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.
Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) share the symptom of weakness but differ in almost every other respect. One anatomical fact organises the whole comparison: MG attacks the postsynaptic muscle endplate, while LEMS attacks the presynaptic nerve terminal. Every clinical difference below flows from that single distinction (Titulaer et al., 2011).
Head-to-head comparison
| Feature | Myasthenia gravis | Lambert-Eaton myasthenic syndrome |
|---|---|---|
| Antibody target | Postsynaptic acetylcholine receptor (or MuSK/LRP4) | Presynaptic voltage-gated calcium channels |
| Mechanism | Fewer working receptors, so each signal answers less | Less calcium entry, so less acetylcholine released per signal |
| Ocular involvement | Common and often the first sign (ptosis, diplopia) | Usually spared |
| Weakness pattern | Ocular, then bulbar, then proximal limbs | Proximal limbs, legs more than arms; bulbar less prominent |
| Reflexes | Normal | Absent or reduced, sometimes normalising briefly after exercise |
| Exercise effect | Worsens with sustained activity (fatigability) | Improves briefly with repeated effort (facilitation) |
| Autonomic symptoms | Rare | Common: dry mouth, constipation, erectile dysfunction, orthostatic hypotension |
| Age and sex pattern | Bimodal: young women and older men | Slight male predominance; median onset around 60 |
| Tumour association | Thymoma in 10–15%; thymic hyperplasia in about 70% of the rest | Small cell lung carcinoma in roughly half; neurology may precede the cancer by months to years |
| Electrodiagnosis | Decremental response on slow repetitive stimulation (over 10% fall) | Incremental response on rapid stimulation or after exercise (over 100% growth) |
| Acetylcholinesterase inhibitor response | Good; pyridostigmine is first-line | Poor; more transmitter cannot fix a release defect |
| First-line treatment | Pyridostigmine, then steroids, azathioprine, thymectomy | 3,4-diaminopyridine plus treatment of the underlying lung tumour |
Why exercise helps one and harms the other
In LEMS, antibodies destroy presynaptic calcium channels, so a single impulse admits too little calcium and releases too little transmitter. With repeated impulses, calcium accumulates in the terminal faster than it clears, partially compensating for the missing channels and transiently improving strength. That residual-calcium logic is the shared basis of clinical facilitation and the electrical incremental response. In MG no such compensation exists: with fewer receptors available, repeated signalling only depletes the remaining reserve further, so weakness deepens with use.
Approaching proximal weakness at the bedside
When the presentation is proximal limb weakness, six checks separate the two:
- Reflex behaviour, including whether reflexes recover after brief exercise.
- Autonomic symptoms.
- Early and prominent ocular signs, which favour MG.
- Smoking history and lung-cancer risk, which favour LEMS.
- The stimulation response.
- Mandatory chest imaging with calcium-channel antibody testing and ongoing cancer surveillance when LEMS is suspected.
Proximal weakness with absent reflexes should always raise LEMS and trigger the malignancy search, since finding the tumour early can be life-saving.
A third junction-adjacent disorder completes the landscape by contrast: neuromyotonia (Isaacs syndrome), driven by potassium-channel antibodies of the peripheral nerve, produces continuous muscle overactivity with cramps and stiffness rather than weakness at all.
Evidence anchors
- Titulaer MJ, Lang B, Verschuuren JJGM. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10(12):1098-1107. doi:10.1016/S1474-4422(11)70245-9
- 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