 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(1):61–64PubMed 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(1):61–64PubMed
20.
go back to reference 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(4):655–657PubMed 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(4):655–657PubMed
21.
go back to reference Löscher WN, Woertz A, Wallnöfer M, Wanschitz JV, Luef G (2013) Successful treatment of CANOMAD with IVIg and rituximab. J Neurol 260(4):1168–1170PubMed Löscher WN, Woertz A, Wallnöfer M, Wanschitz JV, Luef G (2013) Successful treatment of CANOMAD with IVIg and rituximab. J Neurol 260(4):1168–1170PubMed
23.
go back to reference Lehmann HC, Hartung HP (2011) Plasma exchange and intravenous immunoglobulins: mechanism of action in immune-mediated neuropathies. J Neuroimmunol 231:61–69PubMed Lehmann HC, Hartung HP (2011) Plasma exchange and intravenous immunoglobulins: mechanism of action in immune-mediated neuropathies. J Neuroimmunol 231:61–69PubMed
24.
go back to reference Halstead SK, O'Hanlon GM, Humphreys PD et al (2004) Anti-disialoside antibodies kill perisynaptic Schwann cells and damage motor nerve terminals via membrane attack complex in a murine model of neuropathy. Brain 127(Pt 9):2109–2123PubMed Halstead SK, O'Hanlon GM, Humphreys PD et al (2004) Anti-disialoside antibodies kill perisynaptic Schwann cells and damage motor nerve terminals via membrane attack complex in a murine model of neuropathy. Brain 127(Pt 9):2109–2123PubMed
25.
go back to reference McGonigal R, Rowan EG, Greenshields KN et al (2010) Anti-GD1a antibodies activate complement and calpain to injure distal motor nodes of Ranvier in mice. Brain 133:1944–1960PubMed McGonigal R, Rowan EG, Greenshields KN et al (2010) Anti-GD1a antibodies activate complement and calpain to injure distal motor nodes of Ranvier in mice. Brain 133:1944–1960PubMed
26.
go back to reference Sala TP, Crave JC, Duracinsky M, Lepira Bompeka F, Tadmouri A, Chassany O, Cherin P (2018) Efficacy and patient satisfaction in the use of subcutaneous immunoglobulin immunotherapy for the treatment of auto-immune neuromuscular diseases. Autoimmun Rev 17(9):873–881PubMed Sala TP, Crave JC, Duracinsky M, Lepira Bompeka F, Tadmouri A, Chassany O, Cherin P (2018) Efficacy and patient satisfaction in the use of subcutaneous immunoglobulin immunotherapy for the treatment of auto-immune neuromuscular diseases. Autoimmun Rev 17(9):873–881PubMed
27.
go back to reference Misbah S, Sturzenegger MH, Borte M, Shapiro RS, Wasserman RL, Berger M, Ochs HD (2009) Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol 158(Suppl 1):51–59PubMedPubMedCentral Misbah S, Sturzenegger MH, Borte M, Shapiro RS, Wasserman RL, Berger M, Ochs HD (2009) Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol 158(Suppl 1):51–59PubMedPubMedCentral
28.
go back to reference Racosta JM, Sposato LA, Kimpinski K (2017) Subcutaneous versus intravenous immunoglobulin for chronic autoimmune neuropathies: a meta-analysis. Muscle Nerve 55(6):802–809PubMed Racosta JM, Sposato LA, Kimpinski K (2017) Subcutaneous versus intravenous immunoglobulin for chronic autoimmune neuropathies: a meta-analysis. Muscle Nerve 55(6):802–809PubMed
29.
go back to reference van Schaik IN, Bril V, van Geloven N et al (2018) Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 17:35–46PubMed van Schaik IN, Bril V, van Geloven N et al (2018) Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 17:35–46PubMed
30.
