Focal myasthenia gravis in a dog.

A 10-month-old American cocker spaniel was evaluated for megaesophagus, aspiration pneumonia, but no appendicular muscle weakness. During hospitalization, weakness of the facial muscles developed, this resolved with anticholinesterase administration. Serum antibodies against acetylcholine receptors were documented, confirming the diagnosis of focal myasthenia gravis. Diagnosis, management, and medical treatment are discussed.     

Treatment of a Myasthenic Dog with Mycophenolate Mofetil

A ten‐year‐old, male castrated Springer Spaniel was presented for dysphagia, ptyalism, and regurgitation. Evidence of megaesophagus and mild aspiration pneumonia were apparent on thoracic radiographs. A diagnosis of focal acquired myasthenia gravis was suspected and subsequently confirmed with a positive serum acetylcholine (ACh) receptor antibody concentration (3.87 nM/L). A gastrostomy tube was placed shortly after presentation; food and drugs (including azathioprine) were administered through the tube. After transient improvement, the dog suddenly deteriorated clinically, experiencing frequent episodes of regurgitation and developing severe aspiration pneumonia. Mycophenolate mofetil (MMF), a novel immunosuppressive drug with relative specificity for lymphocytes, was instituted every twelve hours via the gastrostomy tube. Within four days of beginning MMF therapy, both clinical evidence of pharyngeal/esophageal dysfunction and radiographic evidence of megaesophagus had resolved. Initially, clinical side‐effects of combined MMF/AZA administration were not apparent, but the patient experienced several vomiting episodes during the third week of treatment. The vomiting resolved after decreasing the dose of both drugs. The patient made a full recovery, and a one‐month follow‐up ACh receptor antibody concentration was normal (0.26 nM/L). After one month of combination therapy, the patient was weaned off of AZA and maintained on MMF as the sole immunosuppressive drug. The dog was subsequently weaned off of MMF on two occasions. Mycophenolate mofetil was reinstituted after the first discontinuation due to the development of profound appendicular muscle weakness two days after stopping MMF; the weakness resolved within 24 hours of reinstituting MMF. A positive ACh receptor antibody concentration (0.89 nM/L) after the second MMF weaning prompted the second reinstitution of MMF. Two months following this second MMF reinstitution, the dog was again serologically negative (0.51 nM/L) for myasthenia gravis. At the time of last followup, the dog remained in clinical remission eight months after initial presentation. The use of MMF to treat acquired myasthenia gravis in dogs has not been reported previously. The literature concerning MMF and its potential use in treating patients with autoimmune diseases is discussed.     

Acquired Myasthenia Gravis

Serum samples from 152 dogs with a clinical diagnosis of idiopathic megaesophagus without detectable generalized muscle weakness were tested for the presence of antibodies to acetylcholine receptors by immunoprecipitation radioimmunoassay. Positive serum antibody titers (mean, 3.1 nmoL/L; range, 0.77-30 nmoL/L; reference values less than 0.6 nmoL/L) were found in 40 dogs (26%), with German Shepherd dogs (8/25, 32%) and Golden Retrievers (7/20, 35%) having a greater percentage of positive submissions. By immunocytochemical methods, localization of immune complexes at the neuromuscular junction after incubation of serum with normal canine muscle was documented in an additional 17 cases (11% of all samples submitted) that did not have increased antibody titers to acetylcholine receptors. Of the 40 seropositive dogs, 17 (48%) had a clinical improvement or remission of clinical signs associated with decreasing AChR antibody titers. Idiopathic megaesophagus has been associated with a poor prognosis; however, this study demonstrates that a large percentage of the dogs have myasthenia gravis and that with supportive treatment, the clinical signs may improve or resolve.     

Use of mycophenolate mofetil as a rescue agent in the treatment of severe generalized myasthenia gravis in three dogs

Objective – To describe the use of IV and oral mycophenolate mofetil (MMF) as adjunctive therapy in 3 dogs with severe generalized myasthenia gravis.
Case Series Summary – Three dogs suffering from severe generalized myasthenia gravis as confirmed by acetylcholine antibody titers were treated with MMF as part of their treatment regimens. All 3 dogs had radiographic evidence of megaesophagus and suffered from severe regurgitation. Each dog was initially treated with pyridostigmine and supportive agents. When clinical remission was not achieved, IV MMF was administered to all dogs. Signs of clinical remission were apparent within 48 hours and all dogs were later maintained on oral MMF following resolution of regurgitation.
New or Unique Information Provided – This is the first report of the use of IV MMF as adjunctive treatment in dogs with severe generalized myasthenia gravis. Outcome was favorable in all 3 dogs and no adverse effects were noted from the MMF.     

