Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.
A patient with myasthenia gravis can look entirely normal during a brief examination because the weakness fluctuates and recovers with rest. Diagnosis therefore means provoking the weakness first, then proving it sits at the neuromuscular junction rather than in muscle, nerve, or brain.
Provoking weakness at the bedside
Fatiguing manoeuvres outlast the patient’s reserve and expose what rest conceals:
- Sustained upgaze for about 30 seconds — watch for emerging or worsening ptosis and diplopia.
- Sustained lateral gaze for about 30 seconds — produces or worsens diplopia from extraocular fatigue.
- Arm abduction against gravity — watch for progressive drooping of the held limbs.
- Counting aloud on one breath — the voice fades, turns soft and indistinct, then recovers after rest, testing bulbar and respiratory reserve.
- Repetitive movements such as clapping or sit-to-stand — count how many repetitions precede visible weakening.
The time of examination matters. A morning visit may miss disease that an evening visit reveals, and spontaneously resolving ptosis does not mean the disease has gone.
Bedside pharmacological clues
The ice pack test is the most useful bedside confirmatory manoeuvre for ptosis: cooling the drooping eyelid for about 2 minutes produces transient improvement. Cold inhibits acetylcholinesterase at the junction, so acetylcholine lingers longer and stimulates the remaining receptors. The improvement fades soon after the ice is removed, and the test is non-invasive and safe.
Edrophonium, a short-acting acetylcholinesterase inhibitor given intravenously, briefly but dramatically restores strength; because of cardiac risks it is used only with monitoring and has largely receded from routine practice. An oral pyridostigmine trial over days, typically starting from 60 mg doses, can support the diagnosis when symptoms improve with regular dosing, doubling as initial therapy rather than a rapid test.
Electrodiagnosis
Repetitive nerve stimulation is the standard electrical test. A motor nerve is stimulated at low frequency, usually 2–3 Hz, and the muscle response amplitude is recorded across successive stimuli. In myasthenia gravis the amplitude decrements, typically by more than 10% between the first and fourth or fifth response, because each impulse finds fewer functional receptors. The mirror image, an incremental response to rapid stimulation or after brief exercise, points to Lambert-Eaton myasthenic syndrome instead, as detailed in MG versus LEMS.
Single-fibre electromyography is the most sensitive test of junction transmission. A fine electrode records two fibres of one motor unit: the interval between their activations (jitter) widens, and some impulses fail entirely (blocking). Sensitivity comes at the cost of specificity, since any transmission defect can disturb the recording, so the result is read together with the clinical picture.
Antibodies
Antibody testing confirms the disease and predicts its behaviour. Anti-acetylcholine-receptor antibodies are tested first: highly specific at about 99.8%, positive in roughly 85% of generalised and half of ocular cases (Gilhus et al., 2019). A positive result in the right clinical context confirms the diagnosis without further workup.
When receptor antibodies are negative, anti-MuSK testing follows. MuSK-positive disease is predominantly bulbar with minimal ocular signs, responds poorly to pyridostigmine and thymectomy, and responds well to rituximab, so the result changes management. Anti-LRP4 antibodies explain a fraction of double-negative cases and usually behave mildly. The remaining 5–10% are seronegative for all three and are diagnosed clinically with electrodiagnostic support; research antibodies against agrin, cortactin, and related junction proteins may eventually explain some of these cases. Results take days to weeks, so bedside manoeuvres guide immediate decisions while the results are pending.
Imaging
Chest computed tomography is mandatory in every newly diagnosed patient to screen the thymus: thymoma in 10–15% and hyperplasia in roughly 70% of non-thymomatous cases. Thymoma can extend into pericardium, pleura, or beyond, and its presence mandates removal.
Workup sequence in practice
- Bedside fatiguing manoeuvres once fatigable, fluctuating weakness is suspected.
- The ice pack test when ptosis is present.
- The antibody panel, starting with anti-receptor antibodies.
- Electrodiagnosis to confirm the junction defect.
- Chest imaging for every confirmed case.
Ocular motility documentation, for example with the Lancaster test of gaze positions, records the extraocular pattern in ocular disease.
Evidence anchors
- Gilhus NE, Tzartos S, Evoli A, Palazzo J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primers. 2019;5(1):30. doi:10.1038/s41572-019-0079-y
- Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis. Neurology. 2016;87(4):419-425. doi:10.1212/WNL.0000000000002790
- Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124
- National Institute of Neurological Disorders and Stroke. Myasthenia gravis: https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis