Inflammatory Demyelinating Neuropathies and Neuropathies Associated with Monoclonal Gammopathies: Treatment Update

Steck, Andreas; Czapliński, Adam; Renaud, Susanne

doi:10.1016/j.nurt.2008.08.012

Cited by 18 publications

(7 citation statements)

References 81 publications

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“…Chlorambucil and prednisone, a combination used to treat Waldenström’s macroglobulinemia, can improve or stabilize a small number of patients, as we have witnessed in one, 43 but the benefit is minimal and does not often outweigh the risks. 37 – 42 …”

Section: Treatmentmentioning

confidence: 99%

“…33 Since the IgM-anti-MAG antibodies appear to exert a pathogenic effect on the myelin structure and function, 34,35 it was expected that suppressing their production, removal of the antibodies or modification of the immune network should have a therapeutic effect. Unfortunately, this is not the case in clinical practice because conventional immunotherapies and chemotherapies offer marginal or transient benefit, 26,27,[35][36][37][38][39][40][41][42] necessitating the need for more specific therapies.…”

Section: Treatmentmentioning

confidence: 99%

“…If, however, manifest gait ataxia, falls and muscle weakness, or present with a CIDPlike picture from the outset, they should be treated early before permanent deficits due to axonal degeneration take place. [36][37][38][39][40][41][42]…”

Section: When To Initiate Therapymentioning

confidence: 99%

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Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies

Dalakas

2018

Ther Adv Neurol Disord

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Polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy is the most common paraproteinemic neuropathy, comprising a clinicopathologically and immunologically distinct entity. The clinical spectrum spans from distal paresthesias and mild gait imbalance to more severe sensory ataxia, with falls and a varying degree of distal sensorimotor deficits. In approximately 75% of patients, the monoclonal IgM immunoreacts with myelin-associated glycoprotein (MAG) and sulfoglucuronyl glycosphingolipid (SGPG), or other peripheral nerve glycolipids that serve as antigens. These antibodies are considered pathogenic because IgM and complement are deposited on the myelin sheath, splitting the myelin lamellae, while adoptive transfer of patients’ IgM into susceptible host animals causes sensory ataxia and reproduces the human pathology. In spite of the apparently convincing pathogenicity of these antibodies, the response to immunotherapies remains suboptimal. Clorambuscil, cladibrine, cyclophospamide and intravenous immunoglobulin may help some patients but the benefits are minimal and transient. Open-label studies in >200 patients indicate that rituximab is helpful in 30–50% of these patients, even with long-term benefits, probably by suppressing IgM anti-MAG antibodies or inducing immunoregulatory T cells. Two controlled studies with rituximab did not however meet the primary endpoint, mostly because of the poor sensitivity of the scales used; they did however show statistical improvement in secondary endpoints and improved clinical functions in several patients. This review provides an overview of the clinical phenotypes and immunoreactivity of IgM to glycolipids or glycoproteins of peripheral nerve myelin, summarizes the progress on treatment with rituximab as a promising therapy, discusses the pitfalls of scales used, identifies possible biomarkers of response to therapy and highlights the promising new anti-B cell or target-specific immunotherapies.

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Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies

Dalakas

2018

Ther Adv Neurol Disord

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“…The majority of MMN patients respond to IVIg therapy but require frequent infusions to maintain stability. Some patients however respond less well and continue to have significant disability [Steck et al 2008].…”

Section: Peripheral Neuropathiesmentioning

confidence: 99%

Practical considerations on the use of rituximab in autoimmune neurological disorders

Kosmidis

Dalakas

2010

Ther Adv Neurol Disord

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Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic's disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity.

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“…In both cases, the course of the neuropathy may become independent of the myeloma. Osteosclerotic myeloma is often associated with a symmetrical, distal sensorimotor neuropathy with predominant motor symptoms that resemble CIDP, or with additional symptoms indicative of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) [84,85]. Patients often have one or just a few osteosclerotic lesions that tend to involve the spine and proximal long bones.…”

Section: Subacute Sensory Neuronopathymentioning

confidence: 99%

Update on Paraneoplastic Neurologic Disorders

Rosenfeld

Dalmau

2010

The Oncologist

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After completing this course, the reader will be able to:1. Identify the symptoms of paraneoplastic neurologic disorders (PNDs) and, when appropriate, include PNDs in the differential diagnosis when evaluating patients with systemic cancers.2. Describe the relationship of paraneoplastic antibodies and specific syndromes, where present, and their use in diagnosis of PND.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTWhen patients with cancer develop neurologic symptoms, common causes include metastasis, infections, coagulopathy, metabolic or nutritional disturbances, and neurotoxicity from treatments. A thorough clinical history, temporal association with cancer therapies, and results of ancillary tests usually reveal one of these mechanisms as the etiology. When no etiology is identified, the diagnosis considered is often that of a paraneoplastic neurologic disorder (PND). With the recognition that PNDs are more frequent than previously thought, the availability of diagnostic tests, and the fact that, for some PNDs, treatment helps, PNDs should no longer be considered diagnostic zebras, and when appropriate should be included in the differential diagnosis early in the evaluation. The Oncologist 2010;15:603-617

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Inflammatory Demyelinating Neuropathies and Neuropathies Associated with Monoclonal Gammopathies: Treatment Update

Cited by 18 publications

References 81 publications

Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies

Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies

Practical considerations on the use of rituximab in autoimmune neurological disorders

Update on Paraneoplastic Neurologic Disorders

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