Neurology, What's Your Diagnosis?

What’s Your Diagnosis?

by Dr. Andrew Barker, Neurology, Toronto Veterinary Emergency Hospital

An 8-month old male intact German Shepherd presented to the Toronto Veterinary Emergency Hospital for an approximate two-day history of hind-limb deficits. The dog slipped while playing three days before; however, he was walking normally and seemed comfortable. The following day the dog was normal in the morning, and in the afternoon appeared to become slightly wobbly in the back end. The owners did not feel that he was painful. The following day, signs progressed to the point where the patient was unable to use stairs. The owners reported no vomiting; however, during the client interview the patient regurgitated foam twice. When further questioned, the owner indicated that this had also happened at home several times. The patient was fully up to date on annual vaccines, and had no significant medical issues in the past.

At presentation, the patient was bright, alert, and responsive. Vital parameters and a general physical examination were within normal limits. A neurological examination found the dog to have marked weakness in the hind limbs when walking and a crouched posture in the hind limbs.  Exercise intolerance and development of weakness in forelimbs were also noted within a few minutes of walking. The patient appeared to improve after several minutes of rest. Postural reactions were found to be normal in all limbs, as were spinal reflexes and a cranial nerve examination. No appreciable pain on spinal palpation or cervical range of motion was found.

What is your neurological lesion localization?

What is your differential list?





Lesion localization and differential list

Based on the evidence of weakness without proprioceptive deficits, as well as exercise intolerance, a disease process affecting the neuromuscular junction, a diffuse myositis, or a polyneuropathy are the most likely. Myasthenia gravis is the most likely cause given the clinical signs of weakness, exercise intolerance, and regurgitation. Polyradiculoneuritis or “coonhound paralysis” as well as a diffuse myositis are possible but less likely with regurgitation.

Myasthenia gravis is a disorder of neuro-muscular transmission. Two forms exist, a congenital and acquired form. The congenital form is uncommon, and has a variety of forms and suspected modes of inheritance. The acquired form is an immune-mediated disorder that can either be primary or a paraneoplastic disorder. The paraneoplastic disorder makes up only a small percentage of cases (<5% dogs, 25% cats). The most commonly identified neoplasia is thymoma. Other types of neoplasia have also been associated with the disorder including osteogenic sarcoma, cholangiocellular carcinoma, cutaneous lymphoma, and anal sac adenocarcinoma. The acquired form has two types. Focal is less common accounting for 43% of cases. In these cases, limb weakness, and exercise intolerance are not observed.

Megaesophagus is seen in approximately 77% of cases, facial weakness in approximately 33%, and laryngeal/ pharyngeal weakness in approximately 44%.  In the generalized form, the majority (80-90%) have megaesophagus. There is a very high prevalence of aspiration pneumonia (95%). Other clinical signs include exercise intolerance, general weakness, and a fatigable palpebral reflex. Patients usually will walk normally for brief periods before gradually sinking in the hind limbs and progressing to affect the forelimbs. Given a period of rest the patient will return to normal for a brief time.

Diagnosis

The most commonly used in-clinic test is an intravenous injection of a short acting anticholinesterase inhibitor edrophonium chloride, the “Tensilon Test.” By blocking the action of the enzyme that breaks down acetylcholine there is an increase in the available acetylcholine to bind the receptors that are not bound by an antibody. A positive test result can be highly suggestive of myasthenia; however false positives with other neuromuscular disorders such as botulism, and false negatives with the fulminating type of myasthenia as not enough receptors remain unbound, do occur. For a video displaying a positive Tensilon test, see the Cornell University College of Veterinary Medicine website for “Video Resources for Veterinary Neuroanatomy and Clinical Neurology, Fourth Edition”:

http://www.neurovideos.vet.cornell.edu/Video.aspx?vid=05-04)

The gold standard for diagnosis is the acetylcholine receptor antibody titer. This is performed by a blood sample. Serial monitoring of the titer level can also be used to determine if the patient is approaching, or in, remission.

Treatment and Prognosis

Medical therapy involves the use of a cholinesterase inhibitor such as pyridostigmine bromide to increase the amount of available acetylcholine at the neuromuscular junctions. Due to the potential for a cholinergic crisis, the initial dosing is at the lower range and gradually increased as required. Patients should be monitored for improvement in their mobility, and the presence of side effects including “SLUD” which stands for salivation, lacrimation, urination (accident in the house), and defecation/ diarrhea. A balance should be attempted to find the most effective dose for as normal an energy level as possible with as few or as manageable side-effects as possible. The use of corticosteroids and other immunosuppressive medications is controversial, and their use will vary from clinician to clinician. Immunosuppression may help alleviate clinical signs; however, the continued risk of aspiration pneumonia due to persistent megaesophagus is a concern. Except for fulminating myasthenics the majority of patients respond to use of acetylcholinesterase inhibitors.

