Definition

A disorder of neuromuscular transmission characterized by muscular weakness and excessive fatigability.

Pathophysiology

Transmission failure at the neuromuscular junction-results from structural or functional abnormalities of the nicotinic AChRs or other end-plate proteins and enzymes (congenital form) and from autoantibody-mediated destruction of AChRs and postsynaptic membranes (acquired form).

Systems Affected

• Neuromuscular-result of abnormalities or destruction of AChRs, choline acetyltransferase or end-plate cholinesterase.
• Respiratory-may find aspiration pneumonia secondary to megaesophagus.

Genetics

• Congenital familial forms-Jack Russell terrier, springer spaniel, smooth fox terrier; smooth-haired miniature dachshund, Gammel Dansk Hønsehund, Labrador retriever; autosomal recessive mode of inheritance.
• Acquired-as with other autoimmune diseases, requires appropriate genetic background for disease to occur; multifactorial, involving environmental, infectious, and hormonal influences.
• Familial forms of acquired MG occur in the Newfoundland and Great Dane breeds.

Incidence/Prevalence

• Congenital-rare
• Acquired-not uncommon in dogs; uncommon in cats

Geographic Distribution

Worldwide

Signalment

Signs

Causes

• Congenital
• Immune-mediated
• Paraneoplastic

Risk Factors

• Appropriate genetic background
• Neoplasia-particularly thymoma
• Methimazole treatment (cats)-may result in reversible disease
• Vaccination can exacerbate active MG
• Intact female

Differential Diagnosis

• Other disorders of neuromuscular transmission-tick paralysis; botulism; cholinesterase toxicity.
• Acute or chronic polyneuropathies.
• Polymyopathies-including polymyositis.
• Diagnosis depends upon a careful history, thorough physical and neurologic examinations, and specialized laboratory testing.

CBC/Biochemistry/Urinalysis

• Normal.
• Serum creatine kinase activity-usually normal; may be elevated if MG is associated with polymyositis and concurrent thymoma.

Other Laboratory Tests

• Serum AChR antibody titer-diagnostic for acquired form.
• Thyroid and adrenal function-may see abnormalities associated with acquired form.

Imaging

Thoracic radiographs-megaesophagus; cranial mediastinal mass, aspiration pneumonia.

Diagnostic Procedures

• Ultrasound-guided biopsy of cranial mediastinal mass-may support diagnosis of thymoma.
• Dramatic increase in muscle strength after administration of edrophonium chloride (0.1 mg/kg IV)-may see false-negative and false-positive responses.
• Decreased or absent palpebral reflex-may return after edrophonium chloride administration.
• Electrophysiologic evaluation-necessity questionable with increased availability of AChR antibody testing; many patients with acquired form are poor anesthetic risks.
• Electrocardiogram-with bradycardia; third-degree heart block has been documented in some patients with acquired disease.

Pathologic Findings

Biopsy of a cranial mediastinal mass may reveal thymoma, thymic hyperplasia, or thymic atrophy.

Appropriate Health Care

• Inpatient-until adequate dosages of anticholinesterase drugs are achieved.
• Aspiration pneumonia-may require intensive care
• Gastrostomy tube-may be required if patient is unable to eat or drink without significant regurgitation.

Nursing Care

• Oxygen therapy, intensive antibiotic therapy, intravenous fluid therapy, and supportive care-generally required for aspiration pneumonia.
• Nutritional maintenance with a gastrostomy tube-multiple feedings of a high-caloric diet; good hygiene care.
• Elevation of food and water.

Activity

Self-limited owing to the severity of muscle weakness and extent of aspiration pneumonia.

Diet

May try different consistencies of food-gruel; hard food; soft food; evaluate what is best tolerated.

Client Education

• Warn client that, although the acquired disease is treatable, most patients require months of special feeding and medication.
• Inform client that a dedicated owner is important to a favorable outcome for acquired myasthenia.
• Prognosis is poor for congenital myasthenic syndrome.

Surgical Considerations

• Cranial mediastinal mass-thymoma.
• Before attempting surgical removal, stabilize patient with anticholinesterase drugs and treat aspiration pneumonia.
• Weakness may not be clinically evident initially.
• Suspected thymoma-test all patients for acquired MG before surgery.

Drug(s) Of Choice

• Anticholinesterase drugs-prolong the action of acetylcholine at the neuromuscular junction; pyridostigmine bromide tablets or syrup (Mestinon syrup, diluted half and half in water) at 1–3 mg/kg PO q8–12h.
• Corticosteroids 0.5 mg/kg q24h; initiated if there is a poor response to pyridostigmine or if there is no response to the edrophonium chloride challenge.

Contraindications

Avoid drugs that may reduce the safety margin of neuromuscular transmission-aminoglycoside antibiotics; antiarrhythmic agents; phenothiazines; anesthetics; narcotics; muscle relaxants; magnesium.

Precautions

• Avoid large volumes of barium for evaluating megaesophagus.
• Large air-filled esophagus seen on survey radiographs-barium study not indicated.
• Avoid immunosuppressive dosages of prednisone-may worsen muscle weakness.
• Avoid unnecessary vaccinations.

Possible Interactions

N/A

Alternative Drug(s)

• Azathioprine 2 mg/kg PO through gastrostomy tube q24h. Taper to q48h when clinical remission of the disease.
• Mycophenolate 20 mg/kg PO q12h. Reduce dosage by 50% once significant improvement or resolution of clinical signs is noted.

Patient Monitoring

• Return of muscle strength should be evident.
• Thoracic radiographs-evaluated every 4–6 weeks for resolution of megaesophagus.
• AChR antibody titers-evaluated every 8–12 weeks; decrease to the normal range with immune remission.

Prevention/Avoidance

N/A

Possible Complications

• Aspiration pneumonia
• Respiratory arrest

Expected Course and Prognosis

• No severe aspiration pneumonia or pharyngeal weakness-good prognosis for complete recovery; resolution usually within 6–8 months.
• Thymoma present-guarded prognosis unless complete surgical removal and control of myasthenic signs are achieved.

Associated Conditions

• Other autoimmune disorders-thyroiditis; skin disorders; hypoadrenocorticism, thrombocytopenia, hemolytic anemia, inflammatory bowel disease.
• Disorders of the thymus-thymoma; thymic hyperplasia.
• Other neoplasias.

Age-Related Factors

Bimodal age of onset-1–4 years of age and 9–13 years of age.

Zoonotic Potential

N/A

Pregnancy/Fertility/Breeding

• Humans-weakness may improve during pregnancy but worsens after delivery; some neonates of affected mothers have a temporary myasthenia gravis-like weakness that lasts several days to weeks that is due to in utero transfer of autoantibodies from the mother.
• Documented in dogs after whelping.

See Also

• Chapters covering autoimmune diseases
• Megaesophagus

Abbreviations

• AChR = acetylcholine receptor
• MG = myasthenia gravis

Internet Resources

Comparative Neuromuscular Laboratory: http://vetneuromuscular.ucsd.edu.

Client Education Handout Available Online