Autoimmune Neuromuscular Diseases

I am thrilled to share these comprehensive, clinically focused reviews on topics describing neuromuscular mechanisms as targets of the immune system. The immune system may affect different areas of the peripheral nervous system, including nerve, neuromuscular junction, and muscle with varying presentations and some overlap of symptoms. Accurate recognition of the neuromuscular disease directs appropriate testing strategies to promptly initiate treatment. Isolated weakness may be a feature of any of these diseases, but in combination with bulbar or sensory symptoms points to a more specific diagnosis. Furthermore, recognition of these unique diseases directs effective approaches to alleviate symptoms or to treat the underlying immune pathology. For instance, certain diseases respond to immune modulating or immune suppressant agents, but others may be more refractory.

Drs. Witt, Kodal, and Dysgaard share a fantastic review on the nuances of vasculitic neuropathy types, resulting particularly from small and medium size vessel vasculitides, in association with connective tissue disorders or isolated to the peripheral nervous system (non-systemic vasculitic neuropathy). Vasculitic neuropathy typically presents as a subacute, painful involvement of 2 or more nerves, a mononeuritis multiplex pattern. Supportive investigations for this disorder involve laboratory, electrodiagnostic, and pathological evaluation. Immune suppressant treatment regimens are listed, and the authors highlight the need for more studies on the natural history and pathologic mechanisms of these disorders as well as the need for randomized treatment trials.

Next, Drs. Dansereau and Wang neatly organize the effects of sarcoidosis on the peripheral nervous system into large and small fiber neuropathies and myopathy, emphasizing the important aspects of varying presentations, including multiple classic pathologic images. Only rare series are available to guide treatment decisions. Quantifying and treating small fiber variants is complicated, but new treatment approaches are being evaluated. They discuss the presence of sarcoid granulomas without clear clinical implication and the presence of some interrelationship with inclusion body myositis.

The heterogeneous presentation of chronic inflammatory demyelinating polyneuropathy (CIDP) and its related disorders are comprehensively presented by Drs. Gonzalez Candito and Habib, including the most up to date categorization as well as multiple differential diagnoses of this complex topic. Electrodiagnostic evaluation is described as an important diagnostic tool to assess the degree of demyelination. First-line treatments include intravenous immune globulin (IVIG) and corticosteroids, but multiple other potential therapies and current clinical trials also are considered.

Lambert-Eaton myasthenic syndrome (LEMS) is a disease that involves impaired neuromuscular transmission from antibodies against the voltage-gated calcium channel. Drs. Varon and Dimachkie skillfully point out the importance of recognizing the myriad features of LEMS, including the clinical and electrodiagnostic triads. The identification of the presenting features and the potential association with small cell lung cancer leads to critical management decisions of this rare disorder to appropriately direct patient care for cancer screening, symptomatic relief, or therapies targeting the immune system.

Finally, Dr. Silvestri offers details on the clinical presentation and evaluation of myasthenia gravis (MG), including facets of laboratory and electrodiagnostic testing. He provides an instructive table documenting the burgeoning field of new therapeutic agents, noting the different mechanisms of action. He emphasizes the need for an individualized treatment approach for patients with MG, including the rapid response that is necessary in myasthenic crisis. Clinical trials of numerous innovative treatments for this disease are underway or will begin soon.

In the age of immune-mediated therapeutics, the near future heralds the development of multiple different treatment options. These reviews underscore the need for vigilance in identifying the set of multiple seemingly disparate symptoms to accurately diagnose and treat these diverse neuromuscular diseases. Future directions include additional data population studies, streamlined evaluation and treatment of diseases, and optimized treatment trials with a focus on minimizing adverse risks to individuals and reducing treatment costs.

Thank you to the authors for their contributions.