Dysautonomia in a Flat-Coated Retriever

Adam Gow BVM&S CertSAM MRCVS

HILL’S SENIOR CLINICAL SCHOLAR IN INTERNAL MEDICINE
ROYAL (DICK) SCHOOL OF VETERINARY STUDIES, UNIVERSITY OF EDINBURGH, HOSPITAL FOR SMALL
ANIMALS, EASTER BUSH VETERINARY CENTRE, ROSLIN, EDINBURGH. EH25 9RG

CASE HISTORY INITIAL INVESTIGATION

A 1-year-old, entire male Flat-Coated Retriever was Blood tests
referred with a six-day history of acute onset vomiting. Routine haematology and serum biochemistry
Vomiting had started 24 hours after scavenging a were unremarkable. Cortisol levels post-ACTH
carcass whilst out on a walk. Supportive treatment with stimulation were consistent with a normal
intravenous fluids and metoclopramide had produced response.
only a temporary improvement. Some diarrhoea had
been noted initially although this had resolved and Radiography
no faeces had been passed for four days. On day six, Radiographs of thorax and abdomen were
a high gastrointestinal obstruction was suspected by performed. Thoracic films were unremarkable.
the referring veterinary surgeon, based on clinical Abdominal films are shown in Figs. 1 and 2. A large
signs, electrolyte imbalances and blood pH. An amount of free abdominal gas was present,
exploratory coeliotomy was performed but no
obvious obstruction was identified, although the
stomach appeared distended and fluid filled. Gastric
fluid had been removed via stomach tube. The case
recovered from general anaesthesia and was referred
at this point. Apart from this illness, the dog had no
other relevant clinical history.

CLINICAL PRESENTATION
On presentation, the dog appeared dull and
depressed, possibly due to general anaesthesia. Clear
fluid was vomited multiple times during the
consultation. Mucous membranes were tacky,
capillary refill time was approximately two seconds
and peripheral pulses were weak. Dehydration was
estimated at 7-8%. Heart rate was 120 beats per
minute with a matched pulse. Rectal temperature was
37°C. Abdominal palpation revealed only generalised Fig. 1: Lateral abdominal radiograph. Note the large amount of free abdominal
discomfort, thought to be due to the coeliotomy. gas and mineral opacities in small intestine and colon.

Although the prior general anaesthesia and surgery

were contributing to the clinical picture, the main
problems were: vomiting, hypovolaemia, possible
relative bradycardia, abdominal discomfort and
hypothermia. As these signs were compatible with
hypoadrenocorticism, an ACTH stimulation test as
well as base-line haematology and serum
biochemistry was performed.

INITIAL TREATMENT
Initial management was directed at addressing
hypovolaemia and hypothermia.Warmed Hartmann’s
solution was administered intravenously at 60 ml/kg/hr
initially. A warm-air blanket was used to improve
body temperature.These measures (and likely further
time to recover from general anaesthesia) improved
the dog’s demeanour and cardiovascular status. Fig. 2: Ventrodorsal abdominal radiograph.

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 hampering interpretation. Some small mineralised Subsequently the dog also became progressively
opacities (thought to be bone fragments) are present dysuric and overflow incontinence occurred, yet the
in the small intestine and colon. bladder could easily be expressed manually. Faecal
tenesmus also developed (Fig. 5) and the dog became
Endoscopy progressively dysphagic.
At this point, as a gastrointestinal obstruction could
not be ruled out, gastro-duodenoscopy was
performed. Mild oesophagitis was present in the
lower oesophagus. A large volume of fluid was
present in the gastric lumen. Entry to the pylorus
and a distance into the duodenum was unimpeded,
which ruled out a high obstruction and made a
functional disease the likely cause of delayed gastric
emptying. Biopsies were obtained from both the
duodenal and gastric mucosa.