go back to reference Nobile-Orazio E, Gallia F, Terenghi F, Bianco M (2017) Comparing treatment options for chronic inflammatory neuropathies and choosing the right treatment plan. Expert Rev Neurother 17(8):755–765PubMed Nobile-Orazio E, Gallia F, Terenghi F, Bianco M (2017) Comparing treatment options for chronic inflammatory neuropathies and choosing the right treatment plan. Expert Rev Neurother 17(8):755–765PubMed
31.
go back to reference Cocito D, Merola A, Romagnolo A et al (2016) Subcutaneous immuno-globulin in CIDP and MMN: a different long-term clinical response? J Neurol Neurosurg Psychiatry 87(7):791–793PubMed Cocito D, Merola A, Romagnolo A et al (2016) Subcutaneous immuno-globulin in CIDP and MMN: a different long-term clinical response? J Neurol Neurosurg Psychiatry 87(7):791–793PubMed
32.
go back to reference 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(9):1307–1308PubMed 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(9):1307–1308PubMed
33.
go back to reference Boussaïd I, Bouhour F, Vial C, Caudie C (2011) Identification and characterization of a monoclonal IgM reacting with disialylated gangliosides recognizing the CANOMAD syndrome. Ann Biol Clin (Paris) 69(4):476–480 Boussaïd I, Bouhour F, Vial C, Caudie C (2011) Identification and characterization of a monoclonal IgM reacting with disialylated gangliosides recognizing the CANOMAD syndrome. Ann Biol Clin (Paris) 69(4):476–480
34.
go back to reference Delval A, Stojkovic T, de Sèze J et al (2004) Ataxic neuropathy associated with disialosylated antibodies: description of new clinical and biochemical forms. Rev Neurol (Paris) 160(10):910–916 Delval A, Stojkovic T, de Sèze J et al (2004) Ataxic neuropathy associated with disialosylated antibodies: description of new clinical and biochemical forms. Rev Neurol (Paris) 160(10):910–916
35.
go back to reference Sanvito L, Rajabally YA (2011) Optic neuropathy associated with CANOMAD: description of 2 cases. Muscle Nerve 44(3):451–455PubMed Sanvito L, Rajabally YA (2011) Optic neuropathy associated with CANOMAD: description of 2 cases. Muscle Nerve 44(3):451–455PubMed
36.
go back to reference Paradas C, Morgado Y, Gallardo E, Juarez C, Rojas-Garcia R (2011) Prednisone can worsen ataxic neuropathy with anti-disialosyl IgM antibodies. Muscle Nerve 44(5):839–841PubMed Paradas C, Morgado Y, Gallardo E, Juarez C, Rojas-Garcia R (2011) Prednisone can worsen ataxic neuropathy with anti-disialosyl IgM antibodies. Muscle Nerve 44(5):839–841PubMed
37.
go back to reference Serrano-Munuera C, Rojas-García R, Gallardo E et al (2002) Antidisialosyl antibodies in chronic idiopathic ataxic neuropathy. J Neurol 249:1525–1528PubMed Serrano-Munuera C, Rojas-García R, Gallardo E et al (2002) Antidisialosyl antibodies in chronic idiopathic ataxic neuropathy. J Neurol 249:1525–1528PubMed
38.
go back to reference Johnson K, Malkan A, Shaffi M (2015) Facial involuntary movements and respiratory failure in CANOMAD, responsive to IVIG therapy. Case Rep Med 2015:170543PubMedPubMedCentral Johnson K, Malkan A, Shaffi M (2015) Facial involuntary movements and respiratory failure in CANOMAD, responsive to IVIG therapy. Case Rep Med 2015:170543PubMedPubMedCentral
39.
go back to reference Iorio R, Capone F, Iannaccone E, Willison HJ, Modoni A, Tonali PA, Silvestri G (2009) SIADH in a patient with sensory ataxic neuropathy with anti-disialosyl antibodies (CANOMAD). J Neurol 256(7):1177–1179PubMed Iorio R, Capone F, Iannaccone E, Willison HJ, Modoni A, Tonali PA, Silvestri G (2009) SIADH in a patient with sensory ataxic neuropathy with anti-disialosyl antibodies (CANOMAD). J Neurol 256(7):1177–1179PubMed
40.
