Myasthenia Gravis

THIS NEUROMUSCULAR DISEASE CAN BE CONGENITAL OR ACQUIRED.

By Jeff Grognet, D.V.M., B.Sc.(Agr.)
Dogs in Canada May 2009 issue

The term “myasthenia gravis” was coined for a frequently fatal disease in people. Even just three decades ago, up to 25 per cent with this disease died. Older veterinary textbooks concurred and gave dogs with myasthenia gravis a poor prognosis for recovery. However, we now know that early recognition of the disease and appropriate treatment can often give a fairly normal lifespan, at least with the acquired form.

Characterized by extreme muscle weakness, myasthenia gravis (MG) is a disorder of the neuromuscular junction. There is poor transmission of the impulse from the nerve to the awaiting muscle and the muscle fails to contract properly. This can be either acquired (it develops with age) or congenital (the dog is born with it).

To understand how MG occurs, we have to take a short course in neurology. Electrical impulses travel down nerves from the spinal cord to muscles. There is a space between the nerve and the muscle that the impulse has to ‘jump’. This space is called a synapse.

The transmission of the electrical impulse across the synapse is accomplished by a neurotransmitter – a hormone released from the sending side (presynaptic membrane) that activates receptors on the receiving side (postsynaptic membrane). This allows the impulse to carry on into the muscle and trigger a contraction.

Impulse transmission can be interrupted in several ways. Damaging the nerve stops the electrical impulse from traveling, so it never reaches the synapse. This can occur if a nerve is cur or if the spinal cord is damaged (e.g., a herniated disk). In these cases, there is paralysis of a small group of muscles; one or two legs may not work.

There can also be failure of the impulse to cross the synapse. When this occurs, we have MG.

CONGENITAL MG
Congenital MG can occur as a presynaptic or postsynaptic problem. In Jack Russell Terriers and Springer Spaniels, a postsynaptic disorder can occur as early as six to nine weeks of age. In this case, it is inherited as an autosomal recessive trait. Only pups that have acquired a faulty gene from each parent show the disease.

The neurotransmitter hormone that diffuses across the synapse is acetylcholine (ACh). These breeds lack ACh receptors on the postsynaptic side. This deficiency of receptors reduces the sensitivity of the membrane to ACh. Affected dogs have generalized weakness and fatigability that is exacerbated by exercise. Additional signs are lameness, collapse, drooling and tremors.

The problem with congenital MG is that the condition is progressive; periods of weakness become longer and more exaggerated, ultimately leading to generalized weakness, muscle wasting and an inability to walk.

Congenital MG in Smooth Fox Terriers is often accompanied by megaesophagus. In this ailment, there is a lack of muscular strength in the wall of the esophagus that leads from the throat to the stomach. The esophagus distends with food, which is then regurgitated in the same form it went down. It isn’t digested because it fails to reach the stomach. The real problem with megaesophagus is that the food can be aspirated (inhaled) to the lungs as it is regurgitated, triggering an often-fatal pneumonia.

This type of MG is diagnosed by a Tensilon test – an injection of edrophonium chloride, a cholinesterase inhibitor that blocks the enzymes that break down ACh. This prolongs the effects of ACh so it can stimulate the existing receptors.

The Tensilon test can cause a dramatic amelioration of the signs, making a dog that is recumbent and flat out able to return to normal activity. This lasts for only a few minutes before muscle weakness gradually returns.

Dogs with this type of MG can be treated with the enzyme blocker Mestinon once daily. Unfortunately, the response is erratic – there are frequent relapses and dogs often become refractor to treatment. Because of this, the prognosis for congenital MG is guarded.

Another congenital (postsynaptic) disorder has been identified in Miniature Dachshund puppies at five to six weeks of age. The difference is that it responds to therapy and also resolves as the puppy matures. The inheritance has not been determined.

A presynaptic congenital MG has also been reported in 12 – to 16-week-old Gammel Dansk Honsehund dogs, again with an autosomal recessive inheritance. They either do not produce enough ACh, or the neurotransmitter they do manufacture does not work properly.

They have exercise-induced weakness but no advanced signs and no megaesophagus. There is no treatment for this form of MG, but it is not progressive.

ACQUIRED MG
The type of MG that strikes dogs most commonly is the acquired form. This is an immune-mediated disease where the immune system is out of control, manufacturing antibodies that attach to the ACh receptors. These antibodies can be detected with a blood test.

Acquired MG is sometimes associated with disease in the thymus gland. One theory is that the dog produces antibodies against cancerous cells in the thymus that cross-react with the ACh receptors.

MG has also been reported in dogs with other types of cancer, including bone osteosarcomas and anal sac adenocarcinomas. This is called paraneoplastic MG. However, most acquired MG does not have an identifiable cause.

MG should be suspected if you see a progressive lack of muscle strength during exercise, that comes on over a period of days or weeks. In some dogs, the first sign is megaesophagus. In fact, in some cases of MG, only the esophagus is involved and there is no generalized weakness. This is focal MG.

To diagnose acquired MG, veterinarians can use the Tensilon test. There is also a blood test for ACh receptor antibodies that detects almost all cases of acquired MG (it misses about two per cent of afflicted dogs). If in doubt, the dog can be put on medication to see if there is a positive response. These tests should be done sooner rather than later because megaesophagus is potentially fatal.

Medical treatments of acquired MG usually entails giving cholinesterase inhibitors. There needs to be a trial and error approach to drugs as well as their frequency and dose. Some dogs may become well controlled only to become refractory to treatment after a period of time. In these cases, steroids may be tried along with other immunosuppressive drugs. Success of treatment depends on whether or not there is a tumour of any sort. If there is one, MG can be difficult to treat, and the tumour itself can create its own symptoms.

If megaesophagus is a concern, elevating the food bowl or feeding the dog on stairs can assist in propelling food down to the stomach. If pneumonia is suspected, it should be treated aggressively with antibiotics and other medications.

There is also an acute fulminating form of MG that has a propensity for rapid development of megaesophagus and secondary aspiration pneumonia. These dogs can become debilitated so quickly that they can’t even breathe. Ventilatory support is necessary, as well as intravenous fluids and lots of nursing care.

There is a little good news. Some dogs appear to go into remission after a period of being successfully controlled. This means MG can be a treatable disease.

Because there is a genetic predisposition in both the acquired and congenital forms, dogs with myasthenia gravis should not be bred. Vaccinations (and stimulation of the immune system) during active MG should be avoided. Whether or not vaccinations can trigger MG is an unresolved question.

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A multi-published writer, Jeff Grognet, D.V.M., B.Sc.(Agr.), runs a veterinary practice in Qualicum Beach, B.C., along with his wife, fellow veterinarian Louise Janes, D.V.M.