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Myasthenia Gravis

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MG Types

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies attach to acetylcholine receptors (AChRs) or functionally similar structures in the post-synaptic membrane at the neuromuscular junction (NMJ). The result is impairment of neuromuscular transmission and skeletal muscular weakness, which is the main symptom of MG.The disease is either generalized or localized and is characterized by muscle weakness and fatigue.1,2 The overall prevalence is 150 to 250 per million people, and the annual incidence is 8 to 10 cases per million person-years.3

Clinical Classification 

The clinical classification of the Myasthenia Gravis Foundation of America separates MG into 5 principal categories on the basis of the clinical characteristics and severity of the disease. Each class varies in prognosis or therapeutic response.4,5 

  • Class I: Any ocular muscle weakness, possible ptosis, no evidence of muscle weakness elsewhere
  • Class II: Mild weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
    • Class IIa: Predominantly affecting limb or axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
    • Class IIb: Predominantly bulbar and/or respiratory muscles; may also have lesser or equal involvement of limb or axial muscles, or both
  • Class III: Moderate weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
    • Class IIIa: Predominantly affecting limb or axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
    • Class IIIb: Predominantly affecting bulbar and/or respiratory muscles; may also have lesser or equal involvement of limb or axial muscles, or both
  • Class IV: Severe weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
    • Class IVa: Predominantly affecting limb or axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
    • Class IVb: Predominantly affecting bulbar and/or respiratory muscles; may also have lesser or equal involvement of limb, axial muscles, or both (can also include feeding tube without intubation)
  • Class V: Intubation needed to maintain airway, with or without mechanical ventilation

Another classification system, based on clinical features and antibodies type, divides MG into many groups. Each group has a varied response to treatment and therefore a prognostic value4,6:

  • Early-onset MG: Age at onset of less than 50 years with thymic hyperplasia
  • Late-onset MG: Age at onset of more than 50 years with thymic atrophy
  • Thymoma-associated MG
  • MG with anti-muscle-specific kinase (anti-MuSK) antibodies
  • Ocular MG: Symptoms arising solely from periocular muscles
  • MG with nondetectable AChR and MuSK antibodies

Ocular Myasthenia Gravis

Ocular myasthenia gravis (OMG) is a form of MG in which weakness is limited clinically to the extraocular muscles, the levator palpebrae superioris, and the orbicularis oculi. In more than half of patients with MG, ptosis and diplopia are the first manifestations of the disease. In 50% to 80% of these cases, generalized illness develops later. Most cases (90%) of OMG progress to the generalized form within the first 2 years after the onset of ocular symptoms.7

Only 20% of cases of MG remain purely ocular and never progress to the generalized form, and only 50% of people with this form of MG have detectable AChR antibodies, which makes the diagnosis difficult. In individuals without detectable antibodies, the results of single-fiber electromyography (EMG) can detect failure of neuromuscular transmission, including OMG. Differential diagnoses include ocular manifestations of thyroid disease and progressive external ophthalmoplegia associated with mitochondrial disease. When OMG is diagnosed, the first course of treatment should be pyridostigmine to control symptoms and assess reversibility. If the patient remains symptomatic despite receiving maximum doses of pyridostigmine, corticosteroids should be administered as soon as possible.8 

Generalized Myasthenia Gravis

In generalized MG, the bulbar, limb, and respiratory muscles are involved.7 Generalized weakness develops in approximately 75% of affected individuals, usually in the first 2 to 3 years after the onset of symptoms. Generalization occurs sooner in patients with anti-MuSK MG. Bulbar dysfunction occurs in 10% to 15% of cases. Patients experience difficulty chewing as a result of jaw fatigue that develops as they eat. Additionally, weakening of the pharyngeal or tongue muscles can impede swallowing; liquid dysphagia is more common than solid dysphagia. Some patients report nasal regurgitation of fluid or fits of coughing after eating or drinking; the coughing is due to aspiration caused by a predisposition to involvement of the soft palate.9 

A lack of facial expression, difficulty smiling and whistling, and failure to close the eyelids adequately are due to bilateral facial weakness. Patients may experience social discomfort as a result of their lack of facial expression. Weakness of neck flexion is a major symptom. Patients with anti-MuSK MG tend to present with head drop as a result of neck extensor weakness. When limb weakness arises, the proximal muscles are more likely to be involved, so that the ability to raise the arms, climb stairs, or rise from a low chair is limited.9

Weakness of the respiratory muscles may affect up to 40% of patients with MG, resulting in exertional dyspnea or orthopnea. Myasthenic crisis is characterized by respiratory failure requiring noninvasive positive pressure ventilation or mechanical ventilation until clinical recovery. Myasthenic crisis affects about 15% to 20% of patients with MG and is more prevalent in those with anti-MuSK MG.9

Pyridostigmine is the medication most frequently prescribed for symptoms. Neostigmine is an acetylcholinesterase inhibitor that can also be used for treatment. The principal immunomodulatory medication in the long-term care of patients with MG is prednisolone or prednisone.8 

References

  1. Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375(26):2570-2581. doi:10.1056/NEJMra1602678
  2. Thanvi BR, Lo TC. Update on myasthenia gravis. Postgrad Med J. 2004;80(950):690-700. doi:10.1136/pgmj.2004.018903
  3. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primers. 2019;5(1):30. doi:10.1038/s41572-019-0079-y
  4. Gilhus NE, Owe JF, Hoff JM, Romi F, Skeie GO, Aarli JA. Myasthenia gravis: a review of available treatment approaches. Autoimmune Dis. 2011;2011:847393. doi:10.4061/2011/847393
  5. Jaretzki A 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000;55(1):16-23. doi:10.1212/wnl.55.1.16
  6. Beloor Suresh A, Asuncion RMD. Myasthenia gravis. In: StatPearls [Internet]. Updated August 11, 2021. Accessed February 4, 2022. 
  7. Nair AG, Patil-Chhablani P, Venkatramani DV, Gandhi RA. Ocular myasthenia gravis: a review. Indian J Ophthalmol. 2014;62(10):985-991. doi:10.4103/0301-4738.145987
  8. Farrugia ME, Goodfellow JA. A practical approach to managing patients with myasthenia gravis-opinions and a review of the literature. Front Neurol. 2020;11:604. doi:10.3389/fneur.2020.00604
  9. Hehir MK, Silvestri NJ. Generalized myasthenia gravis: classification, clinical presentation, natural history, and epidemiology. Neurol Clin. 2018;36(2):253-260. doi:10.1016/j.ncl.2018.01.002

Reviewed by Kyle Habet, MD, on 2/14/2022.

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