Canine Myasthenia Gravis Update

What is myasthenia gravis?

Myasthenia gravis (MG) is a neuromuscular disease caused by congenital or acquired causes. Acquired MG is caused by an attack against the acetylcholine receptor on the muscle or  the muscle specific kinase (MUSK) protein. Acquired MG will be the focus of this TidBit today. 

How does myasthenia gravis present clinically?

Focal, generalized and fulminant forms have been described. Focal MG results in weakness of 1 or more muscle groups (ex: esophagus or pharynx) and does not cause limb weakness. Generalized MG results in limb weakness, with or without (usually with!) megaesophagus and pharyngeal weakness and the fulminant form causes acute severe flaccid paresis or paralysis often requiring hospitalization and intravenous intervention. 

How is myasthenia gravis diagnosed?

Acquired MG is diagnosed by a combination of clinical signs, positive acetylcholine receptor antibody titer and/or positive response to edrophonium challenge. A positive acetylcholine receptor antibody titer is considered the gold standard diagnostic tool.  Seronegative MG is reported in about 2% of cases and likely represents dogs with immune attack against the MUSK protein rather than the acetylcholine receptor. Edrophonium is a short acting acetylcholinesterase inhibitor that can be used in the preliminary stages of diagnosis. Animals are administered a small dose of edrophonium and monitored for clinical signs of improved strength. This test is not advisable for use in obtaining a diagnosis of focal MG. It is important to note that dogs with other neuromuscular diseases may have a positive edrophonium challenge therefore it should not be used as a sole diagnostic tool. 

What is the treatment for myasthenia gravis in dogs and cats?

Acquired MG is most often treated with an oral, long acting acetylcholinesterase (pyridostigmine). Signs of overdose are similar to signs of acquired MG (SLUD plus weakness) therefore it is recommended to start at a lower dose and slowly increase the dose over 1-2 weeks until clinical signs resolve. Immunosuppression has been used for pets with focal or generalized MG however the risk of secondary pneumonia is higher with immunosuppression and the clinical improvement does not appear to be better than with pyridostigmine administration therefore it is rarely recommended. 
Acquired MG will often result in remission within 8 months of the initial diagnosis. If remission is not achieved, follow-up testing for concurrent diseases that could trigger MG is recommended. This includes a thyroid panel (for thyroiditis), chest radiographs and abdominal ultrasound for a cancer screening. 

Thanks for reading! I hope you have a great week and I look forward to working with you soon. 

Flaccid Paralysis: Diagnosis and Treatment

Last week we discussed a case of flaccid paralysis that was localized to the neuromuscular system, specifically either neuromuscular junction or peripheral nerve. This week, we'll talk briefly about pursuit of diagnostic testing and treatment for these cases.

Diagnostic Testing
This group of diseases is a diagnostic challenge. In academic, or specialty clinics, electrodiagnostic testing may be recommended to look for hallmark changes amongst these group of diseases. Aside from not being readily available, electrodiagnostic testing is also imprecise when attempting to differentiate between this group of diseases. So what do we do? We attempt to differentiate based on history and physical exam findings. For example, animals with polyradiculoneuritis (Coonhound paralysis) are often hyperesthetic with normal bladder function and may, or may not have a history of contact with wildlife (Racoon). By contrast, those with botulism often have urinary retention, reduced mentation and mydriasis. Dogs with tick paralysis rarely have cranial nerve deficits and may have the mildest signs of the group. Coral snake bite results in rapid death (and is only found in the southern states). Organophosphate toxicity is frequently discovered when reviewing the history. Signs of SLUD (see below) or a history of exposure to organophosphate containing products can help guide this diagnosis. Blood cholinesterase levels can be measured (I've never done it) but they aren't reliable once the neurologic signs are apparent.

Treatment Options
Clinical suspicion can only get us so far. At some point we start treatment for the most likely cause. I will often recommend application of a tick product (example: frontline), even if a "tick check" is negative for the patient. Tick paralysis typically begins to improve within 24 hours after application of the product, further increasing your suspicion of the cause.

Polyradiculoneuropathy can progress to respiratory failure so referral for ventilator support is critical for dogs exhibiting reduced cutaneous trunci reflexes. Evaluation of CO2 levels can help you detect if the animal is not ventilating appropriately. No specific treatment is available for polyradiculoneuropathy. Supportive care with assistance to eat, drink and nursing care to maintain cleanliness are critical during the recovery period. These animals can void voluntarily, however they cannot move away from soiled bedding therefore bedsores are a high risk for this patient population. Physical rehabilitation is helpful for recovery so please get these dogs to PT as soon as you can! Recovery may take 4 to 6 months in dogs with severe disease, or 1-3 months in dogs with mild cases.

Botulism is diagnosed with detection of the toxin in serum, feces or gastric contents. This is extremely hard to do, and rarely is a confirmed diagnosis made. Supportive care with fluid support, urinary bladder catheterization, and management of secondary infections may help reduce the risk of death however Botulism is commonly fatal. An older report (Bruchim Y, The Vet Record 2006) describes the rare successful treatment of a mixed breed dog with botulism utilizing supportive care measures.

My experience with coral snake envenomation is limited to only a few cases during my residency at the University of Florida. Each case had a fatal outcome so I don't have a lot of treatment recommendations or supportive care ideas. If you live in the southern US - reach out to your local neurologist for additional help if you encounter a case.

Organophosphate toxicity results in paralysis from blockade of the acetylcholinesterase in the body, thus causing prolonged exposure to AcH at the receptor. This results in acute SLUD (salivation, lacrimation, urination, and defecation) followed by muscle weakness. No specific treatment is available. Atropine does not help once the SLUD has passed and the dog has progressed into the neuromuscular weakness signs. Supportive care, again, is the way to go. This may include ventilator support, along with nursing care and nutritional support. Signs may improve within 7 days after onset, but death is common. (Hopper, K, et al. JVECC 2002)

Whew! These cases are tough! Sometimes we "treat for the treatable" causes because that is all we can do. Keep up the good work and thanks for including me in your case management. I love working with you on the "easy" and the "hard" stuff!