Analysis of risk factors for acquired myasthenia in dogs.
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Age Factors↗
Biomedical subjects
G D Shelton
Publications and source records attributed to G D Shelton.
Adult-onset motor neuron disease in three cats.
Motor neuron diseases of domestic animals have rarely been described. Three cats with adult-onset, chronic, progressive generalized muscle weakness characterized initially by trembling on exertion and later by extreme difficulty in walking, cervical ventroflexion, dysphagia, and marked muscle atrophy were elevated. Spinal reflexes were evident early but were nondetectable as the disease progressed. Electromyography revealed fibrillation potentials, with nerve conduction velocities within the reference range. Histologic examination of muscle specimens revealed denervation. Marked neuron loss and gliosis were detected in the ventral horns of the spinal cord, with atrophy of ventral nerve rootlets. Less dramatic neuron loss was seen in brain stem motor nuclei. Electron microscopic examination of the ventral horns disclosed hypertrophied astrocytes, with densely arrayed intermediate filaments, swollen axons with large filamentous accumulations, and many macrophages with lipofuscin-like inclusions. Clinical and pathologic findings were consistent with a progressive neurodegenerative disease affecting spinal and some bulbar motor nuclei.
Age of Onset↗
Analysis of organic acids, amino acids, and carnitine in dogs with lipid storage myopathy.
Abnormal accumulations of lipid droplets, localized predominantly in histochemical type 1 fibers, were observed in fresh frozen sections of muscle biopsies from 25 dogs with myalgia, weakness, and muscle atrophy. Compared to controls, lactic acidemia, hyperalaninemia, lactic and pyruvic aciduria, variably increased urinary excretion of carnitine esters, and muscle carnitine deficiency were present. These findings support a metabolic block in oxidative metabolism resulting in lactic acidemia in dogs with lipid storage myopathy.
Acids↗
Myelin splitting, Schwann cell injury and demyelination in feline diabetic neuropathy.
Nerve biopsy samples from two cats with spontaneously occurring diabetes were examined. The predominant nerve fiber abnormalities observed were restricted to the myelin sheath and Schwann cell. Reactive, degenerative and proliferative Schwann cell changes were evident but the most striking abnormality encountered was splitting and ballooning of the myelin sheath. These observations highlight the significance of Schwann cell injury in the pathogenesis of diabetic neuropathy.
Animals↗
Risk factors for acquired myasthenia gravis in dogs: 1,154 cases (1991-1995).
OBJECTIVE: To determine frequency of initial clinical signs and risk factors for acquired myasthenia gravis (MG) in dogs. DESIGN: Retrospective study. SAMPLE POPULATION: 1,154 dogs residing within the United States from 1991 to 1995 with a confirmed diagnosis of acquired MG and 7,176 dogs with other neuromuscular disorders, including generalized weakness, megaesophagus, and dysphagia (control group). PROCEDURE: Records were retrieved from a database containing results of serum samples tested for acetylcholine receptor antibodies. Signalment, breed, age, state of origin, and month of onset of clinical signs were obtained. An antibody titer > 0.6 nmol/L was diagnostic for acquired MG. Unconditional logistic regression was used for statistical analysis. RESULTS: In comparison with mixed-breed dogs, dogs with the highest risk of acquired MG were Akitas, terrier group, Scottish Terriers, German Shorthaired Pointers, and Chihuahuas. Rottweilers, Doberman Pinschers, Dalmatians, and Jack Russell Terriers had low relative risks. Sexually intact males and dogs less than 1 year old had some protection from risk. Generalized weakness with megaesophagus and megaesophagus alone were the most common initial clinical signs. CLINICAL IMPLICATIONS: Breed predispositions for acquired MG were demonstrated. Age and sex were contributing factors. Although most dogs had generalized clinical signs, a substantial proportion of dogs had focal signs.
Aging↗
Methylmalonic and malonic aciduria in a dog with progressive encephalomyelopathy.
