History
A 5-year-old neutered male German Shepherd Dog was presented for evaluation of chronic, progressive, intermittent vomiting and regurgitation, hypersalivation, inappetence, and weight loss. The patient had been adopted 2 years previously, and initial signs of intermittent regurgitation and vomiting were noted within a few months after adoption. A multitude of medical therapies were prescribed by the primary veterinarian, including sucralfate, famotidine, omeprazole, metoclopramide, probiotics, novel protein diets, and amoxicillin. No improvement was noted with past medical treatment. In the 6 months preceding presentation, the patient’s clinical signs had markedly progressed, and the patient had lost a total of 9 kg of body weight. On physical examination, the patient displayed marked ptyalism, lip licking, frequent hard swallowing, and occasional retching with production of clear fluid. Tachycardia was noted, and lung sounds were normal to decreased ventrally on auscultation, with intermittent referred upper airway noise. The patient had generalized muscle atrophy and was mildly weak. No neurologic deficits were found. Three-view thoracic radiographic images were obtained (Figure 1).
Thoracic left lateral (A), right lateral (B), and ventrodorsal (C) radiographic images of a 5-year-old neutered male German Shephard Dog that was presented for evaluation of chronic, progressive, intermittent vomiting and regurgitation, hypersalivation, inappetence, and weight loss.
Citation: Journal of the American Veterinary Medical Association 261, 9; 10.2460/javma.23.03.0140
Radiographic Findings and Interpretation
Thoracic radiography revealed a ventrally distributed, patchy interstitial to alveolar pattern in the right cranial, right middle, and left cranial lung lobes (Figure 2). The entirety of the intrathoracic esophagus was visible and mildly dilated, containing both gas and soft tissue/fluid opacity. The caudal aspect of the intrathoracic esophagus was focally widened with a round, opaque soft tissue structure that varied in appearance between the lateral projections. There were multiple pockets of gas in the cranial mediastinum highlighting the outer margins of the trachea and margins of the cranial mediastinal vasculature, consistent with pneumomediastinum. The contour of the diaphragm was irregular, characterized by flattening and concavity in some regions with undulant margins. Based on the clinical history and imaging findings, the pulmonary changes were consistent with bronchopneumonia, presumed to be secondary to aspiration. Differential diagnoses for pneumomediastinum in this patient included esophageal perforation, severe coughing resulting in the Macklin effect, or iatrogenic injury from jugular venipuncture. The diffuse esophageal dilation was consistent with megaesophagus. Differential diagnoses for the focal dilation of the caudal intrathoracic esophagus and intraluminal soft tissue structure included a mass, hiatal hernia, or, less likely, foreign body. A videofluoroscopic swallowing study had initially been planned to further investigate the patient’s dysphagia. This was canceled following survey radiography, however, given the possibility of esophageal perforation resulting in pneumomediastinum and the presence of aspiration pneumonia.
Same images as in Figure 1. There is a ventral alveolar pattern (black arrowheads). There is a rounded soft tissue opacity with internal gas in the region of the caudal intrathoracic esophagus (black arrows) that differs in appearance in A and B. The esophagus cranial to this level is diffusely mildly distended with fluid and gas. The diaphragm is flattened with an undulant contour (white arrowheads). Pneumomediastinum is present (white arrows).
Citation: Journal of the American Veterinary Medical Association 261, 9; 10.2460/javma.23.03.0140
Treatment and Outcome
The patient was started on maropitant, pantoprazole, fentanyl, and IV fluids while being monitored in the hospital. Nasal cannulas were placed to provide oxygen supplementation due to the development of a low oxygen saturation. A few hours later, high-flow oxygen supplementation was initiated due to a persistently low oxygen saturation and increased respiratory effort despite treatment. Given the patient’s respiratory compromise and poor prognosis, the owners elected euthanasia for the dog, followed by necropsy. At necropsy, multiple appendicular muscles had regions of streaking pallor consistent with myopathy. The diaphragm muscle was markedly hypertrophied up to 1 cm thick with multiple areas of pallor and fibrosis. Similar muscular degeneration was observed in all areas of the myocardium, and a portion of the right atrioventricular valve leaflet was dysplastic and tightly adhered to the endocardium. The thoracic portion of the esophagus was severely distended with gas, and the mucosa was eroded, indicating megaesophagus with reflux esophagitis. There was no evidence of esophageal perforation, and an easily reduced hiatal hernia was present. The cause of the patient’s pneumomediastinum was not definitively identified and could have been from an airway rupture from struggling to breathe. The right cranial and middle lung lobes had areas of aspiration pneumonia with edema noted in all lung lobes and the bronchi. Samples of skeletal muscle and all major organs were collected, suspended in neutral-buffered 10% formalin, and routinely processed for paraffin embedding. Sections (5-μm slice thickness) of each tissue were stained with H&E stain. In all skeletal muscles examined, the myofibers were disorganized with marked variation in size and orientation. Degenerate myocytes displayed loss of cross striations and vacuolation of the sarcoplasm. Scattered myocytes had sarcoplasm fragmentation suggestive of necrosis. In the diaphragm, myocytes were frequently multinucleated with rowing of nuclei (Figure 3), proliferation of satellite cells, and fibrosis of the endo-, epi-, and perimysium, consistent with attempted myofiber regeneration. Esophageal muscular degeneration and aspiration pneumonia were also confirmed histologically. These findings were consistent with an unspecified muscular dystrophy, with the marked diaphragmatic hypertrophy suggestive of X-linked Duchenne-type muscular dystrophy.
