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Objective: We sought to determine the prevalence, clinical features, and laboratory characteristics of polyneuropathies in Waldenström's macroglobulinaemia (WM), a malignant bone marrow disorder with lymphocytes that produce monoclonal IgM.Methods: We prospectively studied 119 patients with WM and 58 controls. Medical history was taken, and neurological examinations, electrodiagnostic tests, and serum studies were performed by different examiners who were blinded to results except the diagnosis of WM.Results: Polyneuropathy symptoms, including discomfort and sensory loss in the legs, occurred more frequently (p<0.001) in patients with WM (47%) than in controls (9%). Patients with WM had 35% lower quantitative vibration scores, and more frequent pin loss (3.4 times) and gait disorders (5.5 times) than controls (all p<0.001). Patients with IgM binding to sulphatide (5% of WM) had sensory axon loss; those with IgM binding to myelin associated glycoprotein (MAG) (4% of WM) had sensorimotor axon loss and demyelination. Patients with WM with IgM binding to sulphatide (p<0.005) or MAG (p<0.001) had more severe sensory axon loss than other patients with WM. Demyelination occurred in 4% of patients with WM with no IgM binding to MAG. Age related reductions in vibration sense and sural SNAP amplitudes were similar ( approximately 30%) in WM and controls.Conclusions: Peripheral nerve symptoms and signs occur more frequently in patients with WM than controls, involve sensory modalities, and are often associated with gait disorders. IgM binding to MAG or sulphatide is associated with a further increase in the frequency and severity of peripheral nerve involvement. Age related changes, similar to those in controls, add to the degree of reduced nerve function in patients with WM. [ABSTRACT FROM AUTHOR]

Objectives: Polyneuropathies with associated serum IgM antibodies are often difficult to treat. Rituximab is a monoclonal antibody directed against the B cell surface membrane marker CD20. Rituximab eliminates B cells from the circulation, and, over time, could reduce cells producing autoantibodies. This study tested the ability of rituximab to produce changes in serum antibody titres, and improvement in strength, in patients with neuromuscular disorders and IgM autoantibodies. Methods: Over a period of two years, the authors evaluated changes in strength, measured by quantitative dynamometry, and concentrations of several types of serum antibodies in patients with polyneuropathies and serum IgM autoantibodies. Twenty one patients treated with rituximab were compared with 13 untreated controls. Results: Treatment with rituximab was followed by improved strength (an increase of mean (SEM) 23% (2%) of normal levels of strength), a reduction in serum IgM autoantibodies (to 43% (4%) of initial values), and a reduction in total levels of IgM (to 55% (4%) of initial values). There was no change in levels of serum IgG antibodies. There were no major side effects, even though B cells were virtually eliminated from the circulation for periods up to two years. Conclusions: In patients with IgM autoantibody associated peripheral neuropathies, rituximab treatment is followed by reduced serum concentrations of IgM, but not IgG, antibodies, and by improvement in strength. Additional studies, with placebo controls and blinded outcome measures, are warranted to further test the efficacy of rituximab treatment of IgM associated polyneuropathies. [ABSTRACT FROM AUTHOR]

Objectives: To study myopathies with serum antibodies to the signal recognition particle (SRP), an unusual, myositis specific antibody associated syndrome that has not been well characterised pathologically.Methods: Clinical, laboratory, and myopathological features were evaluated in seven consecutive patients with a myopathy and serum anti-SRP antibodies, identified over three years. The anti-SRP myopathy was compared with myopathology in other types of inflammatory and immune myopathies.Results: The patients with anti-SRP antibodies developed weakness at ages ranging from 32 to 70 years. Onset was seasonal (August to January). Weakness became severe and disability developed rapidly over a period of months. Muscle pain and fatigue were present in some patients. No patient had a dermatomyositis-like rash. Serum creatine kinase was very high (3000 to 25 000 IU/l). Muscle biopsies showed an active myopathy, including muscle fibre necrosis and regeneration. There was prominent endomysial fibrosis, but little or no inflammation. Endomysial capillaries were enlarged, reduced in number, and associated with deposits of the terminal components of complement (C5b-9, membrane attack complex). Strength improved in several patients after corticosteroid treatment.Conclusions: Myopathies associated with anti-SRP antibodies may produce severe and rapidly progressive weakness and disability. Muscle biopsies show active myopathy with pathological changes in endomysial capillaries but little inflammation. Corticosteroid treatment early in the course of the illness is often followed by improvement in strength. In patients with rapidly progressive myopathies and a high serum creatine kinase but little inflammation on muscle biopsy, measurement of anti-SRP antibodies and pathological examination of muscle, including evaluation of endomysial capillaries, may provide useful information on diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate muscle pathology and clinical characteristics in patients with a myopathy and serum antibodies to the Jo-1 antigen (histidyl t-RNA synthetase).Background: Anti-Jo-1 antibodies occur in syndromes that may include muscle weakness and pain, Raynaud's phenomenon, interstitial lung disease, arthritis, and a skin rash different from that seen in dermatomyositis. The muscle pathology is not well defined.Methods: Case series. Review of charts, muscle biopsies, and laboratory records. Features of myopathology in 11 patients with anti-Jo-1 antibody associated myopathies were compared with other types of inflammatory myopathies.Results: Myopathology in patients with anti-Jo-1 antibodies consistently included fragmentation of, and macrophage predominant inflammation in, perimysial connective tissue. Perifascicular myopathic changes, including atrophy, regenerating muscle fibres, and some muscle fibre necrosis, were most common in regions near the connective tissue pathology and were most prominent in patients with more severe weakness. Unlike many other inflammatory myopathies, inflammation in endomysial and perivascular regions was uncommon. By contrast with dermatomyositis, capillary density was normal.Conclusions: Myopathological changes in the anti-Jo-1 antibody syndrome include perimysial connective tissue fragmentation and inflammation, with muscle fibre pathology in neighbouring perifascicular regions. Myositis with anti-Jo-1 antibodies may result from an immune mediated disorder of connective tissue. [ABSTRACT FROM AUTHOR]

The fundamental abnormality affecting the neuromuscular junctions of myasthenic patients is a reduction of available AChRs, due to an autoimmune attack directed against the receptors. Antibodies to AChR are present in most patients, and there is evidence that they have a predominant pathogenic role in the disease, aided by complement. The mechanism of antibody action involves acceleration of the rate of degradation of AChRs, attributable to cross-linking of the receptors. In addition, antibodies may block AChRs, and may participate in producing destructive changes, perhaps in conjunction with complement. The possibility that cell-mediated mechanisms may play a role in the autoimmune responses of some myasthenic patients remains to be explored. Although the target of the autoimmune attack in myasthenic patients is probably always the acetylcholine receptors, it is not yet clear which of these immune mechanisms are most important. It is likely that the relative role of each mechanism varies from patient to patient. One of the goals of future research will be to identify the relative importance of each of these mechanisms in the individual patient, and to tailor specific immunotherapeutic measures to the abnormalities found. [ABSTRACT FROM AUTHOR]