A collaborative approach to myasthenia gravis

A collaborative approach to myasthenia gravis
A collaborative approach to myasthenia gravis


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Myasthenia gravis (MG) is a chronic neurologic disease and the most common disease of neuromuscular transmission. Although neurologists should be involved in the care of these patients, diagnosis often begins at the primary-care level.

To prevent delay in diagnosis, primary-care providers (PCPs) must understand variations in the presentation of MG as well as basic diagnostic tools. Knowledge of treatment of the disorder and an understanding of some of the challenges people with MG face allows the PCP to work in synergy with the neurologist to provide a more comprehensive health plan.


Overview


Acquired MG is an immunologic disorder in which antibodies are directed against the postsynaptic (muscle) nicotinic acetylcholine receptor (AChR). The anti-AChR antibodies reduce the number of available AChRs at neuromuscular junctions via three means: (1) accelerating turnover of AChRs through a mechanism involving cross-linking and rapid endocytosis of the receptors; (2) damage to the postsynaptic muscular membrane by the antibody in collaboration with complement; and (3) blockage of the active site of the AChR, where acetylcholine normally binds.1

Despite the normal release of acetylcholine by the presynaptic membrane, patients experience weakness because there is a smaller probability a nerve impulse will generate a muscle action potential.2 A presentation of fatigable muscle weakness is the hallmark of MG and occurs as presynaptic vesicles are depleted with sustained activity.2 Weakness can be found in the powerful movements that fatigue easily, external ocular muscles and other cranial muscles (i.e., masticatory, facial, and pharyngeal), and respiratory and limb muscles.3

In addition to anti-AchR antibodies, MG can also result from an immune response to muscle-specific kinase (MuSK)—a protein involved in AChR clustering at neuromuscular junctions—by reducing the number of AChRs.1

At approximately 10 to 15 cases per 100,000 population, the incidence of MG is rare.4 Women are more affected than men overall,1 but acquired MG has a bimodal incidence that peaks in the second and third decades of life (during which time women are more commonly affected) and in the seventh and eighth decades (when men are more commonly affected).2

Approximately 10% of patients with MG have thymic tumors referred to as thymomas.1 Earlier onset MG is often associated with thymic hyperplasia, whereas thymoma is seen more in individuals with later-onset disease.2 Historically, only a small portion of thymomas are malignant.1 Approximately 10% of MG patients have another autoimmune disorder.5 While onset is usually insidious, sudden exacerbation can occur when the disease is unmasked by coincidental infection or stress to the body; exacerbations can also occur before the menstrual period or shortly after pregnancy.3

MG is subject to relapses and remissions and can have such fatal outcomes as respiratory distress from aspiration pneumonia.3 A summary of the key features of MG can be found in Table 1.

Table 1. Key features of myasthenia gravis

Mediated by antibodies directed against the postsynaptic nicotinic ­acetylcholine receptors
Causes fluctuating and fatigable weakness of commonly used voluntary muscles, which produces such symptoms as diplopia, ptosis, dysphagia, difficulties chewing, limb weakness, respiratory complications, or a ­combination of these
Diagnosis can be aided through receptor antibodies, Tensilon test, or electrodiagnostic testing.
Imaging is important to rule out coexisting thymoma.
Treatments includes acetylcholinesterase inhibitors, immunomodulating therapy, and thymectomy.




Clinical presentation and exam findings


Individuals with MG often present with diplopia (double vision), ptosis (droopy eyelid), difficulties in chewing or swallowing, limb weakness, respiratory complications or a combination of these. Some patients may have isolated weakness, such as purely ocular MG, while others may have or later develop generalized weakness.

Symptoms often fluctuate in intensity during the day, but fatigable muscle weakness is characteristic; symptoms also tend to be worse at the end of the day. Such ocular involvement as diplopia and ptosis is most common, followed by bulbar weakness with complaints of dysphagia and dysarthria.2 Limb weakness tends to be proximal and symmetric and should not conform to the distribution of any single nerve, root, or level of the central nervous system.2,6

Most patients have generalized disease, but up to 15% may have limited ocular disease.2 MG involves the ocular muscles in approximately 90% of patients, and more than 60% present with ocular involvement.6 In 85% of patients, weakness becomes generalized, affecting the limb muscles as well; weakness that remains restricted to the extraocular muscles for three years is unlikely to become generalized, and these patients are said to have ocular MG.1

There are no factors that predict which individuals who present with ocular disease will generalize.7 Bulbar weakness is especially prominent in MuSK-antibody-positive MG.1 Less common presentations include isolated neck weakness, isolated respiratory muscle weakness, and distal limb weakness.7    

The examination for an individual with suspected MG is directed at demonstrating weakness and fatigability. Ask the patient to sustain a gaze or limb posture for a few minutes and to follow it with a brief period of exercise or repetitive muscle activity (Table 2).

Table 2. Myasthenia gravis physical exam findings1-4,6,7,13

Ocular – 50% to 60% present with ocular ­complaints; about half of these patients will develop generalized disease within two years. Many who present without ocular complaints develop ­diplopia/ptosis at some point
  • Pupillary responses should be normal.
  • Ptosis, ocular palsies (often asymmetric)
  • Eyelid may show a characteristic twitch.
  • Sustained upgaze for two minutes can lead to increased ptosis, which improves after rest.
  • Binocular diplopia, which results from misalignment of eyes (diplopia should disappear when
  • either eye is covered)
  • Curtain sign
Bulbar – about 15% present with bulbar symptoms
  • Patient may demonstrate weakness with dysarthria, dysphagia, fatigable chewing.
  • Speech may have a nasal timbre, caused by weakness of the palate.
Limb – less than 5% present with proximal leg weakness alone
  • Patient may demonstrate weakness.
  • Sustained activity of affected muscles increases weakness, which should improve after a brief test.
  • May be some mild atrophy of affected muscles in advanced cases
Respiratory
  • Patient may present in respiratory distress and with use of accessory muscles.
  • Have patient count from 1 to 25 with one breath. With sequential performance, a decline in ­respiratory function will be detected as the patient fails to count as high as on the prior attempt.
Other
  • Normal sensory exam
  • Reflex should remain unchanged; if present, a reduction in deep tendon reflex should be in ­proportion to the degree of muscle weakness.



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