Photomicrograph of a section of diaphragm muscle from the same dog. The skeletal muscle myofibers display marked variation in size and orientation. There is internalization and rowing of nuclei (white arrowhead), consistent with attempted myofiber regeneration. Scattered myofibers are necrotic (black arrow). H&E stain; bar = 30 µm (400X magnification).
Citation: Journal of the American Veterinary Medical Association 261, 9; 10.2460/javma.23.03.0140
Comments
Muscular dystrophies in humans are a group of inherited progressive, degenerative myopathies.1 This disorder is due to mutations in the dystrophin gene encoding for cytoskeletal protein resulting in skeletal muscle atrophy and weakness.1 Histologically, there is a spectrum of changes where there is muscle fiber degeneration and necrosis leading to an influx of inflammatory cells followed by muscle fibers being replaced with fibrous and fatty tissue.1 Duchenne muscular dystrophy is the most severe and common X-linked disorder, affecting human males at a rate of anywhere from 1 in 3,500 to 5,000.1,2 Deaths in humans tend to occur in the second to third decade of life as the result of respiratory or cardiac failure.1 Duchenne-type muscular dystrophy has been reported in mice, cats, and dogs, with the canine model of X-linked muscular dystrophy having a similar presentation and clinical course as humans. Thoracic radiographic changes have been reported in Golden and Labrador Retrievers with X-linked muscular dystrophy.3,4 The most common radiographic finding of Golden and Labrador Retriever muscular dystrophy is flattening and a scalloped contour of the diaphragm due to muscular hypertrophy, as was seen in this case.3,4 Megaesophagus, aspiration pneumonia, and gastroesophageal hiatal hernia are also frequent radiographic findings, as were also present in this dog.3,4
The final diagnosis of Duchenne-type muscular dystrophy can be achieved by obtaining muscle biopsies for histological evaluation.2 Phenotypic variation can be seen among affected patients, leading to varying histological changes of degeneration, regeneration, and fibrosis.2,5 In the current case, muscle biopsies were obtained during the necropsy from the following tissues: the diaphragm, tongue, esophagus, intercostal muscle, cardiac muscle, and skeletal muscle from both the hind and forelimb. The skeletal muscle groups exhibited multifocal areas of moderate to severe degeneration, regeneration, and fibrosis of the myofibers. Histopathologic interpretation of the myocardium revealed changes consistent with severe cardiomyocyte loss and fibrofatty replacement. The gastrointestinal smooth muscle was unaffected.
Muscular dystrophy has been previously reported in Golden Retrievers, Labrador Retrievers, Rottweilers, German Shorthaired Pointers, Pembroke Welsh Corgis, Cocker Spaniels, Beagles, Tibetan Terriers, Cavalier King Charles Spaniels, and Brittany Spaniels.1,2,5 To our knowledge, there are no reported cases of muscular dystrophy in German Shepherd Dogs, and this is the first published report describing the radiographic, necropsy, and histological features of muscular dystrophy in a German Shepherd Dog. While rare, X-linked Duchenne-type muscular dystrophy should be considered as a differential diagnosis in patients with muscle weakness, chronic dysphagia, regurgitation, recurrent aspiration pneumonia, and radiographic changes including megaesophagus, hiatal hernia, and undulant diaphragmatic margins. Advanced imaging such as CT and MRI may be helpful to confirm diaphragmatic thickening and assess for concurrent musculoskeletal abnormalities. Muscle biopsy is ultimately required for a definitive diagnosis. Currently, there are no known standard treatment options for muscular dystrophy other than supportive care.
Acknowledgments
No external funding was used in this study. The authors have nothing to declare.
References
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