Amanda C. Guidon

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.

Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.

Objective: To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). Methods: In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell–activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures. Results: As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages of B10 cells. In addition, we observed an increase in MuSK antibody levels with more severe disease. Conclusions: We found prominent B-cell pathology in the distinct form of MG with MuSK autoantibodies. Increased BAFF levels have been described in other autoimmune diseases, including acetylcholine receptor antibody–positive MG. This finding suggests a role for BAFF in the survival of B cells in MuSK MG, which has important therapeutic implications. B10 cells, a recently described rare regulatory B-cell subset that potently blocks Th1 and Th17 responses, were reduced, which suggests a potential mechanism for the breakdown in immune tolerance in patients with MuSK MG.

A Retrospective study of complications of therapeutic plasma exchange in myasthenia

Venous access for therapeutic plasma exchange (TPE) in myasthenia gravis (MG) can be achieved by central venous catheters (CVC) or peripheral veins (PV), and the preferred method varies among providers. We evaluated our institutional experience with TPE venous access method and complications.

Comment: A growing role for nerve ultrasound in diagnosis and management of CIDP?

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated polyneuropathy characterized by segmental demyelination, sometimes accompanied by axonal loss. Nerve size and architecture are altered. Despite composite criteria, diagnosis can be challenging. Furthermore, objective measurements to follow disease activity are limited. High-resolution nerve ultrasound could potentially aid in diagnosis and disease monitoring; it is inexpensive, widely available, noninvasive, and can rapidly image long segments of multiple nerves. However, few studies have examined the relationship between nerve morphology and function in CIDP using ultrasound.1

Peripheral neuropathies in pregnancy.

Purpose of ReviewThis article provides an overview of the most common peripheral neuropathic disorders in pregnancy with a focus on clinical recognition, diagnosis, and treatment. Recent FindingsThe literature on this topic consists primarily of case reports, case series, and retrospective reviews. Recent work, particularly in carpal tunnel syndrome, brachial neuritis, and inherited neuropathies in pregnancy, has added to our knowledge of this field. Awareness of diabetic polyneuropathy with associated autonomic dysfunction in pregnancy has grown as the incidence of diabetes mellitus increases in women of childbearing age. SummaryWomen may develop mononeuropathy, plexopathy, radiculopathy, or polyneuropathy during pregnancy or postpartum. Pregnancy often influences consideration of etiology, treatment, and prognosis. In women of childbearing age with known acquired or genetic neuromuscular disorders, pregnancy should be anticipated and appropriate counseling provided. An interdisciplinary approach with other medical specialties is often necessary.

Peripheral Nervous System Metastases as Complications of Systemic Cancer

Cancer is an important cause of peripheral nervous system (PNS) dysfunction. In addition to toxic effects of chemotherapy and paraneoplastic disorders, one must also consider direct involvement of the PNS by metastatic disease. Neurologic dysfunction in PNS metastatic disease occurs from direct compression or infiltration by cancer. The location of involvement determines the patient’s presentation. Metastatic disease can affect motor neuron, sensory or autonomic ganglia, nerve roots, plexus, cranial and peripheral nerves, and muscle. PNS metastases often cause severe pain. Neurologic deficits are progressive if untreated. Treatment of metastases to the PNS is typically palliative and can include chemotherapy, radiation, surgery and pain management. The response to therapy is variable and may be temporary. Optimizing pain control and maximizing neurologic function and quality of life are important goals of treatment.

On the double: Early immunotherapy speeds recovery of ocular myasthenic weakness: Editorial

No abstract is available for this article. This article is protected by copyright. All rights reserved.

Neuromuscular ultrasound findings in eosinophilic fasciitis: A case series and literature review

Eosinophilic fasciitis (EF) is a rare condition characterized by inflammation, thickening, and sclerosis of the skeletal muscle fascia.1 It can present with a variety of symptoms including induration and peau d’orange changes of the skin, stiffness in the distal limbs, arthralgias, myalgias, and joint contractures. Laboratory abnormalities may include elevated erythrocyte sedimentation rate (ESR), hypergammaglobulinemia, and peripheral eosinophilia.2-4 Electromyography (EMG) is either normal or demonstrates small voluntary motor unit potentials with early recruitment as can be seen in myopathic disorders. The diagnosis of EF typically relies on full thickness incisional biopsy, but interest in the application of imaging modalities including ultrasound (US) and magnetic resonance imaging (MRI) has increased in the past decade. We present three patients in whom imaging assisted in the diagnosis of EF. A systematic review of the literature identified additional cases.

Neuromuscular Disorders in Pregnancy

Abstract Neuromuscular disorders may present and progress differently in women than in men. During pregnancy, medication adjustment, hormonal effects, and other alterations in physiology may influence the manifestation of a variety of neuromuscular disorders. The expression of existing conditions may change; previously asymptomatic conditions may be unmasked, or entirely new conditions may develop. Additionally, neuromuscular disorders and their treatments may have implications for the fetus. Such factors must be carefully considered when counseling and treating pregnant women and those considering pregnancy. This article reviews considerations specific to women and issues surrounding pregnancy in disorders of the neuromuscular junction, focal neuropathies, and acquired and inherited disorders of the nerve and muscle.