anti-MAG neuropathy

AIM: Neuropathy is a frequent complication of Waldenström's macroglobulinemia (WM), the most common being a demyelinating polyneuropathy with anti-myelin associated glycoprotein (MAG) antibodies, but also cryoglobulins, vasculitis, neurolymphomatosis, and amyloidosis. We describe a patient with IgM/kappa WM who presented with a severe, not length-dependent, peripheral neuropathy as clinical onset of IgM/kappa-related amyloidosis. METHODS: A 69-year-old woman came to our attention for weight loss, gait imbalance and sensory loss at upper limbs...

BACKGROUND AND OBJECTIVES: Deposition of myelin-associated glycoprotein (MAG) immunoglobulin M (IgM) antibodies in the sural nerve is a key feature in anti-MAG neuropathy. Whether the blood-nerve barrier (BNB) is disrupted in anti-MAG neuropathy remains elusive.We aimed to evaluate the effect of sera from anti-MAG neuropathy at the molecular level using our in vitro human BNB model and observe the change of BNB endothelial cells in the sural nerve of anti-MAG neuropathy. METHODS: Diluted sera from patients with anti-MAG neuropathy (n = 16), monoclonal gammopathies of undetermined significance (MGUS) neuropathy (n = 7), amyotrophic lateral sclerosis (ALS, n = 10), and healthy controls (HCs, n = 10) incubated with human BNB endothelial cells to identify the key molecule of BNB activation using RNA-seq and a high-content imaging system, and exposed with a BNB coculture model to evaluate small molecule/IgG/IgM/anti-MAG antibody permeability...

Chronic dysimmune neuropathies encompass a group of neuropathies that share immune-mediated pathomechanism. Chronic dysimmune antibody-related neuropathies include anti-MAG neuropathy, multifocal motor neuropathy, and neuropathies related to immune attack against paranodal antigens. Such neuropathies exhibit distinguishing pathomechanism, clinical and response to therapy features with respect to chronic inflammatory demyelinating polyradiculoneuropathy and its variants, which represent the most frequent form of chronic dysimmune neuropathy...

Neuropathy with anti-myelin-associated glycoprotein (MAG) antibodies commonly demonstrates distal-dominant prolongation of nerve conduction. However, recent electrophysiological studies have shown that distal motor demyelination is not always a distinct feature. We aimed to elucidate whether the longitudinal progression of nerve impairment occurs in a distal-dominant manner. Seven patients with neuropathy with anti-MAG antibodies were enrolled. Sequential nerve conduction studies revealed nerve conduction reduction only at the wrist segment in the median nerve of the patients, but not in the ulnar nerve...

BACKGROUND: The safety of the new vaccines against SARS-CoV-2 have already been shown, although data on patients with polyneuropathy are still lacking. The aim of this study is to evaluate the adherence to SARS-CoV-2 vaccination, as well as the reactogenicity to those vaccines in patients affected by neuropathy. METHODS: A multicentric and web-based cross-sectional survey was conducted among patients affected by neuropathy from part of South Italy. RESULTS: Out of 285 responders, n = 268 were included in the final analysis and n = 258 of them (96...

BACKGROUND: Anti-myelin-associated-glycoprotein (MAG) neuropathy is a distal, predominantly demyelinating, sensory or sensory-motor polyneuropathy most often developing in the context of an IgM-type monoclonal gammopathy due to monoclonal gammopathy of undetermined significance or lymphoplasmacytic lymphoma. Rituximab is considered standard therapy for treatment naïve patients, but optimal treatment methods for relapsed/refractory patients have not been established. CASE PRESENTATION: We demonstrate that tirabrutinib, a second-generation Burton kinase inhibitor, led to drastic improvements of polyneuropathy that were affirmed by nerve conduction studies in a rituximab-refractory anti-MAG neuropathy patient...

Waldenström's disease is a B-cell neoplasm characterized by the accumulation of lymphoplasmacytic cells (LPCs) in the bone marrow, and more rarely in the lymph nodes and the spleen, which produce a monoclonal immunoglobulin M (IgM) protein. The diagnosis requires the identification of LPCs in the bone marrow, using specific markers in flow cytometry. The MYD88L265P mutation is found in 95% of cases and the CXCR4 mutation in 30-40% of cases. These markers must be sought because they have a diagnostic and prognostic role, and they might become predictive in the future...

BACKGROUND AND PURPOSE: We evaluated the clinical and neurophysiological efficacy of rituximab (RTX) in a neurophysiologically homogeneous group of patients with monoclonal gammopathy and immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody (anti-MAG) demyelinating polyneuropathy. METHODS: Twenty three anti-MAG-positive polyneuropathic patients were prospectively evaluated before and for 2 years after treatment with RTX 375 mg/m2 . The Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (INCAT-ds), modified INCAT sensory score (mISS), Medical Research Council sum score, Patients' Global Impression of Change scale were used, IgM levels were assessed and extensive electrophysiological examinations were performed before (T0) and 1 year (T1) and 2 years (T2) after RTX treatment...

OBJECTIVES: Ibrutinib is active in anti-myelin-associated glycoprotein (MAG) polyneuropathy with MYD88L265P mutation; however, its efficacy is likely to be low in MYD88 wild-type patients. Venetoclax, an oral inhibitor of BCL2, in combination with rituximab is highly active in ibrutinib-resistant hematologic malignancies. We report on the first patient with anti-MAG polyneuropathy and MYD88 wild-type who responded to venetoclax-rituximab. METHODS: A 62-year-old woman with chronic lymphocytic leukemia had IgM/K anti-MAG neuropathy...

