Chronic auto-immune disorder of the post-synaptic membrane at the neuromuscular junction (NMJ) in skeletal muscle
Circulating antibodies against the nicotinic acetylcholine receptor (AchR) and associated proteins impair neuromuscular transmission
Patients present with muscle weakness which typically worsens with continued activity (fatigue) and improves on rest
Severity varies from isolated eye muscle weakness to generalised muscle weakness and respiratory failure requiring mechanical ventilation
Ages 20 – 40
Familial myasthenia gravis
D-penicillamine ingestion (drug-induced myasthenia)
Having other autoimmune diseases
Prominent proximal leg and arm weakness accompanied by diminished muscle stretch reflexes that improve with brief exercise.
Autonomic symptoms such as dry mouth, constipation and impotence are present in some patients.
Eye muscles are occasionally involved at presentation.
Respiratory failure is uncommon.
Associated with small-cell lung cancer in up to 70% of patients.
Symptoms similar to myasthenia gravis (MG) but there may be hypotension, bradycardia, diarrhoea followed by constipation, and urinary retention.
Penicillamine-induced myasthenia gravis
Symptoms similar to MG can occur after weeks or months of treatment
They may remit on withdrawal of the drug; recovery may be slow or incomplete
Gradually progressive muscle weakness which is not fatigable.
These include auto-immune inflammatory myopathies or heritable myopathies as in mitochondrial diseases, such as progressive external ophthalmoplegia, or oculopharyngeal muscular dystrophy (OPMD).
Positive family history
Uncommon disease with an estimated worldwide prevalence of 100 to 200 per million population. 
While MG reportedly occurs in all ethnic groups, relative differences in disease prevalence are yet to be determined.
The disease is manifest from infancy to old age and can occur in both genders although more women than men are affected. 
Women usually present during childbearing age.
Men typically develop symptoms at a later age with a median age of onset in the seventh decade.
It appears that the prevalence of MG is on the increase, particularly in developed countries.
This may be, in part, due to an ageing population, improved longevity of MG patients and availability of more accurate diagnostic tools.
The subset of MG with antibodies directed against muscle tyrosine kinase (MuSK) predominantly affects women (between 80% to 90% of patients)
The incidence is significantly higher in black women, particularly in the US, and the average age at symptom onset is in the mid-30s; earlier than that in non-MuSK MG. 
Several lines of evidence suggest that myasthenia gravis (MG) is an organ-specific, antibody-mediated auto-immune disease.
Antibodies are present at the neuromuscular junction (NMJ), the site of pathology. 
About 80% to 90% of patients have detectable antibodies against the nicotinic acetylcholine receptor (AchR) on the post-synaptic muscle membrane at the NMJ.
Another 3% to 7% of patients have antibodies directed against muscle tyrosine kinase (MuSK), another NMJ protein.
Passive transfer of AchR antibodies from experimental rodents or immunoglobulins from patients with MG causes symptoms similar to MG in rodents. 
Furthermore, immunisation with AchR reproduces MG in experimental animals. 
The aetiology for the synthesis of auto-immune antibodies remains unclear
Certain genotypes, particularly linked to the HLA complex, may be more susceptible. 
Also, the thymus may be involved.
MG is associated with thymic follicular hyperplasia or thymoma in 70% and 10% patients, respectively. 
Thymic myoid cells express AchR and may possibly trigger auto-antibody synthesis.
In contrast in MuSK MG, thymus gland histology is usually normal and thymoma is rare.
The weakness worsens with activity (fatigue) and improves on rest and the fluctuations show diurnal variation (better in morning than in the evening)
Drooping eyelids and double vision occur early in the majority of patients. 
The pupils are spared.
Cooling of eyelid for at least 2 minutes with an ice pack (ice test) improves ptosis in more than 95% of patients with myasthenia gravis (MG).
It does not improve severe ptosis
Double vision occurs early in the majority of patients. 
Difficulties in chewing or swallowing occur when the facial and oropharyngeal muscles are affected
Changes in speech occur when the oropharyngeal muscles are affected and there may be a characteristic nasal speech
Changes in expression occur when the facial muscles are affected and there may be a characteristic flattened smile
Proximal limb weakness
Difficulty in getting out of chairs or climbing stairs.
There is no evident muscle wasting.
Reflexes are normal.
Sensations are intact
Shortness of breath
If shortness of breath becomes severe enough to require mechanical ventilation, the patient is said to be in MG crisis
In myasthenia gravis (MG), an auto-immune attack against acetylcholine receptors (AchRs) results in destruction of the post-synaptic membrane. 
The reduced number of available binding sites for acetylcholine leads to inconsistent generation of muscle fibre action potentials which manifest as skeletal muscle weakness.
Muscle tyrosine kinase (MuSK) is an agrin dependent protein on muscle membrane with an essential role in anchoring AchR at the tips of the postsynaptic folds
Serum anti-acetylcholine receptor (anti-AchR) antibody analysis
Antibodies are detectable in 80% to 90% of patients with generalised myasthenia gravis (MG) and up to 50% of patients with ocular MG. 
Sensitivity: greater than 90% in generalised MG; 40% to 60% in ocular MG.
