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Are Miller Fisher syndrome and CANDA due to a paranodopathy?

  • Jean-Michel Vallat
    Affiliations
    Department of Neurology, National Reference Center for ‘Rare Peripheral Neuropathies’, University Hospital of Limoges (CHU Limoges - Dupuytren Hospital), 2 avenue Martin Luther King, 87042 Limoges, France
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  • Nathalie Deschamps
    Affiliations
    Department of Neurology, National Reference Center for ‘Rare Peripheral Neuropathies’, University Hospital of Limoges (CHU Limoges - Dupuytren Hospital), 2 avenue Martin Luther King, 87042 Limoges, France
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  • Frédéric Taithe
    Affiliations
    Department of Neurology, University Hospital of Clermont-Ferrand (CHU Clermont-Ferrand - Gabriel Montpied Hospital), 63003 Clermont-Ferrand, FT, France
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  • Laurence Richard
    Affiliations
    Department of Neurology, National Reference Center for ‘Rare Peripheral Neuropathies’, University Hospital of Limoges (CHU Limoges - Dupuytren Hospital), 2 avenue Martin Luther King, 87042 Limoges, France
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  • Mathilde Duchesne
    Affiliations
    Department of Neurology, National Reference Center for ‘Rare Peripheral Neuropathies’, University Hospital of Limoges (CHU Limoges - Dupuytren Hospital), 2 avenue Martin Luther King, 87042 Limoges, France

    Department of pathology, University Hospital of Limoges (CHU Limoges - Dupuytren Hospital), 2 avenue Martin Luther King, 87042 Limoges, France
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  • Laurent Magy
    Affiliations
    Department of Neurology, National Reference Center for ‘Rare Peripheral Neuropathies’, University Hospital of Limoges (CHU Limoges - Dupuytren Hospital), 2 avenue Martin Luther King, 87042 Limoges, France
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  • Stéphane Mathis
    Correspondence
    Corresponding author.
    Affiliations
    Department of Neurology, Nerve-Muscle Unit, AOC National Reference Center for Neuromuscular Disorders, ALS Center, University Hospital of Bordeaux (CHU Bordeaux - Pellegrin Hospital), Place Amélie Raba-Léon, 33000 Bordeaux, SM, France
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      Highlights

      • Electron microscopic observations suggest that both patients present lesions in favor of a paranodopathy.
      • Some paranodes seem to be associated with macrophages.
      • These lesions are in favor of a complement-mediated dysfunction/disruption of the nodal region.
      • This may be due to antibodies against gangliosides which are mainly located at the level of the paranode (axolemma).
      • Miller Fisher syndrome and CANDA should be classified as paranodopathies.

      Abstract

      Objective

      To study the pathological characteristics of acute and chronic ataxic peripheral neuropathy at the level of the node of Ranvier.

      Study design and setting

      We performed the pathological study (nerve biopsy of a sural nerve) of two patients, one with an acute form of ataxic peripheral neuropathy called ‘Miller Fisher syndrome’ (MFS), the other one with a chronic form called ‘chronic ataxic neuropathies with disialosyl antibodies’ (CANDA).

      Results

      A dysimmune process involving peripheral nerves commences in myelin, at the internodal area or/and in the paranodal and nodal regions. Our electron microscopic observations suggest that both patients present lesions in favor of a paranodopathy.

      Conclusion

      Many of the immune-mediated peripheral neuropathies are now classified as nodoparanodopathies. This subtype of auto-immune neuropathy may present various clinical phenotypes such as ‘Acute Motor Axonal Neuropathy’ (AMAN), ‘Acute Motor and Sensory Neuropathy’ (AMSAN) or ‘chronic inflammatory demyelinating polyradiculoneuropathy’ (CIDP), and are associated with anti-disialosyl antibodies. In our two cases, some paranodes seem to be associated with macrophages and we hypothesized that these lesions are in favor of a complement-mediated dysfunction/disruption of the nodal region due to disialosyl antibodies against gangliosides which are mainly located at the level of the axolemma of the paranode.