Treatment with sucralfate and ranitidine was given,

as oesophageal and gastro-protection. Analgesia for
the laparotomy wound and oesophagitis was
provided initially with pethidine and then
buprenorphine. Intravenous fluids were reduced to
maintenance requirements once hypovolaemia had
been reversed and metoclopramide was added as a Fig. 4: No further transit of gastric spheres 48 hours after administration.
continuous rate infusion to stimulate gastrointestinal
motility and reduce vomiting. Barium-impregnated
polyethylene spheres (BIPS) were administered
orally to further assess gastrointestinal motility and
rule out any more distal obstruction.

FURTHER INVESTIGATION AND SIGNS

Over the next 48 hours further signs became
evident. Despite adequate fluid replacement, mucous
membranes remained tacky. Blepharospasm was seen
in bright light and pupillary constriction failed to
occur. The third eyelids appeared prolapsed.
Radiography was repeated to assess movement of
BIPS 24 hours after administration (Fig. 3). Two
small spheres are visible in the descending colon,
however the majority of the BIPS remained in the
pylorus. Prior endoscopy had ruled out a physical
obstruction in this area. Radiography was repeated Fig. 5: Tenesmus developed with small quantities of diarrhoea being passed.
48 hours after BIPS administration (Fig. 4). No
further movement of the spheres was seen. At this point, canine dysautonomia was thought to
be a possible diagnosis. Canine dysautonomia is
characterised by a failure of the autonomic nervous
system and clinical signs relate to reduced or absent
sympathetic and/or parasympathetic control, and
typically carries a grave prognosis. Further testing
to increase confidence in the diagnosis of
dysautonomia was carried out.

A Schirmer tear test revealed 0 mm tear production

Fig. 3: Abdominal radiograph 24 hours after BIPS administration. Two small
spheres are in the colon; however the vast majority remain in the gastric lumen.
in the right eye and 9 mm in the left (reference
range >15 mm/min). Lacrimation is under
parasympathetic control and a reduction may be due
either to a problem at this level or destruction of the
lacrimal gland (e.g. immune-mediated destruction
seen in keratoconjunctivitis sicca). Ocular
examination revealed the pupils to be in the mid-
range and unresponsive to light (Fig. 6).Vision was
unaffected. This was consistent with loss of
parasympathetic innervation to the iris. One drop of

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 0.05% pilocarpine was administered to the left eye possibly due to a loss of parasympathetic control.The
and this was monitored for evidence of pupillary proposed scoring scheme for dysautonomia was used
constriction. The contralateral eye was used as a (Table 1) and this supported the diagnosis.
control. Miosis occurred within 20 minutes (Fig. 7).
Unaffected dogs either do not respond to such a low
concentration of pilocarpine, or the response takes
45-60 minutes. This rapid response would suggest
denervation sensitivity.

Fig. 8: Histamine injected into suspect dysautonomic on left. Normal control

result on right showing weal and flare reaction. (Control photo courtesy of
Carla Deloda, University of Edinburgh.)

Fig. 6: Even in bright light, pupils remained in the mid

range and the dog was photophobic.

Fig. 7: Comparison of eyes in the same light intensity 20 minutes after

administering dilute pilocarpine to the left eye (left side on photo).

Apart from the ocular findings, the only other

abnormalities detected on routine neurological
examination were a reduced gag reflex and lack of Fig. 9: Dry nasal mucosa with dry discharge visible.
anal tone. These abnormalities have been reported

TABLE 1: Proposed scoring system for dysautonomia

previously in canine dysautonomia and are

(Jamieson et al., 2002)

intriguing, as neither is under autonomic control.