A 12 week old female Labrador retriever dog with signs of progressive diffuse degeneration of the brain and spinal cord was found to have methylmalonic and malonic aciduria. Over a 5 month period, the dog developed neurologic signs compatible with disease of the central nervous system with predominant diffuse cerebral and right lateralizing brainstem deficits. Gross pathological examination of the brain showed that the lateral, third, and fourth ventricles of the brain were markedly enlarged and associated with white and grey matter atrophy. Syringomyelia and hydromyelia of the central canal into the dorsal funiculus of the spinal cord beginning at the level of the cervical intumescence and extending to the lumbar intumescence was also present. Significant biochemical abnormalities include methylmalonic and malonic aciduria, mild lactic and pyruvic aciduria. There was also accumulation of citric acid cycle intermediates including succinic, aconitic, and fumaric acids. Disordered fatty acid oxidation was suggested by increased excretion of adipic, ethylmalonic, suberic and sebacic acids. Neither ketoacidosis nor hyperammonemia were present, and serum cobalamin levels were normal. Overall, this dog demonstrates an inborn error of metabolism resulting in abnormal organic acid accumulation associated with a neurodegenerative disease.
Animals↗
Megaoesophagus secondary to acquired myasthenia gravis.
Fifteen dogs with confirmed adult onset idiopathic megaoesophagus, in which no generalised muscle weakness was observed, were tested for the presence of acetylcholine receptor antibodies. Of these, six were found to have values greater than 0.6 nmol/litre, previously determined to be diagnostic of acquired myasthenia gravis. The mean serum titre value for these dogs was 5.59 nmol/litre (range 0.78 to 8.72 nmol/litre). It appears that a significant proportion of dogs presenting with megaoesophagus have myasthenia gravis and, if a prompt diagnosis and appropriate treatment can be instituted, clinical signs may improve.
Animals↗
Third degree atrioventricular block and acquired myasthenia gravis in four dogs.
Third degree atrioventricular block was diagnosed in 4 dogs with acquired myasthenia gravis (serum acetylcholine receptor antibody titer > 0.6 nmol/L). All 4 dogs had megaesophagus. Two dogs also had mediastinal thymomas, which were resected. One dog with thymoma received a permanent pacemaker at the same time that it underwent thymectomy; the other did not develop third degree atrioventricular block until 3 months after thymectomy. Both dogs with thymoma died of severe aspiration pneumonitis within 3 months after surgery. The third dog received a permanent pacemaker and was treated with pyridostigmine bromide, but also died of aspiration pneumonitis 1 month after the pacemaker was implanted. The fourth dog was treated with prednisolone and pyridostigmine bromide and improved, but did not become clinically normal. Because third degree atrioventricular block as well as myasthenia gravis can cause signs of weakness, acquired myasthenia gravis should be considered in dogs with idiopathic cardiac conduction disturbances. Likewise, an ECG should be evaluated in dogs with acquired myasthenia gravis.
Animals↗
D-2-hydroxyglutaric aciduria.
Hydroxyglutaric aciduria is detected by gas chromatographic-mass spectrometric analysis, and the D and L forms are quantified by chemical ionization with deuterated internal standards. Patients have recently been described who accumulate the D form, and they appear to be quite different from those with the more common L form. Experience is reported with three patients and an animal model with D-2-hydroxyglutaric aciduria. The phenotype appears to include mental retardation, macrocephaly, hypotonia, seizures, and involuntary movements, although neurologic and systemic manifestations of the disorder varied considerably between individual patients, even within the same family.
Animals↗
Multifocal myositis associated with Sarcocystis sp in a horse.
Multifocal myositis was diagnosed in a 7-year-old Quarter Horse gelding on the basis of history and findings on physical examination, serum biochemical analysis, electromyography, and microscopic examination of frozen sections of muscle biopsy specimens. Histologic examination of the muscle specimen revealed multifocal accumulations of histiocytes, lymphocytes, and plasma cells, with attendant myofiber degeneration and necrosis. Parasitic cysts with morphologic characteristics of Sarcocystis sp were found in regions of myocyte degeneration and necrosis, and in regions of normal muscle. Based on a tentative diagnosis of Sarcocystis sp-induced myositis, the horse was treated with trimethoprim/sulfamethoxazole and pyrimethamine for 28 days, phenylbutazone for 5 days, and paddock rest for 30 days. At the end of treatment, the horse had gained 35 kg, its appetite had returned to normal, and muscle mass was returning to normal. Sarcocystis fayeri is the only Sarcocystis sp reported in equine muscle in the United States and is rarely associated with acute myositis or muscle atrophy. The development of clinical signs in this horse could have been the result of an underlying immunosuppression or infection with a particularly pathogenic strain or large infective dose of S fayeri.
Animals↗
Antibodies to nicotinic acetylcholine receptors in dogs with megaoesophagus.