It is well recognized that B-cell clonal disorders such as Waldenstrom's macroglobulinaemia may affect the central nervous system by direct infiltration of malignant B cells (Bing-Neel syndrome). However, there is no recognition in the current literature of a clear link between paraproteinaemia and primary brain tumours such as glioma. We present 3 cases of classical IgM paraproteinaemic neuropathy who developed glioblastoma in the course of their illness following treatment with chemoimmunotherapy (CIT). Due to the progressive symptomatic nature of their neuropathy, all 3 patients were treated with CIT...

Chronic immune mediated neuropathy is a heterogenous group of peripheral nerve diseases, encompassing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), autoimmune nodopathy, multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) neuropathy. Rituximab (RTX) is a chimeric monoclonal antibody targeting the CD20 antigen, which has been used in the treatment of autoimmune neuropathies, although the efficacy of RTX remains unclear. A literature search was performed using Medline, Embase and Cochrane Register for studies between 2000 and 2021 using the search terms "Chronic inflammatory demyelinating polyneuropathy" OR "Multifocal motor neuropathy" OR "Myelin associated glycoprotein" OR "Distal acquired demyelinating neuropathy" OR "Multifocal acquired demyelinating sensory and motor neuropathy" OR "demyelinating neuropathy" AND "Rituximab"...

We report the case of a patient with a very severe predominantly demyelinating sensorimotor polyneuropathy (with axonal loss) that had developed over several months, along with an immunoglobulin-M monoclonal gammopathy without anti-myelin associated glycoprotein antibodies (or other antibodies against myelin). Widening of myelin lamellae were frequently observed by electron microscopic examination of a nerve biopsy: immunoglobulin-M targeting an unknown myelin antigen appears to be responsible for the nerve lesions similar to those observed in anti-myelin associated glycoprotein polyneuropathy...

OBJECTIVES: Ibrutinib is active in anti-myelin-associated glycoprotein (MAG) polyneuropathy with MYD88L265P mutation; however, its efficacy is likely to be low in MYD88 wild-type patients. Venetoclax, an oral inhibitor of BCL2, in combination with rituximab is highly active in ibrutinib-resistant hematologic malignancies. We report on the first patient with anti-MAG polyneuropathy and MYD88 wild-type who responded to venetoclax-rituximab. METHODS: A 62-year-old woman with chronic lymphocytic leukemia had IgM/K anti-MAG neuropathy...

INTRODUCTION: A significant number of patients with a peripheral neuropathy have IgM monoclonal gammopathy (IgM-MG). In this work, we encompassed the spectrum and outcome of IgM-related neuropathies (IgM-NP) in a large monocentric cohort of patients with IgM-MG. METHODS: We retrospectively reviewed the neurological and hematological findings and the course of neuropathy in all patients with IgM-MG over a five-year period in our center (Henri Mondor hospital, Assistance Publique Hôpitaux de Paris (APHP), France)...

Monoclonal immunoglobulin M (IgM) anti-myelin-associated glycoprotein (MAG) neuropathy is a rare disabling condition, most commonly treated with rituximab monotherapy (R), which leads to neurological improvement in only 30%-50% of patients. The combination of rituximab plus chemotherapy has been proven to improve the level of responses. We studied the outcomes of anti-MAG neuropathy patients treated either by R, or by immunochemotherapy (ICT) in our centre, focusing on the incidence of the first neurological response evaluated by the modified Rankin scale (mRS)...

INTRODUCTION/AIMS: Immunoglobulin M neuropathy associated with anti-myelin-associated glycoprotein antibody (IgM/anti-MAG) neuropathy typically presents with chronic, distal-dominant symmetrical sensory or sensorimotor deficits. Ultrasonographic studies of IgM/anti-MAG neuropathy are limited, and were all performed on Western populations. We aimed to characterize the nerve ultrasonographic features of IgM/anti-MAG neuropathy in the Japanese population and evaluate whether they differ from the findings of the common subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP)...

Autoimmune diseases of the peripheral nervous system have so far been treated mainly with exogenous high-dose intravenous immunoglobulins (IVIg), that act through several mechanisms, including neutralization of pathogenic autoantibodies, modulation of lymphocyte activity, interference with antigen presentation, and interaction with Fc receptors, cytokines, and the complement system. Other therapeutic strategies have recently been developed, in part to address the increasing shortage of IVIg, prime among which is the use of B cell depleting monoclonal antibodies, or small molecule inhibitors targeting the B-cell specific kinases...

Monoclonal gammopathy and peripheral neuropathy are common diseases of elderly patients, and almost 10% of patients with neuropathy of unknown cause have paraprotein. However, growing evidence suggests that several hematological malignancies synthesize and release monoclonal proteins that damage the peripheral nervous system through different mechanisms. The spectrum of the disease varies from mild to rapidly progressive symptoms, sometimes affecting not only sensory nerve fibers, but also motor and autonomic fibers...

INTRODUCTION/AIMS: Among subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP), different immune pathophysiologies have been proposed. In this study, sensory nerve conduction studies were compared among clinical subtypes to attempt to better understand the underlying pathophysiology. METHODS: A total of 138 patients with CIDP was classified into clinical subtypes: typical CIDP (N = 68), multifocal CIDP (N = 27), or other (N = 2). Patients with immunoglobulin M (IgM) neuropathy anti-myelin-associated glycoprotein neuropathy (MAG; N = 19) were also included as disease controls...

BACKGROUND AND OBJECTIVES: The objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with clinical response to immunotherapy in patients with anti-MAG neuropathy. METHODS: As of January 29, 2020, we used anti-myelin-associated glycoprotein-related search strings in the Medline database to identify studies that provided information on anti-MAG immunoglobulin M (IgM) autoantibodies and clinical outcomes during immunotherapies...