Myasthenia gravis has been redefined in human medicine and efforts to do the same in veterinary medicine are currently underway.
What does myasthenia gravis mean? “Myasthenia” means muscle weakness. “Gravis” means severe, grave, or serious.
Previously, myasthenia gravis was grouped into two categories: congenital (hereditary) and acquired. The easiest way to differentiate the two were the absence of autoantibodies in the congenital form versus the presence of autoantibodies in the acquired form.
Nowadays, the term “myasthenia gravis” only applies to the acquired form. Thus, myasthenia gravis refers to the body producing autoimmune antibodies (autoantibodies) that block, alter, or destroy the receptors for the acetylcholine (neurotransmitter) at the neuromuscular junction, which prevents the muscle from contracting.
Quick aside…As a point of reference, think of the knee jerk reflex test doctors perform by tapping the knee with a rubber hammer. One of the items they are checking is the neuromuscular junction response which is mediated by acetylcholine.
The congenital form of myasthenia is now referred to as congenital myasthenic syndromes. Previously, it was thought to be simply a deficiency of the acetylcholine receptors because no autoantibodies were present.
Scientists are discovering in dogs that each of the congenital syndromes are still all autosomal recessive traits (inherited mutated genes from both parents) and cause muscle weakness. However, the genes affected, mutated or deleted are different and usually differ by breed.
For instance, the classic “deficiency of acetylcholine receptors” is seen in Jack Russell Terriers, but this deficiency is not commonly found in affected Labrador Retrievers. Rather, Labrador Retrievers typically have a different cause of muscle weakness due to another component of the neuromuscular junction called acetylcholinesterase (which breaks down acetylcholine) deficiency, and they only have a slight decrease in acetylcholine receptors.
Golden Retrievers can also have an acetylcholinesterase deficiency, but the mutation involves a different gene than that in Labrador Retrievers.
Why are these genetic distinctions important? Because they help gene therapy and proper symptomatic treatment.
Symptoms
The symptoms – which are progressive – can vary from dog to dog.
- Pharynx laxity – changes occur to their bark
- Limb muscle weakness and stiffness – Affected dogs will usually exhibit shortened strides and stiffening limbs during exercise, but also have muscle weakness after exercise. As the disease progresses, the periods of exercise exertion shorten while rest time lengthens. This can lead to paralysis.
- Facial weakness – inability to blink; drooping lip; and facial paralysis
- Drooping tail
- Trouble controlling urine stream or squatting
- Lethargy
Acquired Myasthenia Gravis
Acquired myasthenia gravis is an immune-mediated (autoimmune) neuropathy (disease of the nerves). As a reminder, the body produces autoantibodies that attack and destroy the acetylcholine receptors specifically.
Megaesophagus is typically only experienced by dogs that suffer from acquired myasthenia gravis. Megaesophagus is the relaxing of the esophageal muscle so that food cannot be pushed by normal muscle contraction down into the stomach. Dogs can develop aspiration pneumonia from inhaling regurgitated food. Dogs are typically fed from a dog highchair (also known as a Bailey Chair.)
Like most immune-mediated diseases, we have not identified which specific outside forces (food, infections, chemicals, vaccines, environment, etc.) trigger the body to produce these antibodies that attack itself, but believe there is a genetic component. In the instance of myasthenia gravis, it might be an overdeveloped abnormal thymus gland.
A dog’s thymus gland functions similarly to that in humans. It is a vital organ in the development of the immune system since it builds up the T-lymphocytes (T-cells) to help fight infection and other immune challenges. Once this developmental process is complete, the thymus stops active production and stays dormant. In humans and dogs with myasthenia gravis, it has been observed that the thymus gland remains large and is abnormal (forms a thymoma).
Researchers believe the thymus gland may give incorrect instructions to the developing immune cells, ultimately resulting in autoimmunity and the production of the acetylcholine receptor antibodies, thereby setting the stage for the attack on neuromuscular transmission.
With myasthenia gravis, we break it down further into three groups:
- Mild or Focal – only one body part is afflicted, and it is usually the esophagus
- Moderate Generalized – limb weakness with or without megaesophagus
- Severe Generalized or Acute Fulminating – rapidly progressive and usually fatal
Diagnosis
Both acquired myasthenia gravis and congenital myasthenic syndromes can be fatal. One of the reasons may be a delayed diagnosis particularly in the case of acquired myasthenia gravis – so treatment may be delayed or inappropriate treatment is given.
Several DNA tests exist to diagnose congenital myasthenic syndromes.
A blood test exists for acquired myasthenia gravis. This blood test, AChR, checks for the autoantibodies that are destroying the acetylcholine receptors. Remember, the congenital form does not have the autoantibodies. The AChR specificity rate is 98%.
