The Case: Coughing, Gagging, & Ataxia in a Young Terrier Mix

Initital Presentation

A 1-year-old spayed female terrier mix was presented for a single episode of ataxia and weakness earlier that morning with no mentation changes. The dog had been adopted from a shelter 2 to 3 months earlier, with no known medical history. Vaccinations were current, as were heartworm/flea and tick preventive medication. The dog had a history of regular coughing/gagging since adoption, which had not progressed, and bilaterally red sclerae. She was typically a quiet and anxious dog.

Related Article: Regurgitation or Vomiting?

Physical Examination

Relatively unremarkable. Completely normal neurologic examination, except for bilaterally mydriatic pupils. Sclerae were bilaterally injected. Mild pain of the cranial forelimb was elicited with palpation. The dog weighed 42 pounds, BCS 4 of 9.

Diagnostics

The patient was hospitalized for neurologic monitoring and collection of a free-catch urine sample for urine drug screening. Ataxia was not noted on any walks. The patient did not urinate during 8-hour hospitalization, and a urine sample was not obtained.

• CBC/serum biochemistry/electrolyte panel: unremarkable except for mild mature neutrophilia (WBC 16.6 × 103/mL (range, 4.0–15.5 × 103/mL)

The dog had a single  episode of short-strided, choppy hindlimb movements as well as hindlimb ataxia after 6 hours of hospitalization. Mild pelvic limb tremors were noted at the end of a walk, which resolved completely within 1 to 2 minutes. Repeat palpation of the spine resulted in apparent mild lumbosacral discomfort and pain. Neurologic/orthopedic examination findings were otherwise unchanged.

Treatment

Dog discharged for owner to monitor at home. Treatment was recommended as follows:

• Carprofen (37.5 mg q12h PO)

• Methocarbamol (375 mg q8h PO)

• Exercise restriction

• Follow-up by owner with regular primary care veterinarian for spinal/thoracic radiographs

Related Article: Interpreting Small Animal Thoracic Radiographs

Second Presentation

After discharge 4 days earlier, the dog continued to experience progressive intermittent weakness and inability to support her weight, most evident when trying to defecate. Coughing/hacking became productive and material sometimes resembled regurgitated food. The coughing initially occurred once daily or every other day but progressed to an almost continuous cough. The owner noted that the dog was now “vomiting” 6 to 7 times daily with a poor appetite, soft stools, and increased lethargy.

Physical Examination

• Depressed, dull mentation

• 5% dehydrated, pale mucous membranes

• Protrusion of both 3rd eyelids

• Moderate tonsillar enlargement bilaterally, foam visible in back of throat, reduced gag reflex

• Weakly ambulatory on all four limbs, no evidence of lameness

• Good muscle tone

• Normal cervical range of motion with no pain elicited

• No spinal pain elicited; sat with moderate sacral pressure

Diagnostics

• Routine blood analysis and urinalysis

• Hematocrit 52% (range, 36–60%)

• Total solids 6.8 g/dL (range, 5.0–7.4)

• Mild/moderate leukocytosis: WBC 20.6 × 103/mL (range, 4.0–15.5 × 103/mL)

• Lipase 3817 U/L (range, 0–205 U/L)

• Other values unremarkable

• Thoracic radiographs: consistent with aspiration pneumonia and megaesophagus Abdominal radiographs: unremarkable

• Acetylcholine receptor (AChR) antibody test and thyroid profile 6 (T4, free T4 by equilibrium dialysis [FT4ED], T3, TSH, thyroglobulin autoantibodies [AA], FT3, T3AA, T4AA) were sent to outside laboratories.

Related Article: Megaesophagus

Treatment

• Hospitalized with intravenous PlasmaLyte-A (multiple electrolyte solution)  at 75 mL/hr

• Metoclopramide (1.5 mg/lb/day CRI [34 mg/L])

• Maropitant (18 mg q24h SC)

• Ampicillin/sulbactam (560 mg q8h IV)

• Enrofloxacin (180 mg q24h IV )

• Sucralfate (1 g q8h PO)

• Food was elevated and offered directly to face

• Monitored neurologic status, respirations, coughing, vomiting

Clinical Outcome

The AchR test was positive for myasthenia gravis, and the thyroid panel was negative for hypothyroidism. The dog’s aspiration pneumonia clinically resolved, and treatment with pyridostigmine bromide was initiated (0.5 mg/kg q8h PO). The dog responded clinically and was maintained at this dosage.