Risk factors for acquired myasthenia gravis in cats: 105 cases (1986-1998)

OBJECTIVE: To determine prevalence of initial clinical signs and risk factors for acquired myasthenia gravis (MG) in cats. DESIGN: Retrospective case-control study. ANIMALS: 105 cats from the United States, Canada; and the United Kingdom with a confirmed diagnosis of acquired MG and 510 cats with other neuromuscular disorders, including generalized weakness, megaesophagus, and dysphagia (control group). PROCEDURES: Records were retrieved from a data-base containing results of serum samples tested for acetylcholine receptor antibodies. Signalment, including breed, age, and state or country of origin, month of onset, and initial clinical signs were obtained. An acetylcholine receptor antibody titer > 0.3 nmol/L was diagnostic for acquired MG. Unconditional logistic regression was used for statistical analysis. RESULTS: Compared with mixed-breed cats, the breed with the highest relative risk of acquired MG was the Abyssinian (including Somali). Significant differences between sexes were not detected. There was no compelling evidence for a difference in risk of developing MG between states or countries. Relative risk increased after 3 years of age. The most common clinical signs were generalized weakness without megaesophagus and weakness associated with a cranial mediastinal mass. Focal signs, including megaesophagus and dysphagia without signs of generalized weakness, were also evident. CONCLUSIONS AND CLINICAL RELEVANCE: A breed predisposition for acquired MG in Abyssinians (and related Somalis) was observed. Clinical signs were variable and included generalized weakness, megaesophagus, and dysphagia. A cranial mediastinal mass was commonly associated with MG in cats.     

Congenital Myasthenic Syndrome in the Dog Breed Gammel Dansk Hønsehund: Clinical,Electrophysiological, Pharmacological and Immunological Comparison with Acquired Myasthenia gravis

The effect of anticholinesterase drugs on the clinical and electrophysiological features in a canine congenital myasthenic syndrome is compared with findings in acquired myasthenia gravis in dogs. Anticholinesterase treatment had no effect on muscle weakness or electrophysiological parameters in the congenital myasthenic syndrome in contrast to its effect on clinical signs and electrophysiological parameters in acquired myasthenia gravis. The lack of effect of anticholinesterase in congenital myasthenia suggests a presynaptic defect as the aetiological factor. No antibodies to acetylcholine receptors were found in the Danish dog breed Gammel Dansk Hønsehund with the myasthenic syndrome. This classifies the disease in the group of canine and human congenital myasthenic diseases.     

Adult onset acquired myasthenia gravis in three Great Dane littermates

Acquired canine myasthenia gravis is an autoimmune disease in which autoantibodies are directed against muscle postsynaptic nicotinic acetylcholine receptors. Three adult great dane littermates were evaluated over a four month time period for an acute onset of generalised neuromuscular signs. All three dogs had elevated serum acetylcholine receptor antibody titres, which were considered diagnostic for acquired myasthenia gravis. Identification of three littermates with acquired myasthenia gravis in a breed with a low relative risk of developing the disease suggests a familial and possibly a genetic predisposition to myasthenia gravis in this family of dogs.     

Diseases of the horse: the centennial of a great book

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.     

Mega-oesophagus 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.     

Electromyographic and esophagomanometric findings in clinically normal dogs and in dogs with idiopathic megaesophagus.

Electromyography of 12 clinically normal dogs and 7 dogs with idiopathic megaesophagus revealed trains of positive sharp waves in the muscles of facial expression and in the lingual muscles of both groups. Positive waves are usually indicative of motor-unit disease; however, they are clinically insignificant in these muscles. Positive sharp waves were detected in the esophageal muscle of one dog with congenital megaesophagus. Esophageal electromyograms obtained in a dog with congenital megaesophagus and in 2 clinically normal dogs were normal. Resting caudal esophageal sphincter pressure was similar in both clinically normal dogs (mean, 22.3 mm of Hg; range, 15--37 mm of Hg) and in dogs with congenital or acquired idiopathic megaesophagus (mean, 29.6 mm of Hg; range, 20--50 mm of Hg).     

