eMedicine Specialties > Emergency Medicine > Neurology

Myasthenia Gravis

Author: William D Goldenberg, MD, Clinical Assistant Instructor, Department of Emergency Medicine, Kings County Hospital Center and SUNY Downstate Medical Center
Coauthor(s): Richard H Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Jan 30, 2009

Introduction

Background

Myasthenia gravis (MG) is a relatively rare autoimmune disorder of peripheral nerves in which antibodies form against acetylcholine (ACh) nicotinic postsynaptic receptors at the myoneural junction. A reduction in the number of ACh receptors results in a characteristic pattern of progressively reduced muscle strength with repeated use of the muscle and recovery of muscle strength following a period of rest.

The bulbar muscles are affected most commonly and most severely, but most patients also develop some degree of fluctuating generalized weakness.¹ The most important aspect of myasthenia gravis for emergency physicians is the detection and management of the myasthenic crisis.

Pathophysiology

Autoantibodies (immunoglobulin G [IgG]) develop against ACh nicotinic postsynaptic receptors for unknown reasons, although certain genotypes are more susceptible.

Cholinergic nerve conduction to striated muscle is impaired by a mechanical blockage of the binding site by antibodies and, ultimately, by destruction of the postsynaptic receptor.

Patients become symptomatic once the number of ACh receptors is reduced to approximately 30% of normal. The cholinergic receptors of smooth and cardiac muscle have a different antigenicity than skeletal muscle and are not affected by the disease.

The role of the thymus in the pathogenesis of myasthenia gravis is not entirely clear, but 75% of patients with myasthenia gravis have some degree of thymus abnormality (eg, hyperplasia in 85% of cases, thymoma in 15% of cases). Given the immunologic function of the thymus and the improvement in the clinical condition of patients following thymectomy, the thymus is suspected to be the site of autoantibody formation. However, the stimulus that initiates the autoimmune process has not been identified

Frequency

United States

The prevalence of myasthenia gravis in the United States ranges from 0.5-14.2 cases per 100,000 people. The prevalence has increased over the past 2 decades, primarily because of the increased life span of patients with the disease but also because of earlier diagnosis.²

Mortality/Morbidity

• In the past (pre-1960), untreated myasthenia gravis carried a mortality rate of 30-70%. In the modern era, patients with myasthenia gravis have a near-normal life expectancy.
• Morbidity results from intermittent impairment of muscle strength, which may cause aspiration, increased incidence of pneumonia, falls, and even respiratory failure if not treated.³  In addition, the medications used to control the disease may produce adverse effects.
• With prompt diagnosis and treatment, the mortality rate of myasthenic crisis is less than 5%.

Race

Onset of myasthenia gravis at a young age is slightly more common in Asians than in other races.²

Sex

• The male-to-female ratio of myasthenia gravis in children and adults is 2:3.
• A female predominance exists in the young adult peak (ie, patients aged 20-30 y), and a slight male predominance exists in the older adult peak (ie, patients older than 50 y).^1,2
• The male-to-female ratio in children with myasthenia gravis and another autoimmune condition is 1:5.

Age

Onset of myasthenia gravis peaks in neonates because of transfer of maternal autoantibodies, in those aged 20-30 years, and in those older than 50 years.

Clinical

History

Most patients who present to the ED have an established diagnosis of myasthenia gravis (MG) and are already taking appropriate medications. The activity of the disease fluctuates, and adjustments in medication dosages must be made accordingly. Noncompliance with medications, infection, and other physiologic stressors may result in a fulminant exacerbation of the disease.