The Generalist’s Opinion

Barak Benaryeh, DVM, DABVP

The clinicians in this case did an excellent job of recognizing the disease process and instituting appropriate medication. It is unfortunate that myasthenia gravis (MG) was not initially suspected, but the vague nature of the clinical signs made it difficult to suspect this disorder immediately. The initial clue was the combination of coughing and gagging with a gait abnormality. Keeping this dog under hospital observation was a wise choice and is generally an excellent clinical tool in cases where a disease process is not immediately evident. With only a single episode of mild ataxia exhibited, it was not inappropriate to discharge the patient for at-home observation. Aspiration pneumonia was an unforeseeable and regrettable sequela.

Appropriate Diagnostics

In cases such as this, in which a patient presents with a recurrence of clinical signs, a full workup is in order. On the second visit the clinician recognized MG as a strong possibility and sent off the appropriate test. The acetylcholine receptor (AChR) test is the ideal and least invasive for this disorder. False positives have not been reported and the false negative rate is as low as 2% to 5%. In the case of a negative test, a muscle biopsy or electrophysiologic tests can be performed if suspicion remains high. An edrophonium (Tensilon) response test is an alternative, but edrophonium is hard to come by. In addition, the test is difficult to interpret and rarely leads to a definitive diagnosis. Other rule-outs for intermittent weakness include cardiac disease (intermittent arrhythmias), atypical seizure disorders, thyroid disorders, or some lesser known neurologic diseases that are often breed specific. Holter and event monitors are now an available technology in veterinary medicine and can be used if cardiac disease is suspected but an arrhythmia is not recognized during the examination.

More than 50% of acquired MG patients will spontaneously recover within 1 to 18 months of diagnosis. Pyridostigmine is the ideal drug choice. This case demonstrates good clinical judgment. Although the disease was not recognized at the first presentation, when the dog was presented again all appropriate steps were taken. 

Barak Benaryeh, DVM, DABVP, is the owner of Spicewood Springs Animal Hospital. He graduated from University of California–Davis School of Veterinary Medicine in 1997 and completed an internship in Small Animal Medicine, Surgery, and Emergency at University of Pennsylvania. Dr. Benaryeh has also taught practical coursework to first-year veterinary students and was a primary veterinary surgeon for the Helping Hands Program, which trains assistance monkeys for quadriplegic people. Dr. Benaryeh is certified by the American Board of Veterinary Practitioners in Canine and Feline Practice.

The Specialist’s Opinion

Mark Troxel, DVM, DACVIM (Neurology)

This case report highlights the difficulty of making a diagnosis of acquired myasthenia gravis (MG) in dogs, especially early in the course of clinical signs.  Acquired MG is an immune-mediated disorder in which serum autoantibodies are directed against the acetylcholine receptors (AChR) at the skeletal neuromuscular junction. MG can be very difficult to diagnose because it can mimic other disorders, such as neuropathic, other myopathic, or even orthopedic diseases. The “classic” signs of regurgitation and generalized weakness with exercise intolerance often are not present in myasthenic patients. In one study, 43% of dogs with confirmed MG did not have clinically detectable weakness. Of the remaining 57% with generalized weakness, 13% did not have esophageal/pharyngeal dysfunction. Acquired MG should be on your list of differential diagnoses when focal or generalized weakness is present or in patients with megaesophagus.

Initial Considerations

The initial presentation of this patient did not provide clear clues that the patient had MG, but some factors would have increased my index of suspicion. The history of regular coughing/gagging over a course of 2 to 3 months could have been caused by pharyngeal weakness or intrathoracic disease. Thoracic radiographs to rule out pulmonary disease would have been useful. It’s possible that megaesophagus would have been present at that time, which would have changed the direction of diagnostics and treatment.  

The case presentation describes an episode of short-strided, choppy hindlimb movements with ataxia as well as mild pelvic limb tremors at the end of a walk that resolved completely within 1 to 2 minutes. These signs can be associated with lower motor neuron (LMN) spinal cord disease, neuromuscular disease, or orthopedic disease. Given the detected lumbosacral pain, it is logical to conclude that this episode could be due to spinal/orthopedic disease. While the presumptive diagnosis at the time of initial discharge is not mentioned, the treatment plan suggests that the veterinarian was pursuing a course of medical management for spinal cord disease.

