This resource has been developed by Alexion, AstraZeneca Rare Disease.
Generalised myasthenia gravis (gMG) is a chronic, fluctuating, antibody-mediated autoimmune disorder in which autoantibodies are directed against the acetylcholine receptors (AChRs) located on the neuromuscular junctions of skeletal muscles. It results in a wide spectrum of symptoms, such as mild ptosis and ocular symptoms to profound bulbar, limb and respiratory muscle weakness, which range from mild to potentially fatal.1
A myasthenic crisis is an acute exacerbation of gMG that is potentially life threatening.2 Characteristic symptoms are extensive weakness, dysphagia and dyspnoea which can result in respiratory insufficiency.2 Respiratory insufficiency is often the result of respiratory muscle weakness but can also be due to bulbar weakness with upper airway collapse.3
A myasthenic crisis usually occurs during the first 2–3 years of the disease course in approximately 15%–20% of patients.3 Elderly patients aged approximately 60–70 years are more likely to have a myasthenic crisis than younger patients.3
A myasthenic crisis usually occurs during the first 2–3 years of the disease course in approximately 15%–20% of patients.3 Elderly patients aged approximately 60–70 years are more likely to have a myasthenic crisis than younger patients.3
Respiratory insufficiency requires the use of invasive or non-invasive ventilation.3 Prompt treatment of a myasthenic crisis is potentially lifesaving. All myasthenic patients with questionable respiratory status should be admitted to an intensive care unit.3
The aims of treatment of a myasthenic crisis are:3
The aims of treatment of a myasthenic crisis are:3
- Immediate management of airway, respiratory and circulatory support
- Confirmation of the diagnoses of myasthenic crisis
- Evaluation and treatment of acute respiratory failure
- Identification and elimination of potential precipitating factors
- Initiation and adjustment of immunomodulatory treatment
- Prevention and treatment of complications
- Aseptic and soft suctioning
- Aggressive respiratory therapy including intermittent positive pressure breathing, sigh exercise, cough augmentation, and chest physiotherapy Bronchodilators
- Humidification of inspired gas to thin secretions
- Early placement of feeding tubes and maintenance of caloric intake at approximately 25–35 calories/kg, low carbohydrate feeds to reduce hypercarbia
- Maintenance of electrolyte balance (avoid over-correcting hypomagnesaemia)
- Treatment of anaemia: transfuse when haematocrit values are <30%
- Prophylaxis of deep-vein thrombosis with compression and/or heparinoids
- Hemodynamic stability and continuous cardiac monitoring
- Aggressive treatment of fever and infection with antibiotics
- Optimal pain management
- Disease modifying treatments, e.g. IVIG, plasmapheresis or corticosteroids
Signs of a myasthenic crisis should be investigated and monitored in gMG patients with significant limb weakness even without dyspnoea.3 gMG patients with significant bulbar weakness may present with limited limb and respiratory weakness but can quickly evolve to a myasthenic crisis due to collapse of the upper airway and/or aspiration.3 Some patients may present with respiratory insufficiency without significant limb or bulbar weakness.3
Clinical features include ocular, orofacial, bulbar, neck and respiratory muscle weakness; ophthalmoparesis and ptosis are frequently seen.3
The most reliable sign of impending respiratory failure is the presence of a paradoxical breathing pattern, i.e., inward rather than outward movement of the abdomen with each inspiration, and shallow chest expansion due to diaphragm muscle weakness.3
Clinical features include ocular, orofacial, bulbar, neck and respiratory muscle weakness; ophthalmoparesis and ptosis are frequently seen.3
The most reliable sign of impending respiratory failure is the presence of a paradoxical breathing pattern, i.e., inward rather than outward movement of the abdomen with each inspiration, and shallow chest expansion due to diaphragm muscle weakness.3
Common risk factors for a myasthenic crisis are shown in the table.