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Myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease in which IgG antibodies attack the acetylcholine receptors at the neuromuscular junction (see figures below). Acetycholine is the chemical responsible for communication between nerves. In MG, the body develops antibodies against the sites where acetylcholine binds, thus blocking their action. This results in skeletal muscle weakness. There are several forms of myasthenia gravis: generalized, focal, and acute fulminating. In the generalized form, the skeletal muscles of the limbs, especially the hind limbs, are affected and the patient has a gait that steadily worsens with exercise, and improves with rest.

In the focal form, only isolated skeletal muscle groups, usually oesophageal muscles, are affected. Acute fulminating myasthenia gravis is the most severe form. Generalized, profound skeletal muscle weakness progresses rapidly over a 24-48 hour period, to the point that the patient is typically recumbent and has generalized lower motor neuron deficits to the limbs and cranial nerves.

Contents

  • 1 Congenital MG
  • 2 Acquired MG
  • 3 Epidemiology
  • 4 Clinical features
  • 5 Course
  • 6 Diagnosis
    • 6.1 Edrophonium chloride (Tensilon) response test
    • 6.2 Neostigmine methylsulfate (Prostigmine) response test
    • 6.3 Electrophysiological testing
    • 6.4 Immunocytochemical testing
    • 6.5 Radiographs
    • 6.6 Laboratory
  • 7 Treatment

 

Congenital MG

In this condition, the patient is born without normal neuromuscular junctions to striated muscles. There is no effective treatment. Myasthenia gravis has been described as a recessive genetic disease in the Jack Russell terrier, the Springer Spaniel, and the Smooth Fox Terrier. The miniature dachshund gets a congenital form which actually resolves with age.

 

Acquired MG

This is a so-called “Autoimmune disease,” meaning that the immune system is destroying neuromuscular junctions as if they were foreign invaders. What muscles are affected depend on which junctions have been destroyed. Therapy centres on stopping this immune reaction and prolonging what acetylcholine activity is still present. This is done with a combination of immunosuppressive agents and medications to inhibit acetylcholinesterase. MG in cats is usually an acquired disease.

 

Epidemiology

Relative risk: higher after 2 to 3 years of age Breeds predisposition: Abyssinians (and related Somalis)

 

Clinical features

The two most common clinical manifestations of MG observed in cats were generalised weakness without megaoesophagus and generalised weakness associated with a cranial mediastinal mass. The incidence of megaoesophagus in MG cats is lower than what is seen in dogs, due primarily to the difference in distribution of skeletal muscles; cats having less skeletal muscles than dogs in this region.

Episodic weakness, including ventroflexion of the neck, lack of palpebral reflexes and less commonly regurgitation, change in vocalisation and cranial mediastinal masses have been described. A predisposition to acquired feline MG has been suggested for Abyssinians and r3elated Somali cats, because 6 of the 9 reported cases involved these breeds.

A significant number of MG cats also have underlying [hyperthyroidism].

 

Course

Cats: More frequent chronic course. Acquired drug-induced MG should be considered in hyperthyroid cats >10y.o that become weak after initiating treatment with methimazole.

 

Diagnosis

Diagnosis of acquired myasthenia gravis in dogs and cats is based on clinical history, neurologic exam findings, response to provocative tensilon testing, measurement of acetylcholine receptor antibody levels in blood, and repetitive nerve stimulation testing. Confirmation of myasthenia gravis is the same in cats and dogs. Myasthenia gravis is said to be a clinically obvious disease which does not normally require laboratory tests, however, there are many laboratory tests that can be done to confirm myasthenia gravis.

 

Edrophonium chloride (Tensilon) response test

One test that can be done is a endrophonium chloride (Tensilon) response test. Endrophonium chloride is a short acting anticholinesterase. This is not effective in cats, however, because they do not react predictably to the short acting anticholinesterase endrophonium chloride. Animals that are not already collapsed are made to do some type of exercise until weakness develops. After the exercise, the animal is given an injection of the anticholinesterase endrophonium chloride. Muscle strength following the injection of endrophonium chloride is evaluated. If there is no response after the first injection, a second can be given 1 – 2 minutes later, but the total dose should range from 0.5 – 5.0 mg IV depending on body weight. With a positive test, muscle strength improves within 10 – 30 sec after injection and decreases within 5 minutes. If no benefit is seen after 2 minutes, the test is negative. This test is not specific only for myasthenia gravis and other tests should be performed to confirm the disease.

 

Neostigmine methylsulfate (Prostigmine) response test

Other tests can be done in the same fashion as the edrophonium chloride response test using longer acting anticholinesterase drugs such as neostigmine methylsulfate. The dose is 0.05 mg/kg IM. Clinical improvements occur 15 – 30 minutes after the injection. A prior administration of atropine is required.

 

Electrophysiological testing

An electrophysiological test is done by repetitive supramaximal electrical stimulation to peripheral nerves at 3 – 5 stimuli per second. The decreasing response (action potentials) of the animal to the stimuli is observed. Normal animals will show a decreased response if greater than 20 stimuli per second is present. If there is a 10% decrease in response, it is suggestive that the animal has myasthenia gravis. If there is a 20% decrease, it is very reliable that the diagnosis is myasthenia gravis. If the decrease in response ceases after tensilon is injected, the diagnosis of myasthenia gravis is confirmed even more.

 

Immunocytochemical testing

Immunocytochemical testing can provide evidence of acquired myasthenia gravis. All that is needed for this test is a sample of the serum from the animal suspected to have myasthenia gravis. The serum of the animal is incubated with sections of normal muscle tissue. Antibodies from the patient’s serum that bind to the end-plates within the muscle are detected by enzyme- or fluorescence-linked secondary reagents. This shows the amount of antibodies that are aimed against the proteins on the end-plate of the muscle. However, this test is not specific only for the proteins on the acetylcholine receptors.

 

Radiographs

All cases of myasthenia gravis should have chest radiographs due to the great incident of megaesophagus and resulting apiration pneumonia. Also, the radiograph should be checked for the presence of cranial mediastinal masses due to the association of thymoma with myasthenia gravis.

 

Laboratory

Serum levels of antibodies against acetylcholine receptor (AChR) has been the most reliable diagnostic assay for the diagnosis of MG in humans and other animals. Determination of AChR antibodies is by immunoprecipitation radioimmunoassay; this is the gold standard for diagnosis of MG in cats. False positive rates are low but false negative rates do occur. The test is objective and quantitative and proves an autoimmune response against AChR, which differs from other causes of muscle weakness.

Serum AChR antibody titres

Negative <0.3 nmol/L
Positive > 0.55 – 12.0 nmol/L

 

Treatment

For cats with megaoesophagus: Small feedings while erect: Elevate food & water. Also consider gastrostomy If thymoma is evident, a thymectomy is recommended. For episodic or concurrent weakness, Physostigmine bromide (Syrup) is the drug of choice. Start with low dose as it may be poorly tolerated.

  • Physostigmine in cats: 0.5 mg/kg q 12 h po
  • Prednisone: Cats: 1.5 to 2 mg/kg q12h po

 

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