Myasthenia gravis

Myasthenia gravis causes muscular weakness that typically gets worse with exercise and improves with rest.^45,46 Congenital myasthenia gravis occurs rarely in dogs and is typically caused by a deficiency of acetylcholine receptors on the postsynaptic membrane. Clinical signs of weakness become apparent at 6 to 8 weeks of age, and diagnosis requires special studies to evaluate acetylcholine receptors in muscle biopsy samples of the intercostal muscles.^45,46 A spontaneously resolving form of congenital myasthenia gravis has been reported in a litter of dachshunds.⁴⁷

Acquired myasthenia gravis is a much more common disorder in which autoantibodies are directed against postsynaptic nicotinic acetylcholine receptors of skeletal muscle, resulting in impaired neuromuscular transmission. Golden retrievers and Labrador retrievers are commonly affected, probably reflecting the popularity of these breeds.^45,46 There seems to be a bimodal age distribution, with peaks of incidence at 2 to 3 and 9 to 10 years of age.^45,46

Dogs with appendicular weakness due to myasthenia gravis will usually be profoundly exercise intolerant, developing weakness and collapse after only a few steps. Myasthenia gravis is not a reasonable differential diagnosis in a dog with subtle decreases in exercise tolerance or in dogs with collapse that only occurs after 10 minutes of intense activity. Myasthenia gravis is typically definitively diagnosed by demonstrating serum antibodies directed against acetylcholine receptors (Comparative Neuromuscular Laboratory, School of Medicine, University of California San Diego: http://vetneuromuscular.ucsd.edu/).^45,46 Response to the ultra-short-acting anticholinesterase drug edrophonium chloride (0.1 to 0.2 mg/kg intravenously in dogs) may help to establish a clinical diagnosis of myasthenia gravis while the results of confirmative antibody testing are pending. Serum antibodies to nicotinic acetylcholine receptors are detected in 98% of dogs with generalized weakness due to myasthenia gravis, but even a single dose of prednisone can result in a negative test result.⁴⁶ Electrodiagnostic testing may be necessary in seronegative patients for which myasthenia gravis is still being strongly considered based on the history and clinical findings.^45,46 Dogs with myasthenia gravis will have a decrement in the amplitude of muscle action potentials generated in response to repetitive nerve stimulation.

Treatment with anticholinesterase medications (e.g. pyridostigmine bromide 1-3 mg/kg orally every eight to 12 hours) and upright feedings are recommended.^45,46 In patients without aspiration pneumonia, immunosuppression with low-dose prednisone and azathioprine can be recommended.⁴⁵ The mortality rate from aspiration pneumonia in dogs with myasthenia gravis approaches 50%. When managed successfully, regardless of the treatment used, more than 80% of dogs experience a clinical and immunologic remission within one year of diagnosis, with an average of 6.4 months.⁴⁸