If the result is negative or equivocal proceed to antimuscle tyrosine kinase (MuSK) antibody assay
Antimuscle tyrosine kinase (MuSK) antibodies
Serial pulmonary function tests
Indicated if shortness of breath and suspected MG crisis.
Serial measurements of FVC and negative inspiratory force (NIF) are taken.
Indication for mechanical ventilation includes FVC 15 mL/kg or less (normal ≥60 mL/kg) and NIF 20 cm H2O or less (normal ≥70 cm H2O).
Physicians should not wait for abnormal ABG as it occurs late in the course after clinical decompensation
This test is not done routinely in all patients
These antibodies are rare in patients without thymoma.
Detected in 75% to 95% of patients with thymoma and MG
Repetitive nerve stimulation
Sensitivity, 79% in generalised MG, 50% in ocular MG.
Specificity, 97%. 
Brief exercise of a muscle prior to the test may enhance decrement response.
If the result is negative and clinical suspicion is high, proceed to single fibre EMG.
Positive decrement also seen in Lambert-Eaton myasthenic syndrome (LEMS) and amyotrophic lateral sclerosis (ALS).
In MuSK MG, generally the yield of abnormal result is high in proximal muscles, for example the trapezius, deltoid and facial muscles.
For patients with neck and respiratory weakness, it is important to evaluate clinically affected muscles as the test may be normal in limb and face muscles. 
Greater than 10% decline in compound muscle action potential (CMAP) amplitude between the first and fourth potential in a train of 10 stimulations of the motor nerve at 2 to 3 Hz is considered a positive response
Sensitivity, 86% to 92% and specificity, 70% to 96% in facial muscles in ocular MG;
Sensitivity and specificity, 98% in generalised MG. 
Abnormal test may be seen in LEMS and ALS, inflammatory myopathies, or patients injected with botulinum toxin.
Increase variability in motor latencies (jitter) or complete failure of neuromuscular transmission (block) in some muscle fibres
CT of chest
Should be performed in all newly diagnosed patients to detect thymoma (which occurs in about 15% of patients with MG) or thymic hyperplasia (which occurs in 75% of MG patients)
Includes DVT prophylaxis; ulcer prophylaxis; adequate nutrition and hydration; and avoidance of infections and drugs that may worsen myasthenia symptoms.
Plasma exchange or intravenous immunoglobulin
Acute therapy for the recovery of transmission across neuromuscular junction
Plasma exchange has rapid response with onset usually after 2 to 3 sessions.
Effects are temporary, lasting weeks.
Therapy is expensive and requires hospitalisation.
Intravenous immunoglobulin (IVIG) is easy to administer but expensive
When patients respond, the onset is rapid within 4 to 5 days with maximal response apparent within 1 to 2 weeks
In patients with muscle tyrosine kinase (MuSK) MG, plasma exchange and immunoglobulin are used during acute exacerbations and crises.
Observational studies indicate plasma exchange to be more effective than immunoglobulin. 
Patients with frequent symptoms should be treated with a cholinesterase inhibitor.
In patients with muscle tyrosine kinase (MuSK) MG, clinical response to cholinesterase inhibitor therapy is generally less favourable
Frequent muscarinic and nicotinic side effects, and sometimes even worsening of symptoms.
Despite this poor response, most patients receive pyridostigmine due to its low side effect profile and low cost
Corticosteroids are used in older men with ocular myasthenia gravis (MG) and those with mild disease who fail pyridostigmine monotherapy
Several options are available and include low-dose corticosteroids, azathioprine, mycophenolate mofetil, ciclosporin and tacrolimus
It is prudent to begin therapy with low dose and gradually titrate up towards maximum dose
High doses can induce worsening of MG symptoms, including precipitating a myasthenic crisis.
Immunotherapy is tailored for each patient, including time to onset of response, adverse effect profile, availability and cost
Tacrolimus is generally better tolerated than ciclosporin. 
Intubation and mechanical ventilation
Indication for mechanical ventilation includes FVC 15 mL/kg or less (normal ≥60 mL/kg) and negative inspiratory force (NIF) 20 cm H2O or less (normal ≥70 cm H2O)
Some patients may require a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube. 
Performed in patients with thymoma (any age) or without thymoma (15 to 55 years old). 
Approaches available include robotic thoracotomy, transcervical or full sternotomy.
It is generally accepted that more complete the removal of thymus, higher is the rate of remission in MG symptoms.
Onset of benefit is delayed, rarely seen within 6 months and requires follow-up of up to 2 to 5 years for demonstrated efficacy.
The role of thymectomy for patients with muscle tyrosine kinase (MuSK) MG remains uncertain in the absence of a controlled trial.
Symptomatic improvement and clinical remission are the goals of therapy.
However, the onset of improvement varies greatly from days to months.
Typically, older men with ocular complaints respond promptly to corticosteroid monotherapy whereas generalised symptoms are slower to respond and require more aggressive therapy.
Chronic maintenance drug therapy is often required.
Disease exacerbations can occur due to infections, surgery, medicine exposures, malignancy, pregnancy or other stressors.
Myasthenic crisis can sometimes be averted with aggressive early intervention during an exacerbation.
Most patients enjoy good quality of life and normal lifespan due to advances in diagnosis and immunosuppressive treatment.