If the veterinarian is fairly certain that your dog lands within this 2% zone, other tests are available such as the Tensilon Response Test to see if the muscles move after administering edrophonium chloride (an acetylcholinesterase inhibitor), and electrodiagnostic testing to see if electrodes stimulate the muscles to respond at various levels. They can also retest with the AChR test a couple of weeks later.
Before performing these secondary or follow-up tests, please also consider thyroid disease as a possible cause of these symptoms. Thyroid dysfunction can cause neuropathies such as megaesophagus and muscle weakness. Indeed, hypothyroidism could be concurrent with myasthenia gravis. Thus far, we believe they are separate conditions and that one does not precipitate the other. Regardless, I recommend a complete thyroid panel that measures the hormones T4, FT4, T3 and FT3, and the thyroid autoantibody, TGAA, at either Hemopet’s Hemolife Diagnostic Laboratory, Michigan State University, or another veterinary reference diagnostic laboratory.
Treatment
Treatment outcomes for acquired myasthenia gravis or congenital myasthenic syndrome are variable.
Congenital
One of the “go to” therapies for dogs is acetylcholinesterase inhibitors. As we previously discussed, acetylcholinesterase is already deficient in certain breeds with certain congenital myasthenic syndromes. So, if acetylcholinesterase is further inhibited, the effects can exacerbate the myasthenic condition or have no effect.
For dogs who have other types of congenital myasthenic syndromes, acetylcholinesterase inhibitors may prove useful, but results are usually transient due to drug tolerance.
Acquired
Once diagnosis is confirmed, veterinarians can try acetylcholinesterase inhibitors like pyridostigmine bromide. Basically, the body has a naturally occurring acetylcholinesterase enzyme that breaks down acetylcholine, which is needed to put the brakes on the neurotransmission. Think about it, if acetylcholinesterase did not exist, we would have muscle spasms or facial tics all the time. So, if we stop or slow the production of it, the acetylcholine has time to replenish and do its job.
Use of other drugs such as glucocorticoids (a class of corticosteroids) and other immunosuppressive drugs is controversial and inadvisable. They can enhance certain symptoms like muscle weakness or cause side effects like weight gain, instead of effectively treating the condition.
Antibiotics are often prescribed for a secondary condition such as aspiration pneumonia. However, exacerbation of myasthenia gravis can occur with the use of fluoroquinolones (a class of antibiotics including enrofloxacin) in humans and dogs alike.
A thymoma can invade surrounding tissues and take up space in the thorax. In these instances, thymus removal may be recommended. However, general anesthesia is necessary and already poses a substantial risk for dogs with myasthenia gravis. In and of itself, the surgery can cause a clinically relevant postoperative exacerbation of muscle weakness, which is thought to be the result of surgical stress.
The most innovative procedure to date is therapeutic plasma exchange (TPE). Basically, the plasma containing the autoantibodies is removed and exchanged with fresh healthy canine donor plasma. However, it is not a cure for myasthenia gravis, expensive, and usually requires going to a veterinary research institution.
Other supportive care really comes down to a daily ritual depending upon what part of the body is affected. For instance, megaesophagus requires fine-tuned care that includes slow eating, swallowing small chunks of food whole, lifting the food and water bowls to chest height, and possibly using a Bailey Chair to sit the dog in an upright position.
Myasthenia gravis demands patience and commitment from the pet caregiver. Remember, it is a progressive condition that does not have a cure, but we can try to slow the progression and side effects with the right supportive care and medications for a longer, quality life.
References
Forgash, Jennifer T et al. “Clinical features and outcome of acquired myasthenia gravis in 94 dogs.” Journal of veterinary internal medicine vol. 35,5 (2021): 2315-2326, doi:10.1111/jvim.16223, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478050/.
Guzman, Karen Marina Hernandez, and Kenneth Harkin. “Suspected Fluoroquinolone-Induced Exacerbation of Myasthenia Gravis in Dogs.” Journal of the American Animal Hospital Association vol. 59,5 (2023): 249-254, doi:10.5326/JAAHA-MS-7353, https://pubmed.ncbi.nlm.nih.gov/37708471/.
Kumar, Rajesh et al. “Therapeutic Plasma Exchange in the Treatment of Myasthenia Gravis.” Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine 19.1 (2015): 9–13, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296418/.
Mignan, Thomas et al. “Classification of myasthenia gravis and congenital myasthenic syndromes in dogs and cats.” Journal of veterinary internal medicine vol. 34,5 (2020): 1707-1717, doi:10.1111/jvim.15855, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517852/.
Rinz, Caitlin J et al. “A COLQ missense mutation in Labrador Retrievers having congenital myasthenic syndrome.” PloS one vol. 9,8 e106425. 28 Aug. 2014, doi:10.1371/journal.pone.0106425, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148433/.
Tsai, Kate L et al. “Congenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation.” Journal of veterinary internal medicine vol. 34,1 (2020): 258-265, doi:10.1111/jvim.15667, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979411/.
Originally Published: January 15, 2017
Updated: June 25, 2024