Myasthenia gravis (MG) is a rare autoimmune disease in which the body attacks components of the neuromuscular junction (NMJ), causing weakness of voluntary skeletal muscles and fatigue with repetitive movements. MG especially affects the eyes, peripheral extremities, bulbar system, and respiratory system.1

General Prognosis

In general, most individuals with MG who receive the appropriate treatment for their disease subtype live full, relatively normal lives.2,3 Currently, as a consequence of advancements in treatment and management, the overall mortality rate of persons with MG is estimated to be approximately 3% to 4%; before various technological and pharmaceutical developments were made, the mortality rate was as high as 30% to 40%.3,4 

The prognosis often depends on the severity of symptoms, regions of the body affected, MG subtype and subgroup, age at onset, gender, timeliness and type of treatment, frequency of monitoring, and the number of comorbidities.5-8 The symptoms and outcomes of MG differ so much from person to person that it is often referred to as the “snowflake disease.” No 2 snowflakes are alike in structure, just as no 2 cases of MG are alike.1 

Symptom Severity/Body Region Affected 

The most severe outcome of MG is myasthenic crisis, in which the respiratory muscles are affected. The respiratory muscles contract repeatedly during breathing; fatigue and weakness due to MG may severely reduce their ability to contract, so that respiratory failure develops. A patient in severe myasthenic crisis may require immediate support with mechanical ventilation to offload the respiratory muscles and maintain oxygenation.4  

Involvement of the bulbar system causes dysphagia, increasing the risk for aspiration of food or episodes of choking. Dysphagia may provoke a myasthenic crisis due to aspiration pneumonia or diaphragmatic fatigue.9

Subtypes/Subgroups

The subtypes of MG are determined by the type of serum antibodies and presenting manifestations of the disease. MG autoantibodies attack acetylcholine receptors (AChRs), muscle-specific kinase (MuSK), lipoprotein-related protein 4 (LRP-4), and agrin; all of these are components regulating the post-synaptic NMJ. A small proportion of individuals who present clinically with symptoms of MG are antibody-negative.8 Dysfunction of the thymus (evidenced by thymic hyperplasia or thymomas) contributes to the development of the anti-AChR subtype of MG. Immune cells mature and are sensitized to recognize self from non-self in the thymus.10  

The medical literature recognizes 2 forms of MG: ocular and generalized. In approximately 50% of patients, the first noticeable symptoms involve vision. Ocular MG is associated with diplopia, bilateral ptosis, and difficulty focusing, whereas generalized MG causes weakness and fatigue in other regions of the body, including the arms, legs, neck, and muscles involved in breathing and swallowing.11 The risk for mortality is greater with generalized MG, which is associated with the dysfunction of critical musculature, than with purely ocular MG. 

No more than 15% of individuals with ocular MG have only eye muscle weakness at 2 years after symptom onset.1,2,4,11 Typically within the first year, ocular MG progresses to generalized MG,4 although the evidence reported in the scientific literature regarding the probability of progression is conflicting. Some sources state that the conversion of ocular MG to generalized MG occurs within 2 years after onset in 50% to 85% of individuals with ocular MG.7,11 However, a recent study indicated that the risk for the conversion of ocular to generalized MG is low (23.7%), and that immunosuppressive therapy prevents disease progression.12 

Factors associated with a higher risk for conversion from ocular to generalized MG included thymic abnormalities and a positive response to repetitive facial nerve stimulation via electromyography. A positive response, defined as an activity decrease of more than 10% in the nasalis or orbicularis oculi muscles, indicates a diagnosis of ocular MG.12

Age at Disease Onset 

The onset of symptoms of MG is classified as early (before or at age 40) or late (after age 40).7,13 Age younger than 40 years at onset and time to diagnosis of less than 1 year following the appearance of symptoms predict disease remission.6,7,13 In one study, the disease of approximately 38% of individuals with MG went into remission.7 Stabilization or even regression of symptoms at 3 years after disease onset is typical in patients with MG.1,2,4 Approximately 50% of deaths occur during the first 3 years, when the symptoms are most severe.4

Gender

Gender does not influence disease prognosis.6,7,13 

Treatments Influencing Prognosis

Improved intensive care and faster, more accurate diagnostic techniques have affected disease course and outcomes.3 When MG is untreated, the incidence of aspiration, pneumonia, falls, and myasthenic crisis is increased.1,4 Some individuals have refractory MG, which is resistant to available treatments.1

Except in patients with refractory MG, first-line treatment with immunosuppressants has successfully reduced MG-related mortality from 70% in the 1930s to less than 10% currently.5 Patients with refractory MG require intensive disease monitoring and the rapid implementation of treatment within the early phase of their disease, soon after symptom onset.5

According to the literature, 2 treatments influence prognosis—thymectomy and immunosuppressants. In patients with MG and thymic hyperplasia, thymectomy has been found to achieve complete, stable disease remission.1,13 One study noted that thymectomy followed by the administration of high-dose prednisolone increased the likelihood of MG remission.14

References

  1. Myasthenia gravis life expectancy. Myasthenia-Gravis.com. Accessed February 9, 2022.
  2. Myasthenia gravis: treatment & symptoms. Cleveland Clinic. Accessed February 9, 2022.
  3. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44. doi:10.1186/1750-1172-2-44
  4. Jowkar AA. What is the prognosis of myasthenia gravis (MG)? Medscape. Updated August 18, 2018. Accessed February 9, 2022. 
  5. Jeong S, Noh Y, Oh IS, Hong YH, Shin JY. Survival, prognosis, and clinical feature of refractory myasthenia gravis: a 15-year nationwide cohort study. J Korean Med Sci. 2021;36(39). doi:10.3346/jkms.2021.36.e242
  6. Mao ZF, Mo XA, Qin C, Lai YR, Olde Hartman TC. Course and prognosis of myasthenia gravis: a systematic review. Eur J Neurol. 2010;17(7):913-921. doi:10.1111/j.1468-1331.2010.03017.x
  7. Wang L, Zhang Y, He M. Clinical predictors for the prognosis of myasthenia gravis. BMC Neurol. 2017;17. doi:10.1186/s12883-017-0857-7
  8. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023-1036. doi:10.1016/S1474-4422(15)00145-3
  9. Cohen MS, Younger D. Aspects of the natural history of myasthenia gravis: crisis and death. Ann N Y Acad Sci. 1981;377:670-677. doi:10.1111/j.1749-6632.1981.tb33765.x
  10. Cavalcante P, Le Panse R, Berrih-Aknin S, et al. The thymus in myasthenia gravis: site of “innate autoimmunity”?  Muscle Nerve. 2011;44(4):467-484. doi:10.1002/mus.22103
  11. Ocular myasthenia gravis. Brigham and Women’s Hospital. Accessed February 9, 2022.
  12. Witthayaweerasak J, Rattanalert N, Aui-aree N. Prognostic factors for conversion to generalization in ocular myasthenia gravis. Medicine. 2021;100(19):e25899. doi:10.1097/MD.0000000000025899
  13. Yang J, Liu C, Li T, Li C. Prognosis of thymectomy in myasthenia gravis patients with thymus hyperplasia. Int J Neurosci. 2017;127(9):785-789. doi:10.1080/00207454.2016.1257993
  14. Wakata N, Iguchi H, Sugimoto H, Nomoto N, Kurihara T. Relapse of ocular symptoms after remission of myasthenia gravis–a comparison of relapsed and complete remission cases. Clin Neurol Neurosurg. 2003;105(2):75-77. doi:10.1016/s0303-8467(02)00104-x

Reviewed by Harshi Dhingra, MD, on 2/10/2022.

READ MORE ON