Research Article| Volume 345, ISSUE 1-2, P224-227, October 15, 2014

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Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy

Published:August 02, 2014DOI:


      • Peripheral neuropathy with anti-MAG monoclonal IgM may be improved by Rituximab.
      • Acute worsening after Rituximab has been reported in 10 cases including our 3 patients.
      • It may occur even in patients who have already received Rituximab without problem.
      • It is unpredictable and severe and recovery may not be complete.
      • This should be considered in making treatment decision.



      Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody.


      We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases.


      Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction.


      Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months.


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        • Rajabally Y.A.
        Neuropathy and paraproteins: review of a complex association.
        Eur J Neurol. 2011; 18: 1291-1298
        • Nobile-Orazio E.
        Update on neuropathies associated with monoclonal gammopathy of undetermined significance (2008–2010).
        J Peripher Nerv Syst. 2010; 15: 302-306
        • Steck A.J.
        • Stalder A.K.
        • Renaud S.
        Anti-myelin-associated glycoprotein neuropathy.
        Curr Opin Neurol. 2006; 19: 458-463
        • Benedetti L.
        • Briani C.
        • Grandis M.
        • Vigo T.
        • Gobbi M.
        • Ghiglione E.
        • et al.
        Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M.
        Journal of the peripheral nervous system: JPNS. 2007; 12: 102-107
        • Kilidireas C.
        • Anagnostopoulos A.
        • Karandreas N.
        • Mouselimi L.
        • Dimopoulos M.A.
        Rituximab therapy in monoclonal IgM-related neuropathies.
        Leuk Lymphoma. 2006; 47: 859-864
        • Levine T.D.
        • Pestronk A.
        IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using Rituximab.
        Neurology. 1999; 52: 1701-1704
        • Gorson K.C.
        • Natarajan N.
        • Ropper A.H.
        • Weinstein R.
        Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial.
        Muscle Nerve. 2007; 35: 66-69
        • Dalakas M.C.
        • Rakocevic G.
        • Salajegheh M.
        • Dambrosia J.M.
        • Hahn A.F.
        • Raju R.
        • et al.
        Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy.
        Ann Neurol. 2009; 65: 286-293
        • Leger J.M.
        • Viala K.
        • Nicolas G.
        • Creange A.
        • Vallat J.M.
        • Pouget J.
        • et al.
        Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy.
        Neurology. 2013; 80: 2217-2225
        • Gironi M.
        • Saresella M.
        • Ceresa L.
        • Calvo M.
        • Ferrante P.
        • Merli F.
        • et al.
        Clinical and immunological worsening in a patient affected with Waldenstrom macroglobulinemia and anti-mag neuropathy after treatment with rituximab.
        Haematologica. 2006; 91: ECR17
        • Rojas-Garcia R.
        • Gallardo E.
        • de Andres I.
        • de Luna N.
        • Juarez C.
        • Sanchez P.
        • et al.
        Chronic neuropathy with IgM anti-ganglioside antibodies: lack of long term response to rituximab.
        Neurology. 2003; 61: 1814-1816
        • Stork A.C.
        • Notermans N.C.
        • Vrancken A.F.
        • Cornblath D.R.
        • van der Pol W.L.
        Rapid worsening of IgM anti-MAG demyelinating polyneuropathy during rituximab treatment.
        Journal of the peripheral nervous system: JPNS. 2013; 18: 189-191
        • Broglio L.
        • Lauria G.
        Worsening after rituximab treatment in anti-mag neuropathy.
        Muscle Nerve. 2005; 32: 378-379
        • Hughes R.
        • Bensa S.
        • Willison H.
        • Van den Bergh P.
        • Comi G.
        • Illa I.
        • et al.
        Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.
        Ann Neurol. 2001; 50: 195-201
        • Pestronk A.
        • Florence J.
        • Miller T.
        • Choksi R.
        • Al-Lozi M.T.
        • Levine T.D.
        Treatment of IgM antibody associated polyneuropathies using rituximab.
        J Neurol Neurosurg Psychiatry. 2003; 74: 485-489
        • Benedetti L.
        • Franciotta D.
        • Vigo T.
        • Grandis M.
        • Fiorina E.
        • Ghiglione E.
        • et al.
        Relapses after treatment with rituximab in a patient with multiple sclerosis and anti myelin-associated glycoprotein polyneuropathy.
        Arch Neurol. 2007; 64: 1531-1533
        • Noronha V.
        • Fynan T.M.
        • Duffy T.
        Flare in neuropathy following rituximab therapy for Waldenstrom's macroglobulinemia.
        J Clin Oncol. 2006; 24: e3
        • Yang B.
        • Lu X.C.
        • Yu R.L.
        • Chi X.H.
        • Zhang W.Y.
        • Zhu H.L.
        • et al.
        Diagnosis and treatment of rituximab-induced acute tumor lysis syndrome in patients with diffuse large B-cell lymphoma.
        Am J Med Sci. 2012; 343: 337-341
        • Valldeoriola F.
        • Graus F.
        • Steck A.J.
        • Munoz E.
        • de la Fuente M.
        • Gallart T.
        • et al.
        Delayed appearance of anti-myelin-associated glycoprotein antibodies in a patient with chronic demyelinating polyneuropathy.
        Ann Neurol. 1993; 34: 394-396
        • Dalakas M.C.
        Invited article: inhibition of B cell functions: implications for neurology.
        Neurology. 2008; 70: 2252-2260