Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 24-34: Disorders of Neuromuscular Transmission + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Fluctuating weakness of voluntary muscles, producing symptoms such as Diplopia Ptosis Difficulty in swallowing Activity increases weakness of affected muscles Short-acting anticholinesterases transiently improve the weakness +++ General Considerations ++ Occurs at all ages, sometimes in association with Thymic tumor Thyrotoxicosis Rheumatoid arthritis Lupus erythematosus Onset is usually insidious, but the disorder is sometimes unmasked by a coincidental infection Exacerbations may occur before the menstrual period and during or shortly after pregnancy Symptoms are due to blocks of neuromuscular transmission caused by autoantibodies binding to acetylcholine receptors The external ocular muscles and certain other cranial muscles, including the masticatory, facial, and pharyngeal muscles, are especially likely to be affected The respiratory and limb muscles may also be involved +++ Demographics ++ Most common in young women with HLA-DR3 If thymoma is associated, older men are more commonly affected + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Initial symptoms Ptosis Diplopia Difficulty in chewing or swallowing Respiratory difficulties Limb weakness Some combination of these problems Weakness May remain localized to a few muscle groups, especially the ocular muscles May become generalized Symptoms often fluctuate in intensity during the day This diurnal variation is superimposed on a tendency to longer-term spontaneous relapses and remissions that may last for weeks Clinical examination confirms the weakness and fatigability of affected muscles Extraocular palsies and ptosis, often asymmetric, are common Pupillary responses are normal The bulbar and limb muscles are often weak, but the pattern of involvement is variable Sustained activity of affected muscles increases the weakness, which improves after a brief rest Sensation is normal Usually no reflex changes +++ Differential Diagnosis ++ Lambert-Eaton myasthenic syndrome (usually paraneoplastic) Botulism Aminoglycoside-induced neuromuscular weakness + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Elevated level of serum acetylcholine receptor antibodies has a sensitivity of 80–90% Certain patients have serum antibodies to muscle-specific tyrosine kinase (MuSK), which should be determined These patients are more likely to have facial, respiratory and proximal muscle weakness than those with antibodies to acetylcholine receptors Other associated antibodies Low-density lipoprotein receptor-related protein 4 (LRP4) Agrin Tests for these antibodies are not widely commercially available +++ Imaging Studies ++ CT scan of the chest with and without contrast Should be obtained to demonstrate a coexisting thymoma However, normal studies do not exclude this possibility +++ Diagnostic Procedures ++ Electrophysiology Demonstration of a decrementing muscle response to repetitive 2- or 3-Hz stimulation of motor nerves indicates a disturbance of neuromuscular transmission Such an abnormality may even be detected in clinically strong muscles with certain provocative procedures Needle electromyography Shows a marked variation in configuration and size of individual motor unit potentials in affected muscles Single-fiber electromyography reveals an increased jitter, or variability, in the time interval between two muscle fiber action potentials from the same motor unit + Treatment Download Section PDF Listen +++ +++ Medications ++ Drugs, such as aminoglycosides, that may exacerbate myasthenia gravis should be avoided Anticholinesterase drugs provide symptomatic benefit without influencing the course of the disease Neostigmine, pyridostigmine, or both can be used Dose is determined on an individual basis Usual dose of neostigmine, 7.5–30 mg four times daily orally (average, 15 mg) Usual dose of pyridostigmine, 30–180 mg four times daily orally (average, 60 mg) Overmedication may temporarily increase weakness Corticosteroids Indicated if there has been a poor response to anticholinesterase drugs Start while the patient is in the hospital, since weakness may initially be aggravated Prednisone can be started at 20 mg orally daily and increased by 10 mg increments weekly to a target of 1 mg/kg/day (maximum daily dose 100 mg) For patients who are hospitalized with severe myasthenia and are receiving intravenous immunoglobulin or plasmapheresis, 1 mg/kg/day (maximum daily dose 100 mg) of prednisone can be given initially because the more rapid onset of action of immunoglobulin or plasmapheresis mitigates the initial dip in strength due to corticosteroids Once patient is stabilized at the initial high dose, corticosteroids can gradually be tapered to a relatively low maintenance level (eg, 10 mg prednisone orally daily) as improvement occurs; total withdrawal is difficult, however Can be prescribed as alternate-day or daily treatment, with alternate-day therapy potentially mitigating side effects Azathioprine May be effective in allowing a lower dose of corticosteroids Usual dose, 2–3 mg/kg/day orally after a lower initial dose Other immunosuppressive agents that are used to reduce the corticosteroid dose include Mycophenolate mofetil Rituximab Cyclosporine Methotrexate Tacrolimus Plasmapheresis or intravenous immunoglobulin therapy May be helpful in patients with major disability May also be useful for stabilizing patients before thymectomy and for managing acute crisis Have similar efficacy Eculizumab, a complement inhibitor Approved by the FDA for disease refractory to at least two alternate immunosuppressive therapies Dosage: 900 mg intravenously weekly for 4 doses, followed by 1200 mg at week 5, then 1200 mg every 2 weeks Vaccination against meningococcus is required prior to receiving eculizumab +++ Surgery ++ Thymectomy Usually leads to symptomatic benefit or remission Should be considered in all patients younger than age 65, unless weakness is restricted to the extraocular muscles If the disease is of recent onset and only slowly progressive, operation is sometimes delayed for a year or so, in the hope that spontaneous remission will occur + Outcome Download Section PDF Listen +++ +++ Complications ++ Aspiration pneumonia Life-threatening exacerbations of myasthenia (so-called myasthenic crisis) may lead to respiratory weakness requiring immediate admission to the intensive care unit +++ Prognosis ++ The disorder follows a slowly progressive course and may have a fatal outcome owing to respiratory complications such as aspiration pneumonia +++ When to Refer ++ All patients +++ When to Admit ++ Patients with acute exacerbation or respiratory involvement Patients requiring plasmapheresis For thymectomy + References Download Section PDF Listen +++ + +Farmakidis C et al. Treatment of myasthenia gravis. Neurol Clin. 2018 May;36(2):311–37. [PubMed: 29655452] + +Muppidi S et al; Regain Study Group. Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve. 2019 Jul;60(1):14–24. [PubMed: 30767274]