Canine myasthenia gravis

Decreased acetylcholine receptor content of the neuromuscular junction underlies the muscular weakness seen in both acquired and congenital myasthenia gravis. Immune mediated mechanisms account for the acquired defect while decreased membrane insertion of receptor leads to the congenital disorder. The congenital form typically presents in the first few weeks of life with generalised episodic weakness as the predominant sign. Although treatment with cholinesterase inhibitors may help temporarily, the prognosis is poor. Acquired myasthenia gravis can occur between eight months and 13 years of age and may present as megaoesophagus alone or as exercise-related weakness in conjunction with megaoesophagus. Although treatment of the immune mediated form is often successful and spontaneous remissions also occur, aspiration pneumonia secondary to megaoesophagus remains a major cause of mortality in affected dogs. Resolution of megaoesophagus must therefore be a major goal for future treatment regimes. The remarkable similarity between canine and human acquired myasthenia gravis suggests that the canine thymus gland warrants greater attention pathologically and perhaps therapeutically considering the value of thymectomy in human patients.     

Acquired myasthenia gravis in a poodle

An 11-year-old, spayed female, teacup poodle was evaluated for a chronic cough, lethargy, hindlimb weakness, and reluctance to exercise. Thoracic radiographs revealed megaesophagus and aspiration pneumonia. Serum antibodies against acetylcholine receptors confirmed the diagnosis of myasthenia gravis. The unusual clinical history and case outcome are discussed.     

Myasthenia gravis and disorders of neuromuscular transmission.

Myasthenia gravis is a disorder of neuromuscular transmission that occurs in congenital and acquired autoimmune forms. Acquired myasthenia gravis is probably the most common neuromuscular disorder in dogs that can be diagnosed and treated. An early, accurate diagnosis and appropriate therapy is of utmost importance to a good clinical outcome in this disorder. This article focuses on the diagnosis and treatment of acquired myasthenia gravis in dogs and cats with brief discussions of other disorders of neuromuscular transmission, including congenital myasthenia gravis, tick paralysis, botulism, and organophosphate intoxication.     

Classification of myasthenia gravis and congenital myasthenic syndromes in dogs and cats

Myasthenia, a syndrome of impaired neuromuscular transmission, occurs as either an acquired or congenital condition. Myasthenia gravis (MG) is an acquired autoimmune disorder with autoantibodies against the neuromuscular junction (NMJ) of skeletal muscle whereas congenital myasthenic syndromes (CMSs) are a clinically heterogeneous group of genetic disorders affecting the NMJ with a young age of onset. Both conditions are diseases for which recognition is important with regard to treatment and outcome. We review the published literature on MG and CMSs in dogs and cats, and by comparison with published classification used in humans, propose a classification system for MG and CMSs in dogs and cats. Myasthenia gravis is first classified based on focal, generalized, or acute fulminating presentation. It then is subclassified according to the autoimmune disease mechanism or seronegativity. Autoimmune disease mechanism relates to the presence or absence of a thymoma, or administration of thiourylene medication in cats. Congenital myasthenic syndromes are classified according to the affected NMJ component, the mechanism of the defect of neuromuscular transmission, the affected protein, and ultimately the mutated gene responsible. In proposing this categorization of MG and CMSs, we hope to aid recognition of the disease groups for both conditions, as well as guide treatment, refine prognosis, and provide a framework for additional studies of these conditions.     

Acquired immune-mediated myasthenia gravis in a cat associated with a cystic thymus

Acquired myasthenia gravis was diagnosed in a five-year-old domestic shorthair, neutered, female cat with generalised muscle weakness, tremors, dysphagia and alterations in voice. Radiographs indicated the presence of a mass in the anterior thorax. A response to edrophonium chloride, and raised levels of anti-acetylcholine receptor antibodies in the serum, confirmed the diagnosis and indicated an immune-mediated aetiology. Clinical remission occurred following thymectomy and the use of immunosuppressive corticosteroids. This is the first fully-documented case of acquired feline myasthenia gravis associated with the presence of a thymic abnormality in the United Kingdom. The clinical features, laboratory findings and response to treatment are compared with those reported previously in cats and other species.     

Clinical remission following plasmapheresis and corticosteroid treatment in a dog with acquired myasthenia gravis

A 7-year-old sexually intact male Labrador Retriever with regurgitation and generalized muscular weakness resulting from acquired myasthenia gravis received 2 plasmapheresis treatments in combination with corticosteroid treatment. Plasmapheresis was performed in an attempt to rapidly lower serum acetylcholine receptor binding antibody (AChR Ab) concentration. Seven days after the second plasmapheresis treatment, the dog's muscular strength was normal, which coincided with a 70% decrease in serum AChR Ab concentration. Because the dog also received corticosteroids, it is impossible to determine how much of the clinical improvement resulted from plasmapheresis.     

