Comparative Neuromuscular Laboratory

Genetic analysis of dogs with acquired myasthenia gravis

This prospective study is a collaborative effort between the UC Davis Genetics Laboratory, the UC Davis Neurology/Neurosurgery Service, and the Comparative Neuromuscular Laboratory (CNL) at the University of California San Diego. After confirmation of a diagnosis of acquired myasthenia gravis (MG) by demonstration of a positive acetylcholine receptor (AChR) antibody titer (UCSD), genetic analysis will be performed at the UC Davis Genetics Laboratory to determine the haplotype of the Major Histocompatibility Complex (MHC) of dogs with MG.  Determination of a (screenable) genetic predisposition would facilitate both greater understanding of MG in dogs, and identify dogs at risk for developing MG.  Dogs that are clinically affected with MG, or dogs currently in remission may be enrolled in this study.

Acquired MG is a disorder of neuromuscular transmission, caused by autoimmune destruction of the nicotinic acetylcholine receptor (AChR) in skeletal muscle, resulting in AChR depletion. Depletion of AChRs results in inadequate depolarization of the muscle with subsequent muscle weakness.(Go to July 2008 Case of the Month.)Acquired MG is a relatively common disease in dogs, and although many dogs go into spontaneous remission, MG can have a devastating effect if not recognized early and treated appropriately. MG is the most commonly recognized immune-mediated neurological disease in dogs and cats. Most dogs with MG present with generalized weakness that is exacerbated by exercise (improved by rest), with or without signs of esophageal or pharyngeal dysfunction. Some dogs may present with focal clinical signs such as regurgitation (esophageal dysfunction), and rarely, dogs may present with the acute fulminating form of MG where their clinical signs progress rapidly to tetraparesis and hypoventilation. Most dogs with the generalized and focal forms of MG have a normal neurological examination. Dogs and cats with MG may have concurrent diseases such as hypothyroidism, hypoadrenocorticism and hemolytic anemia, or neoplasia (particularly thymoma), and thus, a careful physical examination and a minimum database is essential. Dogs and cats with a cranial mediastinal mass, even without clinical signs of weakness or regurgitation, should be serologically tested for MG. Many dogs with generalized MG have megaeosophagus and are at increased risk for developing aspiration pneumonia. These dogs may require serial thoracic radiographs.

The gold standard for the diagnosis of MG in dogs and cats is the presence of serum autoantibodies against muscle AChRs. This assay is species-specific, and is very specific and sensitive. Approximately 2% of dogs with generalized MG will have a negative test (so called “seronegative MG”); there are very few false positives. An AChR antibody titer greater than 0.6 nmol/l is positive in the dog. Given the large size of the AChR and the presence of many antigenic epitopes, there is no correlation between the severity of the MG and the level of the AChR antibody titer. However, there is a good correlation in an individual animal between the antibody titer and the course of the disease. The “Tensilon Test” is a clinical test used to presumptively diagnose MG, while awaiting results of the AChR-antibody test. The “Tensilon Test” may result in false positive and false negative responses. This test involves the administration of a short-acting acetylcholinesterase inhibitor (such as edrophonium) to a patient intravenously, and muscle strength is subjectively evaluated.

As with many therapies in veterinary medicine, there are no double blinded, placebo controlled trials to help guide our therapy of MG, and therefore, we have to rely on retrospective studies and clinical experience. Also, many dogs with MG go into spontaneous remission (89% in one study, Neurology 2001;57:2139-2141) on an average of 6 months after diagnosis. In dogs, anticholinesterase drugs are the cornerstone of therapy, NOT immunomodulatory drugs. Anticholinesterase drugs enhance muscle transmission by prolonging the length of time that acetylcholine is at the neuromuscular junction. The dosage is titrated to effect, to minimize adverse effects and maximize muscle strength. The most common drug used is pyridostigmine bromide. For dogs that cannot tolerate oral medications, it may be used as a constant rate infusion. In addition to anticholinesterase drugs, dogs with MG often require supportive care to treat concurrent problems such as megaesophagus and inadequate nutrition. Some dogs with megaesophagus may simply require elevated feedings, while some may require placement of a gastrotomy tube.

For this study, we require  2 tubes of refrigerated EDTA blood submitted to the UC Davis Neurology/Neurosurgery Service. Dogs may also come to UC Davis to have the blood sample collected, or the blood sample may be shipped by courier.  While there is no charge for the DNA testing, there is no financial compensation for owners participating in this study. From these collected samples, we will harvest DNA. Owners will be required to sign a consent form. If you have a patient with confirmed MG and the owner agrees to participate in our study, please contact Dr. Karen Vernau at, 530-304-9450. Free shipping is now available.Thank you in advance for your consideration and help.  We are grateful for your continued support and assistance in improving canine health.

Our shipping address is:
Dr. Karen Vernau - MG Study
Neurology/Neurosurgery VMTH UC Davis
1 Shields Ave
Davis, CA 95616