NEUROMUSCULAR CASE OF THE MONTH - OCTOBER 2000

Dysautonomia in dogs
Contributed by Dennis P. O’Brien DVM PhD
Associate Professor of Veterinary Neurology
Department of Veterinary Medicine and Surgery
College of Veterinary Medicine
University of Missouri

Dysautonomia is characterized by degeneration of neurons in the autonomic ganglia with associated failure of sympathetic and parasympathetic functions. Neurons are diminished or absent in the ganglia of affected dogs and replaced by gliosis. There is little inflammation present. The cause is unknown. More recently an increasing number of cases of canine dysautonomia have been diagnosed in the midwest United States (Longshore et al., 1996). This section will describe the diagnostic and therapeutic approaches we have applied to these cases at the University of Missouri, Veterinary Medical Teaching Hospital. Dysautonomia has been diagnosed primarily in young adult dogs (median age 14 months with a range from 8 weeks to 10 years of age). Although Labrador retrievers were slightly over-represented, a wide variety of breeds have been affected. The most common presenting complaints in affected dogs have been dysuria, regurgitation, purulent nasal discharge, photophobia, anorexia, and weight loss (Table 1). The duration of clinical signs averaged about 2 weeks.

Figure 1. Normal autonomic ganglia are packed with neurons (left). In dysautonomia, the neurons die and are replaced with scar tissue (right).

History and Clinical Signs Physical exam findings reflected primarily loss of parasympathetic functions although sympathetic dysfunction was also present. Pupillary light responses were absent with normal vision, and the pupils varied from maximally dilated to midrange. Ocular and oral mucous membranes lacked normal secretion. The dogs would frequently posture to urinate, but they produced little urine. On abdominal palpation, the bladder was distended, and pain was occasionally noted. Sympathetic dysfunction was often less obvious. Loss of sympathetic as well as parasympathetic innervation of the iris may have contributed to the midrange pupils seen in some dogs. Other signs of Horner’s syndrome such as elevated third eyelids, ptosis and enophthalmos were often present. The distended bladder was easily expressed suggesting diminished sphincter tone. Heart rate and blood pressure were generally in the low end of the normal range, but did not increase with stress or excitement. The only sign of somatic motor system involvement was decreased anal sphincter tone; this was present in most dogs. Myotatic and withdrawal reflexes, sensory perception, and postural reactions were normal. Secondary effects of the autonomic dysfunction such as aspiration pneumonia and lethargy soon developed. Rhinitis secondary to dry mucous membranes and/or regurgitation was a common finding. Weight loss was often dramatic with many of the dogs presenting cachexic. No consistent changes were observed in the complete blood counts, urinalyses, serum chemistries, or cerebrospinal fluid analyses.

Figure 2. Nasal discharge, elevated third eyelid & dilated pupils are typical of dysautonomia Figure 3. Affected dogs lose weight dramatically. The bladder is distended and easily expressed.

Pharmacologic testing of the pupils is probably the best single test for confirming the diagnosis. Pilocarpine ophthalmic solution (Isopto Carpine 1%, Alcon) is diluted to 0.05% with normal saline and 1-2 drops placed in one eye. Pupil size is then observed every 15 minutes. Dogs with dysautonomia generally show a rapid constriction of the pupils. Even at the 0.05% dilution, some normal dogs may show some constriction of the pupils, but it will take 45-60 minutes. If no response is seen 90 minutes after instilling the 0.05% solution, the test is repeated with full strength (1-2%) pilocarpine. Since drugs such as atropine produce their effects by blocking cholinergic receptors, dogs who have parasympathetic signs due to such drugs or toxins should not respond to even the full strength pilocarpine solutions.

Thoracic radiographs can confirm the presence of megaesophagus and detect secondary aspiration pneumonia. Abdominal radiographs may demonstrate a distended urinary bladder and occasionally ileus. Alternatively, ultrasound can be used to document the distended bladder, ileus and lack of normal gastrointestinal motility. Attempts to urinate will have little effect on bladder volume. The dog can then be tested with a low dose (0.0375 mg/kg SQ) of bethanechol (Urecholine, Merck Sharp & Dome) and bladder volume re-evaluated with ultrasound. Emptying of the bladder with low-dose bethanechol would suggest denervation supersensity. Some affected dogs have not responded to bethanechol, presumably due to secondary detrusor atony.

Confirming sympathetic involvement is more problematic. Orthostatic hypotension can be documented by measuring blood pressure in the thoracic and pelvic limbs with the dog first in lateral recumbency and then tilted at a 30-45 degree angle. In a normal dog this has little effect on blood pressure. In the dogs with dysautonomia, blood pressure drops in the elevated limbs and increases in the down limbs. Heart rate is usually within normal limits, but does not increase as expected when the blood pressure drops. Provocative challenges with drugs that affect heart rate and blood pressure are not recommended due to the risk of deleterious effects. The wheel and flair response to histamine depends upon normal sympathetic innervation of the blood vessels. Thus dogs with dysautonomia should not respond normally to intradermal histamine, but this has not been evaluated systematically.

Therapy Since the cause of dysautonomia is still unknown, we are limited to symptomatic therapy. Cholinergic drugs can help relieve some of the signs of parasympathetic dysfunction. Bethanechol (1.25-5 mg q 12 h) given orally provided some improvement in secretion and urination, but better results have been seen with subcutaneous administration (started at 0.0375 mg/kg q 12 h and slowly increased as necessary). Frequent expressing of the bladder will be necessary if the bladder does not empty adequately with the bethanechol. Pilocarpine eye drops will stimulate tear production and relieve photophobia. Use of artificial tears is also beneficial. Gastrointestinal motility can be improved by the use of prokinetic drugs such as metaclopramide (Sidmack Laboratories). Humidifying the air can help relieve some of the dryness to the oral and nasal mucous membranes. Parenteral nutrition may be necessary to prevent the development of cachexia. The prognosis in dysautonomia is grave. In the feline epidemic, mortality was about 70% (Edney et al., 1987) and our experience to date with the canine disease suggests a similar high mortality. Animals who survived have been largely left with permanent dysfunction and require intensive nursing care. One dog recovered after 3 months with only dilated pupils and occasional regurgitation as residual signs. Fortunately, the disease appears to still be uncommon, but the increasing number of cases seen in the midwest raises the concern that an epidemic such as occurred in cats in England could be on the horizon.

Figure 4. Dilation of the esophagus (arrows) can be seen on thoracic radiographs

Table 1
Historical and physical examination findings in 11 dogs with necropsy confirmed dysautonomia.

Historical and/or physical finding	Number of dogs affected/ Number in which evaluation was recorded
Dysuria	11/11
Distended urinary bladder	10/10
Mydriasis	11/11
Absent pupillary light reflex	11/11
Dry mucous membranes	10/11
Weight loss	8/10
Decreased Schirmer tear test (<15mm/min)	8/10
Decreased anal reflex	7/9
Decreased appetite	7/10
Vomiting/Regurgitation	6/9
Lethargy	7/11
Elevated third eyelid	5/11
Constipation	3/9
Dysphagia	3/9
Diarrhea	3/9
Weakness	2/9
Abdominal pain	1/10

For more information, see the the dysautonomia home page at the University of Missouri, College of Veterinary Medicine.

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