- Clinical science
Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by generalized muscle weakness. The pathophysiology of MG involves autoantibodies directed against postsynaptic acetylcholine receptors (AchR), thereby impairing neuromuscular transmission. Women are more frequently affected and about 10–15% of cases are associated with thymoma. The most common initial symptoms are ptosis and/or diplopia due to ocular muscle weakness, with the disease usually progressing to generalized weakness within two years. At that point, patients have difficulties standing up, climbing stairs, and possibly even swallowing and/or chewing. Muscle weakness worsens throughout the day with increased activity and improves after rest. MG is diagnosed according to patient history, physical examination, antibody testing, and electromyographic evaluation. All patients should be screened for thymomas via CT as they can be surgically removed, allowing for possible curative treatment. The treatment of choice consists of acetylcholinesterase inhibitors, possibly in combination with immunosuppressive drugs if symptoms persist. Acute exacerbations, as seen in myasthenic crisis, should be treated with either IV immunoglobulins or plasma exchange.
- Autoreactive antibodies directed against postsynaptic acetylcholine receptors or receptor-associated proteins
- Association with other autoimmune diseases, including:
Associated conditions 
- Thymoma (the most common primary tumor in the anterior mediastinum) in 10–15% of patients
- Thymic hyperplasia in 65% of patients
- Graft-versus-host reaction after allogeneic stem cell transplantation (especially in children)
Main clinical forms
- Ocular myasthenia: only the extraocular and/or eyelid muscles
- All skeletal muscles may be involved.
- Especially ocular, bulbar, limb, and respiratory muscles
- Muscle-like (myoid) cells in the thymus express AChR → autoreactive targeting by T cells → production of acetylcholine receptor antibodies (AChR antibodies)
- Responsible for inhibition of signal transduction at the neuromuscular junction (NMJ)
- Antibodies target postsynaptic AChRs of normal muscle cells → competitive inhibition of acetylcholine (ACh) → AChR decay through receptor internalization (↓ receptor density at the postsynaptic membrane) and activation of complement (→ muscle cell lysis) → impaired signal transduction at the NMJ → skeletal muscle weakness and fatigue
- Symptoms worsen with increased muscle use throughout the day and improve with rest.
- Sometimes associated with exacerbating factors, including:
Clinical manifestations 
Fatigable weakness of skeletal muscles in which smaller muscles responsible for fine movements (e.g., eye muscles) tend to be affected first, while larger muscles become affected later on.
- Eye muscle weakness: most common initial symptom
- Bulbar muscle weakness
- Proximal limb weakness
- Respiratory muscle weakness: causes dyspnea
Muscle fatigue worsens throughout the day and with increased activity.
- Suspected cases of MG are generally confirmed via EMG and AChR antibodies.
- Chest CT to rule out thymoma
- AChR antibody test (most specific test)
- Other associated antibodies: anti-MuSK
- Chest CT: every newly diagnosed MG patient to rule out thymoma
- Edrophonium test ( )
- Simpson test
- Ice test: ice pack placed on one eye for 5 minutes → temporary improvement of eyelid fatigue
- Definition: rare autoimmune disease that reduces neuromuscular transmission, leading to muscle weakness
- Pathophysiology: autoantibodies directed against presynaptic voltage-gated calcium channels (anti-VGCC antibodies) → ↓ Ca2+ influx → ↓ presynaptic vesicle fusion → impaired acetylcholine release in the NMJ
- Clinical features
- Active muscle contraction or repeated muscle tapping increases reflex activity.
- Lambert sign: physical examination finding in which a patient's muscle strength improves with repetitive or ongoing use (e.g., muscle force gradually increases when a patient with LEMS is asked to squeeze the examiner's hand)
- EMG: Repetitive nerve stimulation results in incremental responses.
- Confirmatory test: serologic detection of anti-VGCC antibodies
- Physical examination
- Treatment 
Comparison of MG and LEMS
|Myasthenia gravis vs. Lambert-Eaton myasthenic syndrome|
|Myasthenia gravis||Lambert-Eaton myasthenic syndrome|
|Weakness|| || |
|Reflexes|| || |
|Repetitive nerve stimulation (RNS)|| || |
|Autonomic dysfunction|| || |
|Response to cholinesterase inhibitors|| || |
Other differential diagnoses
- Congenital myasthenic syndrome
- (for ocular symptoms)
The differential diagnoses listed here are not exhaustive.
First line: cholinesterase inhibitors
- Drug of choice: pyridostigmine
- Only improve symptoms (no causal treatment)
- See “.”
- Supplemental immunosuppressants: if symptoms persist despite anticholinesterase treatment
- Definition: acute, life-threatening exacerbation of myasthenic symptoms that leads to respiratory failure
- Affects 15–20% of patients with MG
- Most commonly occurs within 8–12 months after onset
- Surgery, anesthesia
- Differential diagnosis: cholinergic crisis
- IVIg 400mg/kg for 5 days
- Early endotracheal intubation
Differential diagnosis of mysthenic crisis and cholinergic crisis
|Myasthenic crisis vs. cholinergic crisis|
|Fasciculations|| || |
|Skin|| || |
|Bronchial secretion|| || |
We list the most important complications. The selection is not exhaustive.
- The prognosis of ocular MG is good.