Heart rate had remained within the narrow range of Clinical sign Score Case score
80-100 beats per minute for much of the time. An
Bladder atony or dysuria 3 3
atropine response test abolishes parasympathetic
(vagal) control of heart rate. In most dogs this results Dilated pupils/reduced PLR 3 3
in an increase in heart rate due to sympathetic drive. Decreased tear production 3 3
In cases of dysautonomia, no significant change in Dry nasal mucus 3 3
rate would be expected as both sympathetic and Dilated, areflexic anal sphincter 3 3
parasympathetic control has been removed. Regurgitation/reduced oesophageal motility 3 0
Intravenous atropine at a dose of 0.02 mg/kg in this
Third eyelid prolapse 2 2
case failed to produce an increase in rate during the
60 minutes the rate was monitored, even when the Intestinal hypomotility 2 2
dog was exercised. Dysphagia 2 2
Syncope 2 0
It has been suggested that failure of sympathetic Vomiting 1 1
supply to intradermal blood vessels will prevent a Diarrhoea 1 1
normal reaction to intradermal injection with
Constipation/tenesmus 1 1
histamine. In this case, no weal or flare reaction
occurred (Fig. 8). Over the course of hospitalisation, Abdominal pain 1 0
the nasal mucosa became progressively more crusted Total 30 24
and dry (Fig. 9), suggesting a lack of secretion, Score: 0-10 - inconclusive (monitor and reassess); 11-20 - probable; 21-30 - positive

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 Supportive treatment was discussed with the owners,
however they elected to have the dog euthanased.
Post-mortem examination was allowed. Gross post-
mortem examination confirmed the evidence of
oesophagitis, likely due to vomiting. Histopathology
of the thoracic stellate ganglia showed reduced
numbers of neurones with chromatolysis. Neurones
in the duodenal submucosa and myenteric plexus
appeared reduced, with many appearing shrunken,
with eosinophilic cytoplasm. Similar chromatolysis
and reduction in numbers of neurones were seen in
the bladder wall. These histopathological findings
were consistent with the diagnosis of dysautonomia.
DISCUSSION
Primary dysautonomia describes degeneration of
neurones in the autonomic ganglia. The syndrome
has long been recognised in horses. It was first
described in UK cats in the 1980s, and is commonly
known as Key-Gaskell syndrome in this species.This
feline form became extremely common during the
1980s and was reported worldwide before the
incidence declined dramatically. Dysautonomia has
also been reported in hares, rabbits and a llama as
well as in dogs.
Canine dysautonomia appears to be most common
in the USA, with an apparent hot-spot in the
Midwest.At present, only ten canine cases have been
reported in the UK. All UK cases were euthanased
due to the severity of the clinical signs and poor
response to symptomatic treatment. Although many
cases have been described worldwide, the cause has
remained elusive. Risk factors for dogs identified in
one retrospective study were living in a rural
environment, eating wildlife and spending >50% of
their time outdoors.
In humans with the similar disease, subacute
idiopathic autonomic neuropathy, antibodies against
ganglionic acetylcholine receptors have been
identified, suggesting a possible immune-mediated
cause. These antibodies have been demonstrated in
some canine cases of dysautonomia. Clostridium
botulinum types C/D, which produce neurotoxins,
have been identified as a potential cause in horses.
This toxin has been identified in seven out of eight
cats affected in one outbreak and also in samples of
their dried food. At present, there are no reports of
affected dogs being tested for this possible cause.
Failure of the parasympathetic system causes the
most obvious clinical signs.The constellation of signs
includes:
l weight loss
l vomiting
l regurgitation
l diarrhoea or constipation
dysuria
l
l photophobia (due to failure of pupillary
constriction)
l keratoconjunctivitis sicca
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The presentation is typically acute and in many cases
(this one included), the initial clinical sign is one of
gastrointestinal dysfunction. As the majority of cases
occur in young dogs (median age of 14 months in
one study), a gastrointestinal obstruction is often
suspected. Regurgitation due to megaoesophagus is
also common (although this was not identified in
this case) and therefore a common complication is
aspiration pneumonia. A barium swallow could have
been performed to further assess oesophageal motility,
however this was not deemed necessary and would
have carried with it the risk of barium aspiration.
Loss of sympathetic tone causes less dramatic clinical
signs. The fact that the pupils were mid-range,
suggests that there was loss of sympathetic control,
which would allow pupillary dilation. The rapid
response seen to dilute pilocarpine is due to
sensitivity caused by post-ganglionic denervation of
the parasympathetic supply to the iris.
Loss of parasympathetic stimulation prevents detrusor
muscle contraction. Coupled with a lack of urethral
tone, this results in a full bladder that is easily expressible
(i.e. lower motor neurone signs to the bladder).
Management of chronic cases
Although most cases present acutely, some have been
described with a chronic presentation over a number
of years. As the cause of neuronal degeneration has
not been identified, treatment is purely symptomatic.
The body systems which generally require
management are gastrointestinal, urinary and ocular.
Gastrointestinal signs
If megaoesophagus or reduced oesophageal motility
are present then feeding in a vertical position and
encouraging the animal to remain vertical for a time
after feeding is useful.The type of diet (wet/dry) that
is best tolerated appears to depend on the individual.
Prokinetics to improve gastric and intestinal motility
may be used. Many of these drugs act on the myenteric
plexus, and, as a result, their efficacy may be poor. In
the cases reported, metoclopramide appears to have
been used most commonly.This is a cholinomimetic,
acting on muscarinic receptors of smooth muscle. One
potential problem is that lower oesophageal sphincter
tone may be increased with this drug, making
megaoesophagus management more difficult.
Urinary tract and ocular signs
Bethanechol chloride (Myotonine) is a muscarinic
agonist. It increases detrusor muscle tone and may
improve the animal’s ability to urinate. An
improvement in ocular signs (lacrimation, pupillary
response to light), salivation and appetite may be
seen. Pilocarpine drops may also be used to improve
ocular signs; again this is a parasympathomimetic.
PROGNOSIS
The prognosis for canine dysautonomia is grave. Of
the reported cases reviewed, over 90% (85 of 92)
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 CONTINUING PROFESSIONAL
have either died or been euthanased due to the
severity of clinical signs or complications such as DEVELOPMENT SPONSORED BY
aspiration pneumonia. Cases which appear to have C E VA A N I M A L H E A LT H
responded to medical management have had limited These multiple choice questions are based on the above
clinical signs (e.g. dysuria only) or a slowly text. Answers appear on page 99.
progressive form of the disease. 1. What age range of dog is most commonly affected
with dysautonomia:
This case highlights the point that, although a. Young dogs
uncommon, canine dysautonomia should be b. Middle-aged dogs
considered as a differential in any vomiting/ c. Old dogs
regurgitating dog. Other signs of autonomic d. No age predisposition