Nursing care and the Bailey chair

Feeding while in a vertical body position and maintaining it for several minutes may reduce the risk of aspiration pneumonia. The use of a “Bailey Chair” may be helpful particularly in larger patients.

Particularly for fulminating myasthenics, and those recently started on an acetylcholinesterase inhibitor, good nursing care is essential. Patients must be assisted to eat and drink, and for positioning to urinate and defecate. Patients require soft padded bedding to prevent pressure sores, and should be turned every 4-6 hours if unable to do so themselves.

Prognosis

Despite most patients responding to medications, the prognosis is guarded to grave. Approximately 60% of myasthenic dogs will not survive 6 months, with the majority in one study dying or being humanely euthanized within two weeks. This is largely due to the development of aspiration pneumonia, although a failure to respond to medications, unacceptable side effects, and medication costs are also causes for humane euthanasia.

Spontaneous remission has been found to occur in patients with the average occurring at 6 months (range 1-18 months). The determination of remission can be made based on lack of clinical signs when medications are decreased, and more accurately by monitoring the acetylcholine receptor antibody titer and observing a return to normal levels.

Returning to the patient

The patient had a marked positive response to an endrophonium test (0.1 mg/kg of edrophonium) and was strongly ambulatory for approximately two minutes before rapidly returning to a weakened gait. Thoracic radiographs (Figure 1 and Figure 2) confirmed the presence of megaesophagus.

Figure 1: A right lateral thoracic radiographBarker WYD Image 1

Figure 2: The same right lateral thoracic radiograph. The arrows are indicating the dorsal aspect of the dilated esophagusBarker WYD Image 2

The owners declined performing the receptor antibody titer and the patent was started on pyridostigmine bromide at a dose of 2 mg/kg twice daily. Instructions were to feed canned food, made into meatballs. The patient was to be fed with his upper body elevated, and was to remain in an elevated position for 20 minutes after eating. One week after starting the medication the patient had improved but was only able to walk short distances. The pyridostigmine was increased to 2.25 mg/kg twice daily. Clinical signs improved to near normal activity level. The patient developed occasional diarrhea, but the owners considered this acceptable. At a recheck examination eight months after initial diagnosis the patient had done very well and appeared to have normal activity level. The owners reported no persistent diarrhea or evidence of regurgitation. A gradual tapering of the pyridostigmine occurred with a reduction in dose on a weekly basis. The patient was able to be taken off medication and at the time of writing remains well.

References
DeLahunta A. Glass E. Lower Motor Neuron: Spinal Nerve, General Somatic Efferent System in Veterinary Neuroanatomy and Clinical Neurology, 3rd Edition. Saunders Elsevier. St. Louis, Missouri. 2009.
Dewey CW, Bailey CS, Shelton GD, Kass PH, Cardinet GH 3rd. Clinical forms of acquired myasthenia gravis in dogs: 25 cases (1988-1995). J Vet Intern Med. 1997;11:50-7.
Hague DW, Humphries HD, Mitchell MA, Shelton GD. Risk Factors and Outcomes in Cats with Acquired Myasthenia Gravis (2001-2012). J Vet Intern Med. 2015; 29:1307-12.
Shelton GD, Lindstrom JM. Spontaneous remission in canine myasthenia gravis: implications for assessing human MG therapies. Neurology. 2001; 57:2139-41.
Shelton GD. Myasthenia gravis and disorders of neuromuscular transmission. Vet Clin North Am Small Anim Pract. 2002; 32:189-206.

About the Author:

Dr. Andrew Barker was born and raised in Toronto and attended the University of Guelph for an undergraduate degree in Biological Sciences and graduated in 2009 from the DVM program at the Ontario Veterinary College. He completed a rotating medicine and surgery internship at the Atlantic Veterinary College in PEI followed by a neurology internship at Canada West Veterinary Specialists in Vancouver, BC.  Following the completion of a neurology residency at Iowa State University, Andrew worked as an Assistant Professor (Neurology and Neurosurgery) at the Ontario Veterinary College, University of Guelph.  Andrew become a diplomate of the ACVIM (Neurology) in 2017.

Andrew joined the TVEH team in October, 2015. His professional interests include spinal surgery, and non-infectious conditions of the canine central nervous system.

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