Myasthenia Gravis

September 17, 2011

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction (NMJ) that results in muscle weakness and fatigability. Muscle contractions occur when electrical impulses travel along motor nerve fibers and end at the neuromuscular junction. When an electrical impulse reaches the nerve fiber terminal, it causes the release of a molecule called acetylcholine (ACh). Acetylcholine diffuses across the gap (neuromuscular junction) and activates specialized Acetylcholine receptors (AcetylcholineR) on the muscle fiber. Acetylcholine receptors activation causes electrical activation of muscle fibers and contraction. Excess Acetylcholine in the neuromuscular junction is eliminated by an enzyme called cholin esterase (ChE). In Myasthenia gravis, there are circulating antibodies directed against Acetylcholine receptors. These attach and cause elimination of Acetylcholine receptors. With a paucity of Acetylcholine receptors, there is failure of nerve-to-muscle transmission, especially high levels of activity. This presents as fatigability or muscle weakness with repeated contraction. Muscles around the eye and muscles of the face and throat are particularly vulnerable in Myasthenia gravis.

The prevalence of Myasthenia gravis is about 150 per million. Onset is early in women (late teens and 20s) and late in men (60s and 70s). Prevalence used to be higher in women, but with the aging of the population, may be higher in men now. Ten percent of patients with Myasthenia gravis have a tumor of the thymus gland (thymoma) in the chest. In others, there may be enlargement of the thymus (hyperplasia).

Myasthenia gravis manifests as waxing and waning drooping of eyelids; double vision or squint; facial weakness and loss of expression; weakness/fatigability of chewing, swallowing, and speech; neck weakness; weakness/ fatigability of arm and leg muscles; and weakness of breathing muscles in varying combinations. Prolonged activity worsens symptoms. Examples are double vision while reading or watching television, voice slurring during a long conversation, chewing or swallowing difficulty as the meal progresses, or hands getting weak with repeated activity. Symptoms are commonly worse in the evenings than in the mornings. If weakness is restricted to the muscles around the eyes, the disorder is termed ocular Myasthenia gravis. More commonly, it is diffuse and is called generalized Myasthenia gravis. Generalized Myasthenia gravis can be mild or can be severe. Acute severe worsening of Myasthenia gravis (myasthenic crisis) may be precipitated by infection, surgery, or some medications. Weakness of breathing muscles during a myasthenic crisis may necessitate ventilatory support.

Often, Myasthenia gravis starts around the eyes and becomes generalized in ensuring months. Infrequently, Myasthenia gravis spares the eye and face muscles. Myasthenia gravis is usually a lifelong problem. Most of the worsening and fluctuation in severity is seen in the first few years of the disease. After several years, the disease tends to stabilize, but there may be some residual fatigability and weakness. Most myasthenics receiving appropriate medical care can remain independent and lead productive lives.

The diagnosis of Myasthenia gravis is challenging, and clinical suspicion needs to be high. If Myasthenia gravis is suspected, a bedside test (Tensilon® test) which assesses transient improvement after injection of edrophonium may be performed. Often, the physiological change in neuromuscular junction transmission can be demonstrated by a decrement in muscle response on repetitive electrical stimulation of nerve. The most sensitive test for Myasthenia gravis is an electrical test called single fiber EMyasthenia gravis. A blood test for the detection of Acetylcholine receptors antibodies is quite sensitive and specific.

Treatment options include cholin esterase inhibitors (such as pyridostigmine and neostigmine, which increase availability of Acetylcholine by blocking its destruction), corticosteroids (which reduce the autoimmune response), and azathioprine and other immunosuppressants. Most experts believe that removal of the thymus gland (thymectomy) early in the course of generalized Myasthenia gravis improves the longterm course. In periods of acute worsening, removal of antibodies from the blood (plasma exchange) can rapidly improve symptoms. Intravenous immunoglobulin is also an option for acute worsening. Several classes of medications, especially anesthetic agents, some cardiac medications, and some antibiotics can cause worsening of Myasthenia gravis and need to be avoided.

Pregnancy has special implications for myasthenics. About one third get worse during pregnancy or after delivery. Weakness of muscles may make vaginal delivery difficult. About 10-20% of infants born to myasthenic mothers may have transient weakness and trouble feeding for the first few weeks after birth (neonatal myasthenia) because of antibodies crossing the placenta.

Myasthenia gravis is not a genetic disease. Rarely, disorders closely resembling Myasthenia gravis are seen running in families. Such congenital myasthenic syndromes are not autoimmune; rather, they are genetic defects in proteins of the neuromuscular junction. Some other disorders of the neuromuscular junction of note that have only a passing similarity to Myasthenia gravis are Lambert-Eaton myasthenic syndrome and botulism.

SEE ALSO: Autoimmune disorders, Pregnancy

Suggested Reading

  • Engel, A. (Ed.). (1999). Myasthenia gravis and myasthenic syndromes (Contemporary neurology series, no. 56). New York: Oxford University Press.
  • Richman, D. P. (Ed.). (1998). Myasthenia gravis and related diseases: Disorders of the neuromuscular junction. Annals of the New York Academy of Sciences, 841, 1—831.
  • Vincent, A., Palace, J., & Hilton-Jones, D. (2001). Myasthenia gravis. Lancet, 357, 2122-2128.


Category: M