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The purpose of this project was t o investigate the clinical forms of acquired myasthenia gravis in dogs. The medical records from 25 dogs with seropositive acquired myasthenia gravis were reviewed, and the following data were recorded for each patient: signalment, history, clinical findings; results of IV edrophonium chloride administration, repetitive nerve stimulation, and presence or absence of muscle membrane staining by immunocytochemical methods; serum acetylcholine receptor antibody concentration; treatment; and outcome. Several clinical forms of acquired myasthenia gravis were identified. Nine of the 25 patients (36%) had no historical or clinical evidence of appendicular muscle weakness, and were designated as focalmyasthenics. These dogs exhibited focal weakness in one or more of the following muscle groups: facial (3 of 9). pharyngeal (3 of 9). and laryngeal (3 of 9). The remaining 16 dogs (64%) exhibited appendicular muscle weakness. Four of these 16 dogs had acute onset and rapid development of clinical signs, and were designated as acute fulminating myasthenics. The remaining 12 dogs were classified as generalized myasthenics. All 4 dogs with acute fulminating myasthenia gravis had megaesophagus, 2 had facial muscle weakness, and 1 had pharyngeal muscle weakness. Ten of the 12 dogs with generalized myascquired myasthenia gravis (MG) is an immune-medi-A ated disorder in which autoantibodies against nicotinic acetylcholine (ACh) receptors of skeletal muscle are produced, resulting in impairment of action potential transmission from nerve to muscle.'-6 The mechanisms proposed for the antibody impairment of neuromuscular transmission include accelerated endocytosis of antibody cross-linked ACh receptors, complement-mediated destruction of postsynaptic muscle cell membrane in the vicinity of the ACh receptors, decreased synthesis and membrane incorporation of new ACh receptors, and direct interference of ACh receptor function by bound antib~dy.'.~ Myasthenia gravis is well documented in dogs, and exhibits many similarities to the corresponding disorder of people. 1~3,S,7,x The "classic" clinical presentation of a dog with acquired MG is episodic, generalized muscle weakness, most obvious in the appendicular muscles, that is worsened by activity and ameliorated with rest.'.i.' Megaesophagus is a common finding in dogs with acquired MG because of the large proportion of skeletal muscle in the esophagus of dogs.'," In people, several clinical forms of acquired MG have been described, which has prompted the development of a number of classification schemes.2.4.6. Io.i2-i7 M ost of the classification schemes describe a focal ocular form (involving extraocular muscles) and a generalized form characterized by appendicular muscle weakness,6.~n. I Z M . IS. 17.1 n The latter is subdivided into mild, moderate, and severe forms.'"~'Z.14.1'~'7 The subdivision of generalized MG in human beings is based upon the presence and degree of bulbar and respiratory muscle involvement, and the rate of progression of clinica...

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The histopathologic features in temporalis muscle biopsies from 29 dogs with masticatory muscle disorders were characterized and used for their subgrouping: 2 without lesions, 3 with nonspecific changes, 7 with neurogenic atrophy, and 16 with myositis. The immunocytochemical and immunochemical features of the muscle biopsies and sera from those dogs were compared among the histopathologic subgroupings and compared with biopsies and sera from healthy dogs and dogs with polymyositis. Of the 14 biopsies from dogs with masticatory muscle myositis, 12 had immune complexes limited to type 2M fibers, whereas 13 of 16 sera samples had detectable antibodies against type 2M fibers. The immune complex deposition was found only in biopsies of dogs with masticatory muscle myositis, and the antibodies were detected in the sera of only one dog that did not have masticatory muscle myositis. Immunoblot assays revealed that the antibodies were most often directed against a 185 K protein, myosin heavy chain, and a band that appeared to be LC2-M (myosin light chain 2-masticatory).

Serum from 35 cases of naturally occurring acquired canine myasthenia gravis (MG) were assayed for patterns of autoantibody specificities against canine acetylcholine receptor (AChR) using monoclonal antibodies (mAbs) and antiserum against defined regions of the AChR as competitive inhibitors of autoantibody binding. In human MG patients and in animals immunized with AChR purified from fish electric organs or mammalian muscle, most of the antibodies are directed against the main immunogenic region (MIR), a conformationally dependent region located on the extracellular surface of the alpha subunit away from the ACh binding site. In our studies using canine MG serum, we found that, as in human MG and in animals immunized with AChR, the antibody response is heterogeneous and predominantly IgG, with a large proportion of the autoantibodies directed against the MIR. The mAbs to the MIR blocked an average of 68% of serum antibody binding. A mAb to the beta subunit and polyclonal antiserum to the gamma subunit blocked an average of 34% and 39% of serum antibody binding, respectively, indicating that these subunits also contain relevant antigenic determinants, a pattern that has also been observed in human MG serum. Anti-alpha bungarotoxin binding site antibodies made up only a small fraction of the autoantibody population in canine MG as in human MG. These and other features described here suggest that canine MG is a useful model of human MG.