Phys · neurological
Myasthenia Gravis
Also known as myasthenia gravis · MG · fatigable weakness · acetylcholine receptor antibody myasthenia · AChR-MG · MuSK antibody myasthenia · MuSK-MG · seronegative myasthenia · ocular myasthenia · myasthenic crisis · cholinergic crisis · penicillamine-induced myasthenia · immune checkpoint inhibitor myasthenia
Consultant-physician-depth guide to myasthenia gravis: autoimmune neuromuscular junction pathology (anti-AChR, anti-MuSK), fatigable weakness across ocular, bulbar, limb and respiratory muscles, bedside and serological diagnosis, pyridostigmine and immunosuppression, thymectomy (MGTX), and myasthenic crisis management for FRACP DWE and DCE preparation.
On this page
Study tools
Your progress
Saved on this device.
Practise this topic
Target exams
Red flags
- Myasthenic crisis — respiratory or bulbar failure from MG weakness — is a neurological emergency; assess FVC and negative inspiratory force early and escalate to HDU/ICU before the patient decompensates
- A deteriorating MG patient who is increasingly breathless, has a weak bovine cough, or cannot count to 20 on one breath is heading toward intubation; do not assume it is anxiety
- New-onset or rapidly worsening MG after an immune checkpoint inhibitor (pembrolizumab, nivolumab) can be severe and may coexist with myocarditis — assess troponin and admit for urgent immunotherapy
- Thymoma is present in 10 to 15 per cent of MG patients and is occasionally malignant — CT thorax is mandatory at diagnosis; a mediastinal mass in an MG patient is a thymoma until proven otherwise
- Giving intravenous magnesium to an MG patient for an arrhythmia or pre-eclampsia can precipitate catastrophic respiratory failure — magnesium inhibits ACh release and is relatively contraindicated
Myasthenia Gravis
The answer first
Myasthenia gravis (MG) is an autoimmune disorder of the postsynaptic neuromuscular junction in which pathogenic antibodies reduce the number or function of acetylcholine receptors (AChRs), producing fatigable weakness — weakness that worsens with sustained activity and improves with rest. It is the commonest disorder of neuromuscular transmission. The two questions that drive every clinical decision in MG are: is this truly fatigable weakness (and not a fixed myopathy, a cranial nerve palsy, or Lambert-Eaton)? and which antibody subtype is it (AChR, MuSK, or seronegative)? — because the antibody determines the phenotype, the response to treatment, and the role of thymectomy. [1]
The clinical decision rules a registrar must own at viva: [1]
- Fatigability is the diagnosis. A single normal examination does not exclude MG — a patient with variable ptosis or diplopia must be tested under fatiguing conditions: sustained upgaze for one minute, repeated eye opening, or the ice pack test. The signature is variability with use.
- Antibody subtype changes management. Anti-AChR antibodies are present in about 85 per cent of generalized MG; anti-MuSK in about 5 to 8 per cent; the remainder are seronegative. MuSK-MG is a different disease — prominent bulbar and respiratory weakness, female predominance, poor response to pyridostigmine (which can worsen it), and no benefit from thymectomy [9]. Rituximab is particularly effective in MuSK-MG [10].
- Pyridostigmine is symptomatic, not disease-modifying. It improves most AChR-MG but does not alter the immune attack. Generalized MG needs immunosuppression (prednisolone plus a steroid-sparing agent) to achieve and maintain remission [2].
- Myasthenic crisis is a respiratory emergency. Assess vital capacity and negative inspiratory force early. A worsening patient needs IVIG or plasma exchange for rapid immunotherapy and ventilatory support — not more pyridostigmine, unless there are clear cholinergic signs (sweating, salivation, miosis, fasciculations) suggesting cholinergic crisis.
The organising principle is antibody-stratified, escalation-based management: confirm fatigability, identify the antibody, start symptomatic and immunosuppressive therapy, screen for thymoma, and reserve biological therapy (rituximab, eculizumab, FcRn inhibitors) for refractory disease. [1]
References10ShowHide
- [1]Jaretzki A III, 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.PMID 10891897
- [2]Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: Executive summary Neurology, 2016.PMID 27358333
- [3]Narayanaswami P, Sanders DB, Wolfe G, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update Neurology, 2021.PMID 33144515
- [4]Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized Trial of Thymectomy in Myasthenia Gravis N Engl J Med, 2016.PMID 27509100
- [5]Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis Nat Rev Dis Primers, 2019.PMID 31048702
- [6]Howard JF Jr, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study Lancet Neurol, 2017.PMID 29066163
- [7]Mantegazza R, Wolfe GI, Muppidi S, et al. Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension Neurology, 2021.PMID 33229455
- [8]Pasnoor M, Wolfe GI, Nations S, et al. Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience Muscle Nerve, 2010.PMID 19882635
- [9]Clifford KM, Hobson-Webb LD, Benatar M, et al. Thymectomy may not be associated with clinical improvement in MuSK myasthenia gravis Muscle Nerve, 2019.PMID 30575980
- [10]Litchman T, Roy B, Kumar A, et al. Differential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study J Neurol Sci, 2020.PMID 32028072