Myasthenia gravis classification
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2], Keanu Ngo[3]
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Overview
Myasthenia gravis (MG) is not defined by a single list of subtypes but is classified along several complementary axes that are applied together: clinical distribution (ocular vs generalized), severity by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, autoantibody status (AChR, MuSK, LRP4, or seronegative), age at onset (juvenile, early-, late-, and very-late-onset), and the presence of a thymoma. These axes carry prognostic and therapeutic implications and are used in combination to define the clinically actionable subgroup. The genetically determined congenital myasthenic syndromes are antibody-negative disorders of the neuromuscular junction and are distinct from autoimmune MG.
Classification
Clinical Distribution (Ocular vs Generalized)
- Ocular MG is confined to the extraocular muscles (ptosis, diplopia) for an extended period.[1]
- Generalized MG involves bulbar, facial, axial, respiratory, and/or limb muscles. Most patients present with ocular symptoms; approximately 50–80% generalize, usually within 2 years, after which conversion becomes unlikely.[2]
MGFA Clinical Classification (Severity)
The MGFA Clinical Classification replaced the older Osserman system and grades maximal severity and distribution:[3][4]
- Class I: Ocular weakness only; all other muscle strength normal.
- Class II: Mild generalized weakness (IIa limb/axial-predominant; IIb bulbar/respiratory-predominant).
- Class III: Moderate generalized weakness (IIIa/IIIb as above).
- Class IV: Severe generalized weakness (IVa/IVb as above).
- Class V: Intubation, with or without mechanical ventilation (routine postoperative use excluded); a feeding tube without intubation is classified as IVb.
The MGFA class is subjective and non-linear and, per the MGFA Task Force, should not be used to measure treatment response. The MGFA Post-Intervention Status (e.g., complete stable remission, pharmacologic remission, minimal manifestations) together with a quantitative scale such as the Quantitative Myasthenia Gravis (QMG) score is used for that purpose.[5]
Serologic (Antibody) Subgroups
- AChR antibody-positive: ~80–85% of generalized and ~50% of ocular MG; antibodies are predominantly complement-activating IgG1/IgG3.[1][6]
- MuSK antibody-positive: ~5–8% of MG; predominantly non-complement-activating IgG4; prominent facial, bulbar, and respiratory involvement, frequent crises, and poor response to acetylcholinesterase inhibitors.[7][8]
- LRP4 antibody-positive: ~1–5% of MG and a highly variable proportion (~1–54%) of double-seronegative patients depending on geography and assay; predominantly IgG1; may co-occur with AChR or MuSK antibodies and in healthy individuals.[1][9]
- Seronegative: No AChR or MuSK antibodies on standard radioimmunoassay (~10–15%). Live or fixed cell-based assays detect clustered-AChR or MuSK antibodies in roughly one-third of these patients (in one large cohort, 19.5% clustered AChR and 8.5% MuSK).[10][11]
Age at Onset (AChR-MG)
- Juvenile-onset: ≤18 years.[1]
- Early-onset (EOMG): <50 years; female predominance, thymic follicular hyperplasia, higher AChR titers.[12][13]
- Late-onset (LOMG): ≥50 years; male predominance, thymic atrophy, frequent striational antibodies (titin, ryanodine receptor).[14][13]
- Very-late-onset (VLOMG): ≥65 years; increasingly common, high AChR positivity, low frequency of thymic abnormalities.[15]
The 50-year cutoff is conventional but not universal (thresholds of 40–65 years have been used).[14][12]
Thymoma-Associated MG (TAMG)
A distinct paraneoplastic subgroup considered separately from the age-defined groups. Thymoma occurs in ~10–15% of MG patients; TAMG is nearly always AChR antibody-positive (99–100%), presents around age 50–55 with no clear sex predilection, is usually generalized, and carries a higher risk of myasthenic crisis.[16][13]
Distinction From Congenital Myasthenic Syndromes
- Congenital myasthenic syndromes (CMS) are inherited (Mendelian) defects in neuromuscular-junction genes (presynaptic, synaptic, or postsynaptic), are antibody-negative, and are not a subtype of autoimmune MG (see Myasthenia gravis differential diagnosis).[17]
- Transient neonatal MG is autoimmune, caused by passive transplacental transfer of maternal antibodies; it occurs in ~10–20% of infants of mothers with MG and resolves over weeks to ~3 months (see Myasthenia gravis natural history, complications, and prognosis).[18]
References
- ↑ 1.0 1.1 1.2 1.3 Punga AR, Maddison P, Heckmann JM, Guptill JT, Evoli A (February 2022). "Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders". Lancet Neurol. 21 (2): 176–188. doi:10.1016/S1474-4422(21)00297-0.