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Animals↗
Epitope mapping of monoclonal antibodies to Torpedo acetylcholine receptor gamma subunits, which specifically recognize the epsilon subunit of mammalian muscle acetylcholine receptor.
Epitopes for four monoclonal antibodies (mAbs) to the gamma subunit of Torpedo nicotinic acetylcholine receptor (AChR), and one mAb crossreactive with the gamma and delta subunits of Torpedo AChR were mapped using overlapping synthetic peptides corresponding to the complete amino acid sequence of Torpedo gamma subunit. The epitopes for all mAbs were within a 50 residue sequence region, on the cytoplasmic surface of the AChR. Three mAbs crossreacted with mammalian muscle AChRs. Two of them specifically recognized the epsilon subunit of AChRs at adult neuromuscular junction. The epsilon-specific mAbs were used, in conjunction with mAbs specific for the alpha and beta subunits and anti-peptide antisera specific for the epsilon, gamma and delta subunits, to identify in Western blots the subunit complement of embryonic and adult bovine muscle AChRs.
Amino Acid Sequence↗
Osteogenic sarcoma and myasthenia gravis in a dog.
A 7-year-old Saint Bernard developed muscular weakness 1 year after right forelimb amputation and adjuvant cisplatin chemotherapy for osteogenic sarcoma. Clinical and laboratory findings supported a diagnosis of myasthenia gravis, and the dog had clinical improvement in response to prednisone treatment. Two additional dogs with myasthenia gravis and osteogenic sarcoma were identified by review of the medical records of the University of California Veterinary Medical Teaching Hospital. Findings indicated that myasthenia gravis or other neuromuscular transmission disorders may be associated with muscular weakness in dogs with osteogenic sarcoma.
Animals↗
Mitogen stimulation of canine normal and myasthenia gravis lymphocytes.
Responses of canine lymphoid tissues to mitogens were studied in five normal dogs and in two dogs with acquired myasthenia gravis (MG). In the normal dogs, lymph-node-derived lymphocytes gave the most consistent proliferative responses to concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM), as determined by thymidine incorporation; and in most cases PHA, lipopolysaccharide (LPS), and PWM stimulated total IgG production, as determined by ELISA. Splenic lymphocytes had the greatest capacity for increased total IgG production. In the myasthenic dogs total IgG production by unstimulated lymph-node-derived lymphocytes was 88 micrograms/ml and 153 micrograms/ml, much higher than that of unstimulated normal dog lymphocytes (mean less than 1.0 microgram/ml). All mitogens resulted in suppression rather than stimulation of IgG production by lymphocytes from dogs with MG. Production of antibodies to acetylcholine receptors (AChRs) was detected in the supernatants of lymphocyte cultures from one of the dogs with MG at a rate of 78 fmol/5 x 10(5) cells per week and was not detected in culture supernatants of control dogs. This study demonstrates that lymph nodes may be an important site of antibody production in myasthenic dogs and provides the necessary groundwork for future studies of the cellular immunology of canine MG.
Animals↗
Disorders of neuromuscular transmission.
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Animals↗
Expression of fiber type specific proteins during ontogeny of canine temporalis muscle.
The canine masticatory muscles contain a unique adult fiber type composition and different contractile protein isoforms than do adult limb muscles. To determine when these characteristic proteins are expressed during development, samples from canine temporalis (masticatory) and pectineus (limb) muscles were compared between 55 days gestation and 60 days postpartum by histochemical, biochemical, and immunocytochemical analysis. At 55 days gestation and 3 days postpartum, both muscles contained identical histochemical type 2C fibers, native myosin isozymes, and myosin light and heavy chains. By 14 days postpartum, fiber-type expression in these muscles diverged, with resultant formation of type 1 and type 2M fibers in the temporalis muscle and type 1 and 2A fibers in the pectineus muscle. The distinctive myosin isoforms, light chains, and heavy chain of the temporalis muscle were also expressed 2 weeks postpartum. Based on the methods used in this study, we conclude that (1) the temporalis muscle develops from embryonic fibers that initially contain a myosin indistinguishable from embryonic limb muscle fibers, suggesting they have a common precursor, and (2) the myosin light chains and heavy chain unique to the temporalis muscle are initially expressed 2 weeks postpartum.
Animals↗
Canine and human myasthenia gravis autoantibodies recognize similar regions on the acetylcholine receptor.
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.
Animals↗
Canine masticatory muscle disorders: a study of 29 cases.
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).
Animals↗