• Many other factors influence cholinergic transmission, including drugs, temperature, and emotional state. 
• The adverse effects of many medications may provoke exacerbations; therefore, carefully obtaining a medication history is important. Some of the medications reported to cause exacerbations of myasthenia gravis include the following:
  • Antibiotics - Macrolides, fluoroquinolones, aminoglycosides, tetracycline, and chloroquine
  • Antidysrhythmic agents - Beta-blockers, calcium channel blockers, quinidine, lidocaine, procainamide, and trimethaphan
  • Miscellaneous - Diphenylhydantoin, lithium, chlorpromazine, muscle relaxants, levothyroxine, adrenocorticotropic hormone (ACTH), and, paradoxically, corticosteroids²
• Thyroid disorders may be seen in as many as 10% of patients with myasthenia gravis, and symptoms of hyperthyroidism or hypothyroidism may be present.  
• Rarely does a patient present with undiagnosed myasthenia gravis. However, if this situation does occur, typical complaints are of generalized weakness and reduced exercise tolerance that improves with rest. Patients with myasthenia gravis do not present with primary complaints of sleepiness or muscle pain. The patient may also complain of a specific weakness of certain muscle groups (eg, those used when climbing stairs).  
• The distribution of muscle weakness follows a characteristic pattern; initially 85% of patients have involvement of the eyelids and extraocular muscles resulting in ptosis and/or diplopia.¹ The involvement of the facial muscles results in changes in expression and speech, whereas involvement of the pharyngeal muscles results in progressive difficulty with mastication and deglutition.  
• In 15-20% of patients, myasthenia gravis affects the bulbar muscles alone. The other patients progress to generalized myasthenia gravis.¹  
• Neck and proximal limb weakness may occur.  
• Respiratory weakness may be present. Respiratory failure occurs in 1% of patients.  
• Eighty-five percent of patients with bulbar weakness go on to develop generalized weakness involving the limbs.

Physical

Patients with myasthenia gravis can present with a wide range of signs and symptoms, depending on the severity of the disease.

• Mild presentations of myasthenia gravis may be associated with only subtle findings, such as ptosis, that are limited to bulbar muscles. Findings may not be apparent unless muscle weakness is provoked by repetitive or sustained use of the muscles involved.  
• Recovery of strength is seen after a period of rest or with application of ice to the affected muscle. Conversely, increased ambient or core temperature may worsen muscle weakness.  
• Severe exacerbations of myasthenia gravis may present dramatically. 
  •  Facial muscles may be slack, and the face may be expressionless.
  • The patient may be unable to support his or her head, which will fall onto the chest while the patient is seated.
  • Jaw is slack.
  • Voice has a nasal quality.
  • Body is limp.
  • Gag reflex is often absent, and such patients are at risk for aspiration of oral secretions.⁴
• Respiratory distress
  • The patient's ability to generate adequate ventilation and to clear bronchial secretions are of utmost concern with severe exacerbations of myasthenia gravis.
  • Inability to cough leads to an accumulation of secretions; therefore, rales, rhonchi, and wheezes may be auscultated locally or diffusely. The patient may have evidence of pneumonia (ie, fever, cough, dyspnea, consolidation).
• Cholinergic crisis
  • One of the confusing factors in treating patients with myasthenia gravis is that insufficient medication (ie, myasthenic crisis) and excessive medication (ie, cholinergic crisis) can present in similar ways.
  • Cholinergic crisis results from an excess of cholinesterase inhibitors (ie, neostigmine, pyridostigmine, physostigmine) and resembles organophosphate poisoning. In this case, excessive ACh stimulation of striated muscle at nicotinic junctions produces flaccid muscle paralysis that is clinically indistinguishable from weakness due to MG.
  • Myasthenic crisis or cholinergic crisis may cause bronchospasm with wheezing, bronchorrhea, respiratory failure, diaphoresis, and cyanosis.⁴
  • Miosis and the SLUDGE syndrome (ie, salivation, lacrimation, urinary incontinence, diarrhea, GI upset and hypermotility, emesis) also may mark cholinergic crisis. However, these findings are not inevitably present.
  • Despite muscle weakness, deep tendon reflexes are preserved.

Causes

• The cause of myasthenia gravis is unknown, but it is clearly an autoimmune disease in which the specific antibody completely has been characterized. In up to 90% of generalized cases, IgG to the nicotinic Ach receptor is present.³
• Females and people with certain human leukocyte antigen (HLA) types have a genetic predisposition to autoimmune diseases. 
• As with other autoimmune diseases, a derangement of immune regulation occurs.
• Sensitization to a foreign antigen that has cross-reactivity with the nicotinic ACh receptor has been proposed as a cause of myasthenia gravis, but the triggering antigen has not yet been identified.

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