- ↑ Pesa J, Choudhry Z, de Courcy J, et al. (April 2025). "Factors associated with increased severity of generalized myasthenia gravis among patients in the United States and Europe". Sci Rep. 15. doi:10.1038/s41598-025-96401-z.
- ↑ Mendoza M, Tran C, Bril V, Katzberg HD, Barnett C (September 2020). "Patient-Acceptable Symptom States in Myasthenia Gravis". Neurology. 95 (12): e1617–e1628. doi:10.1212/WNL.0000000000010574.
- ↑ Baruca M, Leonardis L, Podnar S, et al. (December 2016). "Single fiber EMG as a prognostic tool in myasthenia gravis". Muscle Nerve. 54 (6): 1034–1040. doi:10.1002/mus.25174.
- ↑ Sanders DB, Raja SM, Guptill JT, et al. (February 2021). "The Duke myasthenia gravis clinic registry: I. Description and demographics". Muscle Nerve. 63 (2): 209–216. doi:10.1002/mus.27120.
- ↑ El-Wahsh S, Ramanathan S, Reddel S (August 2025). "Clinical utility of autoantibodies in the diagnosis and management of myasthenia gravis". J Neuroimmunol. 405: 578633. doi:10.1016/j.jneuroim.2025.578633.
- ↑ Morren J, Li Y (September 2018). "Myasthenia gravis with muscle-specific tyrosine kinase antibodies: A narrative review". Muscle Nerve. 58 (3): 344–358. doi:10.1002/mus.26107.
- ↑ Iorio R (February 2024). "Myasthenia gravis: the changing treatment landscape in the era of molecular therapies". Nat Rev Neurol. 20 (2): 84–98. doi:10.1038/s41582-023-00916-w.
- ↑ Preßler H, Stascheit F, Aigner A, et al. (August 2026). "Phenotype, Severity, and Therapy of Patients With LRP4 Antibody-Associated Myasthenia Gravis in the German Myasthenia Gravis Registry". Neurology. doi:10.1212/WNL.0000000000214163.
- ↑ Damato V, Spagni G, Monte G, et al. (September 2022). "Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis". J Neurol Neurosurg Psychiatry. 93 (9): 995–1000. doi:10.1136/jnnp-2022-329284. PMID 35835469 Check
|pmid=value (help). - ↑ Kaminski HJ, Sikorski P, Coronel SI, Kusner LL (June 2024). "Myasthenia gravis: the future is here". J Clin Invest. 134 (12). doi:10.1172/JCI179742.
- ↑ 12.0 12.1 Cortés-Vicente E, Álvarez-Velasco R, Segovia S, et al. (March 2020). "Clinical and therapeutic features of myasthenia gravis in adults based on age at onset". Neurology. 94 (11): e1171–e1180. doi:10.1212/WNL.0000000000008903.
- ↑ 13.0 13.1 13.2 Meriggioli MN, Sanders DB (May 2009). "Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity". Lancet Neurol. 8 (5): 475–490. doi:10.1016/S1474-4422(09)70063-8.
- ↑ 14.0 14.1 Latini E, Guida M, Cepele A, Maestri Tassoni M (September 2026). "Late-onset myasthenia gravis: an increasingly frequent clinical entity with distinctive challenges". Muscle Nerve. 74 (3). doi:10.1002/mus.28456.
- ↑ Liampas I, Demiri S, Malataras G, et al. (July 2026). "Very late-onset myasthenia gravis: a systematic review and meta-analysis of sex distribution, thymic pathology and autoantibodies". J Neurol. 273. doi:10.1007/s00415-026-13711-y.
- ↑ Claytor B, Delasos L, Raymond DP, et al. (October 2026). "Myasthenia gravis and thymoma". Muscle Nerve. 74 (4). doi:10.1002/mus.28502.
- ↑ Vrinten C, van der Zwaag AM, Weinreich SS, Scholten RJ, Verschuuren JJ (December 2014). "Ephedrine for myasthenia gravis, neonatal myasthenia and the congenital myasthenic syndromes". Cochrane Database Syst Rev (12): CD010028. doi:10.1002/14651858.CD010028.pub2.
- ↑ Punga AR, Maddison P, Heckmann JM, Guptill JT, Evoli A (February 2022). "Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders". Lancet Neurol. 21 (2): 176–188. doi:10.1016/S1474-4422(21)00297-0.