I am frequently presented with young patients with spinal pain and/or weakness/ataxia. In patients up to one year of age, intervertebral disk disease (IVDD) is very uncommon, so my differentials include trauma, inflammatory/infectious spinal cord disease, vertebral/spinal cord malformations, and other less common diseases.

Clues at Second Presentation

By the time the patient was brought back in for reevaluation, the clinical signs had progressed to fairly obvious signs of generalized neuromuscular disease. Given the patient’s signalment, acquired MG would be the most likely differential diagnosis: Acquired MG has a bimodal age distribution and, like other immune-mediated diseases, is more common in females. The presence of megaesophagus with aspiration pneumonia on thoracic radiographs further supports a preliminary diagnosis of MG.

For the most part, I agree with the author’s diagnostic workup with some minor changes: An edrophonium challenge (Tensilon test) could have been performed. While it lacks specificity and sensitivity, a significant improvement in strength after the challenge further supports the working diagnosis of MG. If unavailable at your practice, I would consider referral to a specialist for the test and possibly additional diagnostics/treatment. While hypothyroidism can cause generalized weakness, megaesophagus, and pharyngeal weakness, it is uncommon to rare in dogs only one year of age. From a client cost perspective, I would have submitted only a total T4. Admittedly, a low level could have been due to euthyroid sick syndrome and would have required follow-up, but a normal level would have potentially saved the significant cost of other diagnostics and/or treatment. Finally, abdominal ultrasound is a more sensitive test to screen the abdomen for a possible predisposing cause for MG.

The gold standard for diagnosing acquired MG is detection of anti-AChR antibodies. To my knowledge, there is only one laboratory in the United States that performs this test and it takes 5 to 7 business days to get the results. False positives are rare. Approximately 2% of dogs with confirmed MG will be seronegative. In these cases, other diagnostics are required to diagnose the condition, such as repetitive nerve stimulation, single fiber electromyography, or whole muscle biopsy to examine the neuromuscular junction.

Treatment & Prognosis

Therapy for MG is centered on prevention and treatment of aspiration pneumonia and alleviating the clinical signs of neuromuscular weakness. Pyridostigmine is a long-acting cholinesterase inhibitor that alleviates neuromuscular weakness by blocking the breakdown of acetylcholine in the neuromuscular junction, allowing it to bind to available receptors. It is unclear from the report when the medication was started. It should be started as soon as possible after the preliminary diagnosis of MG is made, even while awaiting AChR antibody titer results. In patients with significant regurgitation, injectable neostigmine should be used initially.

Using immunosuppressant medications is controversial in veterinary medicine. Some neurologists recommend their use since this is an immune-mediated disease, but immunosuppressants should be used very cautiously due to the high risk of aspiration pneumonia. Prednisone often is prescribed with other immune-mediated disorders, but at high doses it can cause neuromuscular weakness, exacerbating the clinical signs in myasthenic patients. Other immunosuppressive medications (eg, azathioprine, cyclosporine, mycophenolate) have also been used for treating MG. It is important to note that in one study there was a high rate (88%) of spontaneous remission (average 6.4 months) in dogs with acquired MG.  As a result, immunosuppressive medications may not be required if there is a good response to initial therapy.

I usually start with pyridostigmine for 2 to 3 days to see if there is a positive response before considering immunosuppressive medications. Other nonspecific treatments include antibiotics to treat aspiration pneumonia, elevated feedings, hydration, and nutritional support. In patients with megaesophagus, elevated feedings are very important and the patient should be held vertically for 5 to 10 minutes after eating to encourage food to pass into the stomach. For larger patients, a “Bailey chair” can be built to help hold the patient.

The prognosis for acquired MG has been reported as guarded to poor, especially in patients with megaesophagus and aspiration pneumonia. However, with early diagnosis, aggressive treatment, dedicated owners, and close monitoring, patients can do very well. Successful treatment of these patients is highly rewarding so a concerted effort should be made to treat the patient.

Mark Troxel, DVM, DACVIM (Neurology), graduated from the Iowa State University College of Veterinary Medicine in 1999. Following a rotating internship and a medicine specialty internship, he went on to complete a neurology residency at the University of Pennsylvania. Currently a staff neurologist/neurosurgeon at the Massachusetts Veterinary Referral Hospital, he has published numerous articles and book chapters in the veterinary literature.