Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) characterized by muscle weakness that worsens with activity and improves with rest. MG is caused by autoantibodies directed against postsynaptic molecules, most commonly acetylcholine receptors (AchR), resulting in impaired neuromuscular transmission. Women are more frequently affected; ∼ 10–15% of cases are associated with thymoma. The most common initial symptom is ocular muscle weakness (e.g., ptosis and/or diplopia), with progression to generalized weakness typically occurring within two years. The diagnosis is clinical and confirmed by antibody testing and electromyographic evaluation. Treatment of choice consists of acetylcholinesterase inhibitors; immunosuppressive drugs can be added if symptoms persist. All patients with MG should be screened for thymoma with CT chest. Thymectomy is indicated for patients with confirmed thymoma. Acute exacerbations, as seen in myasthenic crises, are generally treated with either IV immunoglobulins or plasma exchange.
- Autoantibodies directed against postsynaptic acetylcholine receptors or receptor-associated proteins
- Association with other autoimmune diseases, including:
Associated conditions 
- Muscle-like (myoid) cells in the thymus express AChR → autoreactive targeting by T cells → production of acetylcholine receptor antibodies (AChR antibodies)
Acetylcholine receptor 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
Severity typically varies during the day and from day to day
- Fatigable weakness of skeletal muscles that worsens with increased muscle use and improves with rest.
- Generalized disease can involve all skeletal muscles, especially:
- Localized disease most commonly affects the eye muscles.
Eye muscle involvement is the most common initial symptom in generalized disease; larger muscles are involved later in the disease course. 
Physical examination findings 
Physical examination may be completely normal in patients with myasthenia gravis, especially in mild cases.
- Normal deep tendon reflexes
- Limb weakness is typically symmetrical.
- Ocular weakness (e.g., ptosis) is typically asymmetrical. 
- Examination and proactive maneuvers can elicit typical ocular findings. 
- The eyebrow of the unaffected eye is usually lower than the affected eyebrow. 
- Ice-pack test: An ice pack placed on the affected eyelid for 5 minutes improves ptosis by ≥ 2 mm. 
- Curtain sign: Lifting the more ptotic eyelid worsens ptosis in the contralateral eyelid; eyebrow elevation and furrowing of the forehead can also occur.
- Cogan lid twitch sign: brief eyelid twitching when looking straight ahead after 10–20 seconds of downward gaze 
- Simpson test: historically used to reproduce eyelid fatigue; positive if looking upward for > 1 minute (without lifting the head) provokes eyelid fatigue
Exacerbating factors of myasthenia gravis 
The following factors may worsen symptoms of MG and/or trigger a myasthenic crisis.
Laboratory studies 
Results can confirm the diagnosis and be used to classify MG into subgroups depending on the antibody profile.
- Initial test: anti-AChR antibodies (highly specific for MG) 
- Subsequent tests
Additional studies 
- EMG of affected muscles ; 
- Chest CT: indicated in all patients with confirmed myasthenia gravis to assess for a thymoma or thymic hyperplasia
- Edrophonium test: administration of a rapid-acting, short-duration acetylcholinesterase inhibitor to assess for symptom improvement in patients with suspected myasthenia gravis
Lambert-Eaton myasthenic syndrome (LEMS) 
- Definition: rare neuromuscular junction disorder characterized by proximal muscle weakness and autonomic dysfunction
- 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: hand grip strength gradually increases over several seconds 
- EMG: Repetitive nerve stimulation results in incremental responses.
- Confirmatory test: anti-VGCC antibodies in serum
- Other: CT chest, abdomen, and pelvis to screen for underlying malignancy
- Physical examination
- Treatment 
Comparison of Myasthenia gravis and LEMS
|Myasthenia gravis vs. Lambert-Eaton myasthenic syndrome|
|Myasthenia gravis||Lambert-Eaton myasthenic syndrome|
|Weakness|| || |
|Reflexes|| || |
|Repetitive nerve stimulation|| || |
|Autonomic dysfunction|| || |
|Response to cholinesterase inhibitors|| || |
Other differential diagnoses
- Congenital myasthenic syndrome
- (for ocular symptoms)
The differential diagnoses listed here are not exhaustive.
- For patients with MG and difficulty breathing, admit to the hospital to rule out or treat .
- Provide supportive therapy and avoid .
Treatment aims to control symptoms but is not curative.
- Titrate pharmacotherapy to minimize adverse effects, usually in consultation with a neurologist.
- Refer for thymectomy based on disease subtype and adequacy of pharmacological symptom management.
Supportive therapy 
- Provide age-appropriate immunizations; see “Overview of ACIP Immunization Schedule.”
- Encourage low-to-moderate intensity physical activity, and provide .
- Correct visual impairment.
- Educate patients about common fluoroquinolones). (e.g.,
- Cholinesterase inhibitor: first-line agent is pyridostigmine titrated to symptom relief 
- Immunosuppressants (off-label)
Glucocorticoids may be a part of the management of myasthenia gravis; however, caution is required as they have been associated with myasthenic crises in 9–18% of patients, especially within the first two weeks of initiating treatment. 
- Consider for:
- Potential benefits include:
- Reduced symptoms and exacerbations
- Decreased doses of pharmacotherapy
Patients with rare subtypes of MG (e.g., MuSK-Ab) generally do not benefit from thymectomy. 
Myasthenic crisis 
- Definition: acute, life-threatening exacerbation of myasthenic symptoms that leads to respiratory failure
- Affects 15–20% of patients with myasthenia gravis 
- Most commonly occurs within 3 years of disease onset 
- Precipitating factors: unidentifiable in up to 50% of cases 
- Differential diagnosis: due to an excessive dose of acetylcholinesterase inhibitors (very rare) 
Management: Treat as a life-threatening emergency in consultation with neurology and critical care. 
- Consider serial spirometry and testing.
- Intubate early if risk of respiratory failure is high, e.g.: 
- Follow .
- Review new medications; consider stopping known . 
- Consider pharmacotherapy with specialist guidance.
Differential diagnosis of myasthenic 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.
- Without treatment: up to 30%
- With treatment: less than 5%
Special patient groups
Myasthenia gravis during pregnancy 
- Risk of developing myasthenia gravis is increased in pregnant and postpartum individuals.
- Myasthenic symptoms often worsen during pregnancy, most commonly during the first trimester.
- Pregnant individuals are at increased risk of myasthenic crisis.
- Cesarean sections are commonly required for pregnant patients with MG because of ineffective contractions due to muscle weakness and risk of exhaustion during vaginal delivery.
- In about 10% of cases, newborns develop transient neonatal myasthenia (due to the transfer of maternal antibodies), which usually manifests with swallowing and sucking difficulties.