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Autoimmune Dis. 2012; 2012: 874680. Published online 2012 Oct 31. doi: 10.1155/2012/874680
PMCID: PMC3501798PMID: 23193443
Myasthenia Gravis: A Review
Annapurni Jayam Trouth, 1 ,* Alok Dabi, 1 Noha Solieman, 1 Mohankumar Kurukumbi, 1 and Janaki Kalyanam 2
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Abstract
Acquired myasthenia gravis is a relatively uncommon disorder, with prevalence rates that have increased to about 20 per 100,000 in the US population. This autoimmune disease is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. In about two-thirds of the patients, the involvement of extrinsic ocular muscle presents as the initial symptom, usually progressing to involve other bulbar muscles and limb musculature, resulting in generalized myasthenia gravis. Although the cause of the disorder is unknown, the role of circulating antibodies directed against the nicotinic acetylcholine receptor in its pathogenesis is well established. As this disorder is highly treatable, prompt recognition is crucial. During the past decade, significant progress has been made in our understanding of the disease, leading to new treatment modalities and a significant reduction in morbidity and mortality.
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1. Epidemiology
Acquired myasthenia gravis (MG) is a relatively uncommon disorder, with prevalence rates that have increased to about 20 per 100,000 in the US population [1]. This autoimmune disease is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. In about two-thirds of the patients, the involvement of extrinsic ocular muscles (EOMs) presents as the initial symptom, usually progressing to involve other bulbar muscles and limb musculature, resulting in generalized myasthenia gravis (gMG). In about 10% of myasthenia gravis patients, symptoms are limited to EOMs, with the resultant condition called ocular MG (oMG) [2]. Sex and age appear to influence the occurrence of myasthenia gravis. Below 40 years of age, female : male ratio is about 3 : 1; however, between 40 and 50 years as well as during puberty, it is roughly equal. Over 50 years, it occurs more commonly in males [3]. Childhood MG is uncommon in Europe and North America, comprising 10% to 15% of MG cases. In Asian countries though, up to 50% of patients have onset below 15 years of age, mainly with purely ocular manifestations [4].
1.1. Historical Aspect
The first reported case of MG is likely to be that of the Native American Chief Opechancanough, who died in 1664. It was described by historical chroniclers from Virginia as “the excessive fatigue he encountered wrecked his constitutional and work
2. Learning Objectives
• Discuss pathophysiology of Myasthenia Gravis
• Identify clinical features
• Outline treatment options
3.
4. MYASTHENIA GRAVIS
Myo- Muscle Asthenes-weakness gravis- severe
Autoimmune disorder in which antibodies are produced against
body’s own ACh receptor channels on the motor end plate
5. INCIDENCE
• 1 in every 20,000 persons OR
• 25 to 125 of every 1 million people worldwide
• Can occur at any age but seems to have a bimodal distribution;
peak occurrences in individuals in their 20s (mainly women) and 60s
(mainly men)
• Genetic predisposition noted
• The thymus may play a role in the pathogenesis of the disease by supplying
helper T cells sensitized against thymic proteins that cross-react with
acetylcholine receptors
7. Autoimmunity
formation of circulating antibodies against Ach receptor channels
(nicotinic cholinergic receptors) on skeletal muscle (post synaptic
membrane)
body fails to recognize the Ach receptors on skeletal muscle as part
of “self” and attacks them
The antibodies bind to the ACh receptor protein and change it in
some way that causes the muscle cell to pull the receptors out of
the membrane and destroy them.
8. This destruction leaves the muscle with fewer ACh receptors in the
membrane
Plus, AChE destroys much of the ACh before it ever has a chance to
interact with a receptor
Reduced transmission even with normal Ach release from synaptic
terminal to muscle membrane
Reduced EPP- cannot open Na+ channels
The muscle target has a diminished response that is exhibited as
muscle weakness
9.
10.
11. EFFECTS ON MOTOR END PLATE
• The major structural abnormality in myasthenia gravis is the
appearance of sparse, shallow, and abnormally wide or absent
neural/synaptic clefts in the motor endplate.
• The postsynaptic membrane has a reduced response to
acetylcholine
• 70–90% decrease in the number of receptors per endplate in
affected muscles
15. • Serious and often fatal disease
• Skeletal muscles are weak and tire easily (fatigue)- generalized
weakness
• Affect on extraocular muscles leads to ptosis (drooping of eyelids),
diplopia
• Dysphagia
• Dysarthria
In severe cases, affects respiratory muscles including diaphragm leading
to respiratory failure/paralysis and death
19. Currently medical science does not have a cure for myasthenia gravis,
although various drugs can help control its symptoms
Acetyl-cholinestrase (AChE) inhibitor drugs- neostigmine or pyridostigmine
allows larger than normal amounts of acetylcholine to accumulate in the
synaptic space.
• Immunosuppressive drugs (eg, prednisone, azathioprine, or cyclosporine)
can suppress antibody production
• Thymectomy is indicated especially if a thymoma is suspected
