June is myasthenia gravis (MG) awareness month. MG is a disorder of the neuromuscular junction leading to clinical manifestations that include muscular weakness and fatigability. MG has a prevalence of 200 in 100,000 individuals, most commonly affecting women at a ratio of 3:2. The peak age of onset for women occurs between the ages of 20-30 and between the ages of 50-60 for men.  While prognosis has improved greatly with advancing treatments, there continues to be a wide variability in prognosis and progression of disease, with a cure yet to be identified.

The primary defect in MG is that patients have a decreased amount of acetylcholine receptors (AChRs) at the neuromuscular junction because of an antibody-mediated autoimmune attack. Patients with MG also have defective post-synaptic folds. These changes do not allow for proper uptake of acetylcholine (ACh), thus inhibit proper neuromuscular transmission. This is further complicated by the normal physiologic process of muscles releasing less ACh during continued exercise, causing patients with MG to have increasing fatigue with continued exertion.

Patients with MG experience weakness with progressive fatigability.  Due to mechanisms described above, weakness may improve with rest.  The cranial muscles are often the first involved, with patients demonstrating weakness of the eyelids, extraocular movements, difficulty with facial expressions, chewing, swallowing, and tongue weakness. Patients may also exhibit speech difficulties due to tongue weakness. This oropharyngeal weakness may lead to severe complications, such as aspiration pneumonia. If weakness is restricted to the extraocular muscles for 3 years, the patient is not likely to develop more generalized symptoms, and is diagnosed with ocular MG.  However, about 85% of patients do develop more generalized symptoms, including limb weakness.  Associated limb weakness may be asymmetric, and is often proximal.  Deep tendon reflexes are preserved. Patients with MG may experience unrelated infections or illnesses that precipitate a myasthenic crisis, which causes acute worsening of their symptoms.  A myasthenic crisis is defined as an exacerbation exhibiting muscular weakness sufficient to endanger the patient’s life. If patients require mechanical ventilation they are considered in crisis.

The diagnosis of MG should be confirmed before initiation of treatment. The history and physical exam is an invaluable part of diagnosis. Autoantibodies can be detected in about 85% of all patients with MG, but only in about 50% of patients with ocular MG. A positive antibody test confirms MG, but a negative test does not exclude it. Other tests that will not be covered in depth in this post include electrodiagnostic testing, ice pack testing, and anticholinesterase test.

Advances in treatment have resulted in dramatic improvements in outcomes of patients with MG.  Treatments include anticholinesterase inhibitors, immunosuppressants, thymectomy, intravenous immunoglobulin (IVIg), and in select groups, plasmapheresis.  Pyridostigmine is the most commonly utilized anticholinergic medication used to treat MG. Individual responses vary, but positive effects typically last 3-4 hours. Anticholinergic medications very in effectiveness, but produce partial improvement in most patients, with some patients experiencing complete, albeit temporary, improvement in symptoms. Examples of immunotherapy drugs that may be used include glucocorticoids, azathioprine, cyclosporine, mycophenolate mofetil, rituximab, tacrolimus, and cyclophosphamide.  Recent literature supports thymectomy as a treatment for MG, demonstrating that patients have improved strength and overall function.  They also demonstrate a decreased need for steroid treatment, second-line treatment agents, and have fewer exacerbations. 

Mortality has declined dramatically with recent advances in treatment.  About 80% of patients require long-term immunosuppressive therapies.  The remaining 20% of patients can be tapered off therapy and achieve remission.  Thymectomy is being explored as an option to achieve higher rates of remission, but additional data is needed to determine how this procedure will impact remission rates.

Read more here:

Harrison's Principles of Internal Medicine, 20e: Chapter 440: Myasthenia Gravis and Other Diseases of the Neuromuscular Junction

Principles of Rehabilitation Medicine: Chapter 74: Disorders of the Neuromuscular Junction: Myasthenia Gravis