      Keywords

      Abbreviations:

      AIDP (acute inflammatory demyelinating polyradiculoneuropathy), AMAN (Acute Motor Axonal Neuropathy), AMSAN (Acute Motor and Sensory Neuropathy), CANDA (chronic ataxic neuropathies with disialosyl antibodies), CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein), CIDP (chronic inflammatory demyelinating polyradiculoneuropathy), EM (electron microscopy), ENMG (electroneuromyogram), GBS (Guillain-Barré syndrome), IV (index value), MAC (membrane attack complex), MFS (Miller Fisher syndrome), MGUS (Monoclonal Gammopathy of Undetermined Significance)
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      References

        • Yuki N.
        • Uncini A.
        Acute and chronic ataxic neuropathies with disialosyl antibodies: a continuous clinical spectrum and a common pathophysiological mechanism.
        Muscle Nerve. 2014; 49: 629-635
        • Vallat J.M.
        • Magy L.
        • Corcia P.
        • Boulesteix J.M.
        • Uncini A.
        • Mathis S.
        Ultrastructural lesions of nodo-paranodopathies in peripheral neuropathies.
        J. Neuropathol. Exp. Neurol. 2020; 79: 247-255
        • Van den Bergh P.Y.K.
        • van Doorn P.A.
        • Hadden R.D.M.
        • Avau B.
        • Vankrunkelsven P.
        • Allen J.A.
        • Attarian S.
        • Blomkwist-Markens P.H.
        • Cornblath D.R.
        • Eftimov F.
        • Goedee H.S.
        • Harbo T.
        • Kuwabara S.
        • Lewis R.A.
        • Lunn M.P.
        • Nobile-Orazio E.
        • Querol L.
        • Rajabally Y.A.
        • Sommer C.
        • Topaloglu H.A.
        European academy of neurology/peripheral nerve society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force-second revision.
        Eur. J. Neurol. 2021; 28: 3556-3583
        • Devaux J.J.
        • Odaka M.
        • Yuki N.
        Nodal proteins are target antigens in Guillain-Barré syndrome.
        J. Peripher. Nerv. Syst. 2012; 17: 62-71
        • Bilbao J.M.
        • Schmidt R.E.
        Quantitative techniques.
        in: Bilbao J.M. Schmidt R.E. Biopsy Diagnosis of Peripheral Neuropathy. Springer, New York2014: 43-50
        • Fisher M.
        An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia).
        N. Engl. J. Med. 1956; 255: 57-65
        • Ilyas A.A.
        • Quarles R.H.
        • Dalakas M.C.
        • Brady R.O.
        Polyneuropathy with monoclonal gammopathy: glycolipids are frequently antigens for IgM paraproteins.
        Proc. Natl. Acad. Sci. U. S. A. 1985; 82: 6697-6700
        • Mierzwa A.J.
        • Arevalo J.C.
        • Schiff R.
        • Chao M.V.
        • Rosenbluth J.
        Role of transverse bands in maintaining paranodal structure and axolemmal domain organization in myelinated nerve fibers: effect on longevity in dysmyelinated mutant mice.
        J. Comp. Neurol. 2010; 518: 2841-2853
        • Serrano-Munuera C.
        • Gallardo E.
        • Rojas R.
        • De Luna N.
        • Gonzalez-Masegosa A.
        • Marti-Masso J.F.
        • Martinez-Matos A.
        • Ortiz N.
        • Rene R.
        • Berciano J.
        • Grau J.M.
        • Willison H.J.
        • Graus F.
        • Illa I.
        Antiganglioside antibodies in acute self-limiting ataxic neuropathy: incidence and significance.
        J. Neuroimmunol. 2001; 120: 78-83
        • Kuwabara S.
        • Asahina M.
        • Nakajima M.
        • Mori M.
        • Fukutake T.
        • Hattori T.
        • Yuki N.
        Special sensory ataxia in Miller Fisher syndrome detected by postural body sway analysis.
        Ann. Neurol. 1999; 45: 533-536
        • Miller J.A.
        • Spyropoulos A.
        • Jaros E.
        • Galban-Horcajo F.
        • Whittaker R.G.
        • Willison H.J.
        Anti-GQ1b ganglioside positive Miller Fisher syndrome - evidence of paranodal pathology on nerve biopsy.
        J. Neuromuscul. Dis. 2014; 1: 191-195
        • Vallat J.M.
        • Mathis S.
        • Vegezzi E.
        • Richard L.
        • Duchesne M.
        • Gallouedec G.
        • Corcia P.
        • Magy L.
        • Uncini A.
        • Devaux J.
        Antibody- and macrophage-mediated segmental demyelination in chronic inflammatory demyelinating polyneuropathy: clinical, electrophysiological, immunological and pathological correlates.
        Eur. J. Neurol. 2020; 27: 692-701
        • Chiba A.
        • Kusunoki S.
        • Shimizu T.
        • Kanazawa I.
        Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome.
        Ann. Neurol. 1992; 31: 677-679
        • Susuki K.
        • Rasband M.N.
        • Tohyama K.
        • Koibuchi K.
        • Okamoto S.
        • Funakoshi K.
        • Hirata K.
        • Baba H.
        • Yuki N.
        Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers.
        J. Neurosci. 2007; 27: 3956-3967
        • Sheikh K.A.
        • Deerinck T.J.
        • Ellisman M.H.
        • Griffin J.W.
        The distribution of ganglioside-like moieties in peripheral nerves.
        Brain. 1999; 122: 449-460
        • Susuki K.
        • Baba H.
        • Tohyama K.
        • Kanai K.
        • Kuwabara S.
        • Hirata K.
        • Furukawa K.
        • Rasband M.N.
        • Yuki N.
        Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers.
        Glia. 2007; 55: 746-757
        • Kusunoki S.
        • Willison H.J.
        • Jacobs B.C.
        Antiglycolipid antibodies in Guillain-Barré and Fisher syndromes: discovery, current status and future perspective.
        J. Neurol. Neurosurg. Psychiatry. 2021; 92: 311-318
        • Uncini A.
        • Mathis S.
        • Vallat J.M.
        New classification of autoimmune neuropathies based on target antigens and involved domains of myelinated fibres.
        J. Neurol. Neurosurg. Psychiatry. 2021; 93: 57-67
        • Koga M.
        • Gilbert M.
        • Li J.
        • Koike S.
        • Takahashi M.
        • Furukawa K.
        • Hirata K.
        • Yuki N.
        Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry.
        Neurology. 2005; 64: 1605-1611
        • Willison H.J.
        • O’Leary C.P.
        • Veitch J.
        • Blumhardt L.D.
        • Busby M.
        • Donaghy M.
        • Fuhr P.
        • Ford H.
        • Hahn A.
        • Renaud S.
        • Katifi H.A.
        • Ponsford S.
        • Reuber M.
        • Steck A.
        • Sutton I.
        • Schady W.
        • Thomas P.K.
        • Thompson A.J.
        • Vallat J.M.
        • Winer J.
        The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies.
        Brain. 2001; 124: 1968-1977
        • Vallat J.M.
        • Nizon M.
        • Magee A.
        • Isidor B.
        • Magy L.
        • Péréon Y.
        • Richard L.
        • Ouvrier R.
        • Cogné B.
        • Devaux J.
        • Zuchner S.
        • Mathis S.
        Contactin-associated protein 1 (CNTNAP1) mutations induce characteristic lesions of the Paranodal region.
        J. Neuropathol. Exp. Neurol. 2016; 75: 1155-1159
        • Vallat J.M.
        • Yuki N.
        • Sekiguchi K.
        • Kokubun N.
        • Oka N.
        • Mathis S.
        • Magy L.
        • Sherman D.L.
        • Brophy P.J.
        • Devaux J.J.
        Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-Neurofascin 155 antibodies.
        Neuromuscul. Disord. 2017; 27: 290-293
        • Susuki K.
        • Yuki N.
        • Schafer D.P.
        • Hirata K.
        • Zhang G.
        • Funakoshi K.
        • Rasband M.N.
        Dysfunction of nodes of Ranvier: a mechanism for anti-ganglioside antibody-mediated neuropathies.
        Exp. Neurol. 2012; 233: 534-542
        • Hafer-Macko C.
        • Hsieh S.T.
        • Li C.Y.
        • Ho T.W.
        • Sheikh K.
        • Cornblath D.R.
        • McKhann G.M.
        • Asbury A.K.
        • Griffin J.W.
        Acute motor axonal neuropathy: an antibody-mediated attack on axolemma.
        Ann. Neurol. 1996; 40: 635-644
        • Koike H.
        • Kadoya M.
        • Kaida K.I.
        • Ikeda S.
        • Kawagashira Y.
        • Iijima M.
        • Kato D.
        • Ogata H.
        • Yamasaki R.
        • Matsukawa N.
        • Kira J.I.
        • Katsuno M.
        • Sobue G.
        Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies.
        J. Neurol. Neurosurg. Psychiatry. 2017; 88: 465-473
        • Uncini A.
        • Santoro L.
        Reply to “nodal conduction block and reversible conduction failure are not electrophysiological markers for axonal loss”.
        Clin. Neurophysiol. 2021; 132: 2934-2935
        • Liu J.X.
        • Willison H.J.
        • Pedrosa-Domellof F.
        Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles.
        Invest. Ophthalmol. Vis. Sci. 2009; 50: 3226-3232
        • Kusunoki S.
        • Chiba A.
        • Kanazawa I.
        Anti-GQ1b IgG antibody is associated with ataxia as well as ophthalmoplegia.
        Muscle Nerve. 1999; 22: 1071-1074