Veterinary Information: Myasthenia Gravis in Dogs and Cats

Terminology: Myasthenia gravis (MG) literally means grave (gravis) muscle (my-) weakness (asthenia). It is a common cause of generalised weakness in dogs and occasionally cats.

Etiology: Myasthenia Gravis is an acquired or congenital condition resulting in an inefficient neuromuscular signal transmission.

Congenital:
A reduced or imperfect synthesis of the acetylcholine receptors. More uncommon than the acquired form.

Acquired:
Most common form in dogs and cats. Auto-immune disease in which auto-antibodies (IgG) are formed against the acetycholine receptors on the postsynaptic membrane of the muscular cells. This results in an ineffecient neuromuscular transmission.
1.)The auto-antibodies bind to the acetylcholine receptors on the postsynaptic muscle membrane.
2.)This reduces the amount of available receptors for acetycholine to bind to.
3.)Normal signal transmission between peripheral nerve ending and myocyt is blocked.
4.)Result: muscle weakness

Predisposion:
Breeds:
Dogs: Labradors, Golden Retrievers, Terriers breeds, German Shepherds, Springer Spaniels. (also mentioned: Akitas, German pointers, Chihuahuas, Rottweilers, Doberman pinchers, Dalmatians, Jack Russels).
Cats: Asian Breeds (Abyssinians, Somalis)
Age: Dogs: mostly between 2-3 years of age or older than 9 years.
Gender: less common in intact male dogs (possibly due to testosterone influence).

Symptoms: Characteristic: worsening muscle weakness during exercise. Improving during rest. Clinical symptoms can vary widely from focal forms (approx. 36 %) with subclinical signs, to more generalized forms with more severe symptoms (25% acute and in 39% a more chronic development).

-dysphony (altered barking sound)
-mega-oesophagus (80-90% of the dogs with generalised form)
-mimical changes due to affected facial muscles
-tetraparesis (with normal correction reflexes!)
-dyspnea

Possible complications of a mega-oesophagus:
-concurrent regurgitation
-aspiration pneumonia

Diagnosis of acquired myasthenina gravis:
Clinically:
-Characteristic symptoms.
-Administration of a short-acting ACh-Esterase Inhibitor: edrophonium chloride. Administer 0.1-0.2 mg/kg Tensilon IV; several minutes later an improvement of the clinical symptoms can be seen.
-EMG: An electromyogram in a patient with MG will show a diminishing muscle response on repetitive stimulation.

Definitive Diagnosis of the acquired form:
Detecting serum auto-antibodies that react with á-bungarotoxin extracted acetylcholine receptors. This can be performed at the Comparative Neuromuscular Laboratory at the University of California. For more information on blood sample transmission and costs visit can be found on their website: http://vetneuromuscular.ucsd.edu/index.html. The serum test is specific for Myasthenia Gravis and has a sensitivity of approx. 15%.

Treatment: A long acting ACh-Esterase Inhibitor can be administered to treat a generalised muscle weakness due to MG. By inhibiting the enzyme ACh-Esterase, less of the ACh that is already bound to the Ach-R will be broken down, enhancing the duration of the ACh effect. There will also be more ACh in the synaps available to compete with the Auto-Ab for binding to the ACh-Receptors on the post-synaptic membranes.

Oral long-acting ACh-Esterase Inhibitor:
Pyridostigmine bromide 1-3 mg/kg Orally q 8-12 hours in dogs and cats. Start therapie at 1 mg/kg and increase the dosis up to 3 mg/kg on effect.

Intramuscular long-acting ACh-Esterase Inhibitor:
Neostigmine 0.04 mg/kg IM q 6 hours. This is a good alternative for animals that recurrently regurgitating and oral therapy is not a reasonable option.

Immune-suppressive drugs (corticosteroids) may be administered but can be controversial in patients with aspiration pneumonia. Immune-suppressive therapy has however also shown to shorten the duration of Myasthenia Gravis in other patients.

Treating pneumonia and preventing future aspiration pneumonia. Several drugs should be avoided in patient with MG as they can decrease the neuromuscular transmission and therefore enhance the symptoms of muscle weakness. (reported drugs that should be avoided are: aminoglycoside antibiotics, anti-arrhythmias, phenothiazines, methoxyflurane, magnesium) Advice for the owner: High feeding and drinking bowls and holding the upper body, neck and head in an elevated position for 5-10 minutes after feeding.

Contra-indicated drugs: Drugs with a diminishing effect on the neuromuscular junction. Reported drugs that should be avoided are: aminoglycoside antibiotics, anti-arrhythmias, phenothiazines, methoxyflurane, magnesium.

Prognosis: ACh-Esterase Inhibitors have a minor effect on improving esophageal motility. Therefore the risk of aspiration pneumonia is still apparent in animals treated for MG. It is a main cause for lethality in patient suffering from MG, causing up to 50% of the Myasthenia Gravis patients to die within the first two weeks after diagnosing Myasthenia Gravis.

The prognosis is good for patients with a well controlled Myasthenia Gravis. Spontaneous remission can occur after months or years. A possible reoccurrence of Myasthenia Gravis in these cases has also been reported.

Prognosis is also dependant on the underlying cause of a generalised immune dysfunction. Possible causes are: Paraneoplastic syndrome (diverse neoplasias, frequently thymomas). A occurrence in combination with other immune-mediated endocrinopathies has also been reported in higher frequency (hypoadrenocortsicism, hypothyroidism, myocarditis).

Congenital Myasthenia Gravis: Autosomal recessive in Jack Russels, smooth-haired Fox Terriers and English Springer Spaniels. It is also reported in Siamese and Domestic short-haired cats. No remissions from the congenital form are reported. Congenital Myasthenia Gravis is a chronically progressive condition that usually results in paralysis despite treatment with ACh-Esterase Inhibitors.

Literature:
Ettinger SJ, Feldman EC, Textbook of Veterinary Internal Medicine, WB Saunders Company, Philadelphia (2000) 5th edition: 675-676


Veterinary Topics and Pet Health
Return from Myasthenia Gravis to the Veterinary Info Database