go back to reference Taguchi Y, Takashima S, Kusunoki S, Asaoka E, Inoue H (2003) Chronic sensory ataxic neuropathy with polyclonal IgM reactivity to various disialosyl gangliosides. Muscle Nerve 28(1):128–129PubMed Taguchi Y, Takashima S, Kusunoki S, Asaoka E, Inoue H (2003) Chronic sensory ataxic neuropathy with polyclonal IgM reactivity to various disialosyl gangliosides. Muscle Nerve 28(1):128–129PubMed
41.
go back to reference Delval A, Stojkovic T, Vermersch P (2006) Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis. Muscle Nerve 33(2):274–277PubMed Delval A, Stojkovic T, Vermersch P (2006) Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis. Muscle Nerve 33(2):274–277PubMed
42.
go back to reference Shihashi G, Yagi T, Suzuki S et al (2015) Immune-mediated neuropathy with anti-disialosyl IgM antibodies in diffuse large B-cell lymphoma: a case report and literature review. Intern Med 54(13):1647–1651PubMed Shihashi G, Yagi T, Suzuki S et al (2015) Immune-mediated neuropathy with anti-disialosyl IgM antibodies in diffuse large B-cell lymphoma: a case report and literature review. Intern Med 54(13):1647–1651PubMed
43.
go back to reference Barnett MH, Barnett Y, Burke D, Willison H (2011) Neurological picture. Spinal nerve root hypertrophy in chronic ataxic neuropathy with antiglycolipid IgM antibodies. J Neurol Neurosurg Psychiatry 82(1):97PubMed Barnett MH, Barnett Y, Burke D, Willison H (2011) Neurological picture. Spinal nerve root hypertrophy in chronic ataxic neuropathy with antiglycolipid IgM antibodies. J Neurol Neurosurg Psychiatry 82(1):97PubMed
44.
go back to reference Furiya Y, Hirano M, Kusunoki S, Ueda M, Sugie K, Nishiwaki T, Ueno S (2008) Complete recovery of an aged patient with Guillan–Barré syndrome associated with multiple IgM anti-ganglioside antibodies. Muscle Nerve 38(6):1630–1633PubMed Furiya Y, Hirano M, Kusunoki S, Ueda M, Sugie K, Nishiwaki T, Ueno S (2008) Complete recovery of an aged patient with Guillan–Barré syndrome associated with multiple IgM anti-ganglioside antibodies. Muscle Nerve 38(6):1630–1633PubMed
45.
go back to reference Umehara F, Kore-Eda Y, Arime T, Kubota R, Arimura K, Osame M (1997) Chronic sensory ataxic neuropathy and ophthalmoplegia with oculomotor nerve hypertrophy associated with IgM antibodies against gangliosides containing disialosyl groups. J Neurol Neurosurg Psychiatry 62(6):673–674PubMedPubMedCentral Umehara F, Kore-Eda Y, Arime T, Kubota R, Arimura K, Osame M (1997) Chronic sensory ataxic neuropathy and ophthalmoplegia with oculomotor nerve hypertrophy associated with IgM antibodies against gangliosides containing disialosyl groups. J Neurol Neurosurg Psychiatry 62(6):673–674PubMedPubMedCentral
Metadata
Title
Sustained response to subcutaneous immunoglobulins in chronic ataxic neuropathy with anti-disialosyl IgM antibodies (CANDA): report of two cases and review of the literature
Authors
D. Marastoni
L. Africa
A. Peretti
S. Bocci
L. Insana
S. Ferrari
F. Ginanneschi
G. Zanette
G. M. Fabrizi
F. Giannini
Publication date
01-08-2020
Publisher
Springer Berlin Heidelberg
Keyword
Lymphoma
Published in
Journal of Neurology / Issue 8/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-020-09843-y

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