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.     

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.     

Clinical Forms of Acquired Myasthenia Gravis in Dogs: 25 Cases (1988–1995)

The purpose of this project was to 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 acetyl-choline 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 focal myasthenics. These dogs exhibited focal weakness in one or more of the following muscle groups: facial {3 of 9), pharyngeal (3 of 9), and laryn-geal (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 myasthenia gravis had megaesophagus, 4 had facial muscle weakness, 4 had pharyngeal muscle weakness, and 3 had laryngeal muscle weakness. Historical or clinical evidence of exercise-associated appendicular weakness was found in only 6 of the 12 (50%) dogs with generalized myasthenia gravis, and in none of the dogs with acute fulminating myasthenia gravis. Seven of the 12 dogs with generalized myasthenia gravis had weakness primarily (n = 1) or exclusively (n = 6) of the pelvic limbs. Two of the 4 dogs with acute fulminating myasthenia gravis had primarily pelvic limb weakness. Twelve of the 25 dogs (48%) died or were euthanized shortly after admission to the hospital due to aspiration pneumonia. The dogs with acute fulminating myasthenia gravis had a markedly higher 1-year mortality rate in comparison with the other 2 groups. The use of immunosuppressive therapy had a significant positive effect on patient survival, regardless of the type of myasthenia gravis. This investigation demonstrates that acquired myasthenia gravis in dogs is a disorder with a wide spectrum of clinical forms, similar to the analagous disorder in people.     

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.     

Use of radiographic measurements in distinguishing myasthenia gravis from other causes of canine megaoesophagus

OBJECTIVES: To evaluate whether dogs with megaoesophagus due to myasthenia gravis display less oesophageal dilatation radiographically than dogs with other causes of megaoesophagus. METHODS: Thoracic radiographs of 66 dogs with megaoesophagus in which concurrent acetylcholine receptor antibody titre was known were analysed retrospectively. Maximum oesophageal diameter was transformed to a "relative oesophageal diameter" using a ratio with thoracic inlet diameter. Dogs were divided into two groups according to "MG" or "non-MG" antibody status and median relative oesophageal diameter values were compared between groups and with age, weight and sex. A receiver operating characteristic plot was used to evaluate a suitable relative oesophageal diameter cut-off. RESULTS: Twenty dogs were diagnosed with myasthenia gravis and 46 with other causes of megaoesophagus. Thoracic inlet size correlated significantly with bodyweight and surface area (r(2)=0.627 and 0.669, respectively). Median values of relative oesophageal diameter for the MG group and non-MG group were 0.58 and 0.66, respectively, and these showed a small, but significant, difference (P=0.029), although there was complete overlap in the range of relative oesophageal diameter values between groups. There was no significant association between relative oesophageal diameter and sex, age or weight or significant difference in age, sex or weight between the two groups. An increased odds ratio for myasthenia gravis existed in golden retrievers and German shepherd dogs. CLINICAL SIGNIFICANCE: Relative oesophageal diameter appears to be of limited diagnostic utility in distinguishing dogs with megaoesophagus due to myasthenia gravis from those with megaoesophagus due to other causes.     

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.     

Megaoesophagus and glucocorticoid-deficient hypoadrenocorticism in a dog

A seven-year-old German shepherd dog was referred for acute onset regurgitation. Muscle weakness and severe dermatological disease were present. Thoracic radiographs revealed generalised megaoesophagus. Diagnostic testing revealed glucocorticoid deficiency, and rapid resolution of the megaoesophagus followed appropriate supplementation. The dog made a full recovery. Unique features of this case include a transiently positive antinuclear antibody titre and clinical features of myasthenia gravis.     

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.     

Autoimmune form of myasthenia gravis in a juvenile Yorkshire Terrier x Jack Russell Terrier hybrid contrasted with congenital (non-autoimmune) myasthenia gravis of the Jack Russell

A case of juvenile onset myasthenia gravis is described in a Yorkshire Terrier x Jack Russell bitch in which there were serum autoantibodies to acetylcholine receptors and reduction in the muscle's content of acetylcholine receptors. Approximately 25% of the receptors remaining were complexed with antibody. After 8 months of treatment with the anticholinesterase pyridostigmin, the animal made a complete recovery and the serum level of antibody decreased. The condition of this dog in many respects resembled acquired myasthenia gravis of adult onset and is contrasted with the seven cases of congenital myasthenia gravis which we have studied in the Jack Russell Terrier. In the congenital form of myasthenia gravis, reduction of acetylcholine receptors in muscle is found without any demonstrable autoantibodies to acetylcholine receptors, either in serum or muscle.     

Congenital and acquired neuromuscular disease of young dogs and cats

Neuromuscular disorders in small animals include a diverse group of congenital and acquired diseases. The prognosis will vary according to the disorder and the portion of the motor unit affected. A number of diseases might be satisfactorily treated (for example, myasthenia gravis, congenital myotonia), whereas others may be self-limiting (for example, hereditary myopathy of Labrador Retrievers). Accurate diagnosis is necessary for establishing a prognosis and treatment plan suitable to the patient and client. Specific diagnosis in the absence of specialized tests is difficult, although not always impossible (for example, congenital myotonia in the Chow Chow). A knowledge of the neuromuscular diseases that might affect small animals, a detailed history, and a thorough physical examination will help in the presumptive diagnosis. Specialized laboratory examinations may need to be applied (for example, antiacetylcholine receptor antibody titer for acquired myasthenia gravis). Referral may be necessary for more detailed diagnostic workup (for example, electromyographic examination, nerve or muscle biopsy examination). In the case of inherited neuromuscular disorders, a knowledge of inheritance patterns will allow genetic counseling to avoid future problem breedings.     