Canine trichinosis with signs of neuromuscular disease

A six-year-old fox terrier bitch, used for badger hunting, developed acutely progressive painless disturbance of locomotion with pronounced weakness. Evidence of central nervous disease or myasthenia gravis was not present. Muscle histology revealed trichinella larvae and changes consistent with a combined inflammatory myopathy and neuropathy. An enzyme-linked immunosorbent assay (ELISA) showed significantly increased serum levels of antibodies to Trichinella spiralis antigen. It is likely that the signs of neuromuscular disease shown by the dog were due to the trichinella infection. The case illustrates that symptomatic trichinosis should be considered in the clinical workup of myopathies in dogs with access to potentially trichinella-infected wildlife.     

Acquired idiopathic laryngeal paralysis as a prominent feature of generalised neuromuscular disease in 39 dogs

A retrospective evaluation of 17 dogs treated surgically for idiopathic acquired laryngeal paralysis demonstrated a marked variability in outcome, with many dogs continuing to exhibit weakness and exercise tolerance. In a subsequent prospective study, 22 consecutive affected dogs were tested for neurological deficits by neurological examination, electrodiagnostic evaluation, and blood analysis to measure thyroxine and thyroid-stimulating hormone and to detect any evidence of myasthenia gravis. Clinical neurological deficits and/or electrodiagnostic abnormalities were found in each case. There was limited evidence that specific neurological deficits were associated with a poor prognosis for full recovery of exercise tolerance. None of the dogs was positive for anti-acetylcholine receptor antibodies, and only three showed evidence of thyroid dysfunction.     

Canine inflammatory myopathies: a clinicopathologic review of 200 cases

A retrospective study was performed on 200 randomly selected cases of inflammatory myopathy in dogs from diagnostic muscle biopsies received at the Comparative Neuromuscular Laboratory, University of California, San Diego. The most common clinical signs in dogs diagnosed with an inflammatory myopathy were generalized weakness, stilted gait, dysphagia, masticatory or generalized muscle atrophy, inability to open the jaw, megaesophagus, and dysphonia. Myalgia was rarely described. Age of onset ranged from 0.25 to 14 years. Genders were equally represented. Breed distribution approximated the 2002 American Kennel Club registration statistics (r = .85) with the notable exception of Boxers and Newfoundlands. From the results of muscle biopsies, clinical signs, and presence or absence of antibodies against type 2M fibers, dogs were classified as a generalized inflammatory myopathy (gIM)--including immune-mediated polymyositis; infectious and preneoplastic myositis; and, rarely, dermatomyositislike or overlap syndromes or unclassified myositis-or a focal inflammatory myopathy (flM)--including masticatory muscle and extraocular myositis. Average creatine kinase (CK) and aspartate aminotransferase (AST) concentrations in gIMs were significantly higher than those with fIMs (P < .05). Neoplasia developed in 12 of 200 dogs within 12 months of diagnosis of polymyositis, with lymphoma diagnosed in 6 of 32 Boxers. Inflammatory myopathy was associated with antibody titers against infectious diseases in 38 dogs. Neospora caninum and Hepatozoon americanum cysts were found in tissues of 2 dogs not serologically tested. Antibodies against an unidentified sarcolemmal antigen were found in 9 of 19 Newfoundlands with polymyositis. The spectrum of canine inflammatory myopathies can be broad, with infectious etiologies relatively common, and can include preneoplastic and uncharacterized syndromes.     

Immune‐mediated myasthenia gravis in a methimazole‐treated cat

A 12‐year‐old female neutered ragdoll crossbred cat was presented for investigation of generalised weakness and regurgitation. The cat was being treated with transdermal methimazole for hyper‐thyroidism, which had been diagnosed 10 weeks previously. An acetylcholine receptor antibody titre was consistent with acquired myasthenia gravis. Withdrawal of methimazole and treatment with pyridostigmine was followed by resolution of clinical signs and reduction of the acetylcholine ‐receptor antibody titre. Medical control of hyperthyroidism was subsequently achieved with carbimazole, administered in conjunction with pyridostigmine, and no recurrence of clinical signs was observed. Myasthenia gravis is an uncommon but clinically significant adverse effect of methimazole therapy in cats, and may be caused by immunomodulatory properties of this drug. An adverse drug reaction should be considered in cats receiving methimazole that develop myasthenia gravis, and potentially also other immune‐mediated disorders.