Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating weakness in voluntary muscles. This condition occurs when the immune system mistakenly produces antibodies that attack the neuromuscular junction, the communication point between nerves and muscles. While MG often begins with weakness in the eyes or face, it can progress to involve generalized body muscles. Although modern treatments have improved the prognosis, MG remains serious due to the potential for sudden, severe complications that can quickly become life-threatening. Careful monitoring and prompt intervention are necessary for long-term survival.
Myasthenic Crisis and Respiratory Failure
The most common cause of death directly attributable to myasthenia gravis is respiratory failure, resulting from a Myasthenic Crisis (MC). An MC is a life-threatening complication where muscle weakness compromises the patient’s ability to breathe adequately, often requiring mechanical ventilation. Up to 20% of people with MG experience at least one Myasthenic Crisis, typically within the first few years after diagnosis. While historical mortality rates were high, the fatality rate today is generally between 4% and 10% when patients receive prompt and appropriate treatment.
Mechanism of Respiratory Compromise
Respiratory failure during a Myasthenic Crisis is caused by profound weakness of the muscles responsible for moving air in and out of the lungs. The diaphragm, the primary muscle of breathing, and the intercostal muscles become too weak to perform inspiration and expiration, leading to insufficient air exchange.
A second dangerous mechanism involves weakness in the bulbar muscles, which control the throat, tongue, and jaw. Bulbar weakness can obstruct the upper airway and causes dysphagia (difficulty swallowing) and an impaired cough reflex.
This poor control increases the risk of aspiration, where food, liquid, or saliva enters the lungs. Subsequent aspiration pneumonia introduces a severe infection, placing an overwhelming burden on the compromised respiratory system. The combination of weak breathing muscles, infection, and aspiration is the physiological pathway leading to a fatal outcome.
Modern Mortality Rates and Prognosis
While a Myasthenic Crisis remains the primary cause of death, the overall mortality rate for people with MG is now low, with most individuals having a near-normal life expectancy. Overall in-hospital mortality is estimated to be around 2.2%, rising to 4.5% to 10% during an acute crisis. This low rate reflects significant advancements in treatment and critical care management.
However, certain factors are associated with a higher mortality risk. These factors include being male, having an older age of onset (particularly after 50 years old), and having a thymoma (a tumor of the thymus gland). The risk of death is also heightened by delayed diagnosis or treatment, or when a crisis is triggered by certain medications or a severe infection.
Preventing Fatal Outcomes
Preventing a fatal outcome requires recognizing the early warning signs of an impending Myasthenic Crisis and ensuring swift medical intervention. Key warning signs include increasing difficulty swallowing, a change in voice quality (becoming nasal or slurred), and a weak, ineffective cough. Patients should also monitor for shortness of breath, shallow breathing, or nasal regurgitation of fluids while drinking.
Any rapid worsening of symptoms requires immediate emergency medical attention before respiratory muscles fail completely. In the hospital setting, immediate life-saving treatments include respiratory support, such as mechanical ventilation.
Specialized immunotherapies are then administered to rapidly reduce harmful autoantibodies in the bloodstream. These treatments typically involve plasma exchange, which filters the antibodies from the blood, or high-dose intravenous immunoglobulin (IVIg). Long-term prevention relies on strict adherence to the prescribed daily medication regimen, like anticholinesterase inhibitors, and avoiding known crisis triggers, such as respiratory infections or certain antibiotics.