Acquired myasthenia gravis in a cat with thymoma

A 4-year-old castrated Abyssinian cat was evaluated for profound neuromuscular weakness. Results of electromyography and repetitive nerve stimulation tests were normal. Thoracic radiography revealed a cranial mediastinal mass, which was excised and identified as a thymoma. Serum acetylcholine receptor antibodies were detected at high concentration, supporting a diagnosis of acquired myasthenia gravis. Clinical signs of disease responded to treatment with pyridostigmine and corticosteroids.     

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.     

Treatment of acquired myasthenia gravis associated with thymoma in two dogs

Two cases of myasthenia gravis associated with thymoma are reported. Both were female German shepherd dogs and the thymoma was surgically resected. Aspiration pneumonia secondary to persistent megaoesophagus was a complication in both cases. The myasthenia gravis did not resolve, but there was a more satisfactory control of clinical signs with anticholinesterase treatment. Corticosteroid therapy was used in one case, but the resulting polydipsia increased the incidence of regurgitation, resulting in recurrent episodes of aspiration pneumonia.     

Acquired myasthenia gravis: what we have learned from experimental and spontaneous animal models.

Acquired myasthenia gravis (MG) is a disorder of neuromuscular transmission in which muscle weakness results from an autoantibody mediated depletion of acetylcholine receptors (AChR) at the neuromuscular junction. Experimental autoimmune myasthenia gravis, described in rodents and rabbits, has provided a good model of the effects of the autoimmune response against AChR and has shown that the specificities of the immune response in MG are those that would be obtained by immunization with native AChR. It has provided little information, however, about what initiates and sustains the immune response in MG. Acquired MG occurs spontaneously in dogs and may be the most common neuromuscular disorder that can be diagnosed in this species. As in human MG, an autoimmune response against AChR has been demonstrated and AChR autoantibodies have been implicated in the pathogenesis. The variability in clinical presentation, methods of diagnosis, and occurrence with other autoimmune diseases and neoplasia are identical to that of humans. Future studies of spontaneous canine autoimmune MG may provide clues to the determination of what factors initiate and sustain the autoimmune response to AChR, and in the study of specific suppression of the autoimmune response against AChR.     

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.     

Myasthenia gravis in two cats

A case of the autoimmune form of myasthenia gravis and a case of what is probably a congenital form of myasthenia gravis were diagnosed in 2 unrelated cats. Neuromuscular weakness exacerbated by exercise was a prominent feature in both cats. Weakness was eliminated temporarily by administration of anticholinesterase drugs. Serum autoantibodies to acetylcholine receptors of skeletal muscle were present in the 1st cat and were not detected in the 2nd cat. A characteristic decrement in the amplitude of the compound muscle action potential during repetitive stimulation of the motor nerve was elicited in the 2nd cat. There was marked electromyographic improvement in response to anticholinesterase drugs. Electromyography was not performed in the 1st cat.     

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.     

Myasthenia Gravis in the Cat

Myasthenia gravis (MG) was diagnosed in four cats--one had an apparently congenital form and three had the acquired autoimmune form. All four cats were examined because of episodes of weakness including gait abnormalities, voice change, neck ventroflexion, and regurgitation. Palpebral reflexes were absent in all cats. Administration of edrophonium chloride resulted in transient resolution of clinical signs in all four cats. Three cats were tested for the presence of serum autoantibodies against acetylcholine receptor (AChR) by radioimmunoassay. Two cats with acquired MG had anti-AChR antibody titers of 10.5 and 96.8 nmol/l (normal, less than or equal to 0.03 nmol/l). Antibodies were not detected in the cat with presumptive congenital MG. All four cats were treated with pyridostigmine bromide. Two cats with acquired MG were euthanatized because of clinical deterioration. The third cat with acquired MG has been asymptomatic since 2 months after diagnosis. The cat with presumed congenital MG is alive 3 years after diagnosis.     

Oesophageal compliance in naturally occurring canine megaoesophagus

SUMMARY The passive blomechanical property of oesophageal compliance (OC) was measured in 8 naturally occurring cases of canine megaoesophagus, 8 matched control and 7 vagotomised control dogs. Of the 8 dogs with megaoesophagus, 6 had congenital Idiopathic megaoesophagus and 2 had secondary megaoesophagus attributable to generalised skeletal muscle disease. Stepwise distension of the whole oesophagus was employed for measurement of OC at the 4.0 and 8.0 mL/kg Injected volume steps within the control volume range (0 to 12.0 mL/kg). At both Injected volume steps OC was higher In megaoesophagus dogs than in either matched control or vagotomised control dogs (P / 0.01 In both cases), and no significant difference was observed In OC between matched control and vagotomised control dogs. No correlation was demonstrated between OC and the estimated duration of clinical signs of dogs with megaoesophagus. These findings suggest that In most cases of canine megaoesophagus the viscoelastic properties of the oesophageal wall are significantly altered, that In such cases the disorder is unlikely to be purely dynamic and that processes other than the duration of oesophageal dilatation are responsible for the alteration in oesophageal wall blomechanical properties. The relevance of these findings to current concepts on pathophysiological mechanisms underlying the evolution and resolution of various forms of canine megaoesophagus Is 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.