From the Guidelines
Myasthenia gravis is an autoimmune disorder characterized by the production of antibodies that attack acetylcholine receptors at the neuromuscular junction, leading to fluctuating muscle weakness and fatigue. The pathophysiology of myasthenia gravis involves the reduction of functional acetylcholine receptors, which impairs the muscle's ability to respond to nerve signals 1. When a nerve impulse reaches the neuromuscular junction, it normally triggers the release of acetylcholine, which binds to receptors on the muscle membrane to initiate muscle contraction. In myasthenia gravis, fewer receptors are available for binding, resulting in inadequate muscle activation and the characteristic symptoms of the disease.
The disease typically affects voluntary muscles, particularly those controlling:
- Eye movements
- Facial expressions
- Chewing
- Swallowing
- Limb movements Symptoms worsen with continued activity and improve with rest, reflecting the progressive depletion and subsequent replenishment of acetylcholine at affected neuromuscular junctions 1. The thymus gland plays a significant role in this disease, as thymic abnormalities (hyperplasia or thymoma) are present in many patients and may contribute to the production of these autoantibodies.
Key Points
- Myasthenia gravis is an autoimmune disorder that affects the neuromuscular junction
- The disease is characterized by fluctuating muscle weakness and fatigue
- The thymus gland plays a significant role in the disease
- Symptoms worsen with continued activity and improve with rest
- Thymectomy is indicated in some cases, always in the presence of thymoma, and may substantially reduce symptoms for certain subpopulations with myasthenia gravis 1.
According to the most recent study 1, the patient population includes adults with myasthenia gravis without geographic or racial predilection, although this disorder occurs in children as well. Patients are at risk for having or developing a thymoma. Recognition of the disorder is crucial to initiate appropriate workup and referral to other subspecialties, including neurology. Ensure proper medical and surgical treatment, and initiate short-term and subsequent long-term management of associated ptosis and strabismus 1.
From the Research
Pathophysiology of Myasthenia Gravis
- Myasthenia gravis is a rare disease that causes impairment of the neuromuscular junction, characterized by muscle weakness and abnormal fatigability 2, 3.
- The disease is caused by the presence of antibodies against components of the muscle membrane localized at the neuromuscular junction, with the acetylcholine receptor (AChR) being the most common target 2, 3, 4.
- Other targets of autoantibodies in myasthenia gravis include the MuSK protein (muscle-specific kinase) and the LRP4 (lipoprotein related protein 4) 3, 4.
- The presence of a high number of long-lived plasma cells in myasthenia gravis patients contributes to the perpetuation of the autoimmune response, and treatments targeting these cells, such as proteasome inhibitors, have shown promise in experimental models 2.
Clinical Features and Classification
- Myasthenia gravis can be classified according to the profile of autoantibodies, the location of affected muscles, the age of onset of symptoms, and thymic abnormalities 3, 4.
- The disease typically begins with ocular symptoms, such as ptosis and diplopia, and may extend to other muscles in 80% of cases 3.
- Other clinical features of myasthenia gravis include variability, effort-induced worsening, and successive periods of exacerbation, with severity dependent on respiratory and swallowing impairment 3, 4.
Diagnosis and Treatment
- Diagnosis of myasthenia gravis is based on clinical features, the benefit of cholinesterase inhibitors, detection of specific autoantibodies, and significant decrement evidenced by electrophysiological tests 3, 4.
- Treatment options for myasthenia gravis include symptomatic treatment, immunosuppressive treatment, and thymectomy, with advances in understanding the pathophysiology leading to new treatment options targeting B or T cells, the complement cascade, and cytokines 5, 4.
- Despite available treatments, a large proportion of patients remain chronically dependent on corticosteroids, highlighting the need for more personalized and effective treatment approaches 4.