2. Stimulation of the sympathetic nervous system

dysfunction may develop subsequently or require
causes increased lacrimation:
diligent investigation to confirm their presence.
True or False?
FURTHER READING
ADAMAMA-MORAITOU, K. K., BRELLOU, G. D., RALLIS, T. S., 3. In dysautonomic dogs, the most common
ZAVROS, N., PARDALI, D., DINOPOULOS, A. and VLEMMAS, I. differential diagnosis suspected is:
(2006) Chronic progressive autonomic dysfunction in a dog. Journal of a. Myasthenia gravis
Veterinary Medicine Series A: Physiology, Pathology, Clinical Medicine b. Gastrointestinal obstruction
53, 81-4. c. Hypoadrenocorticism
BERGHAUS, R. D., O’BRIEN, D. P., JOHNSON, G. C. and THORNE, J. d. Keratoconjunctivitis sicca

4. Medical treatment of dysautonomia may include:

G. (2001) Risk factors for development of dysautonomia in dogs. Journal
of the American Veterinary Medical Association 218, 1285-90.
a. Pyridostigmine
BERGHAUS, R. D., O’BRIEN, D. P., THORNE, J. G. and BUENING, G.
b. Bethanechol
M. (2002) Incidence of canine dysautonomia in Missouri, USA, between
c. Atropine
January 1996 and December 2000. Preventive Veterinary Medicine 54,
d. Maropitant
291-300.
DETWEILER, D. A., BILLER, D. S., HOSKINSON, J. J. and HARKIN, K.
R. (2001) Radiographic findings of canine dysautonomia in twenty-four
dogs. Veterinary Radiology and Ultrasound 42, 108-112.
HARKIN, K. R., ANDREWS, G. A. and NIETFELD, J. C. (2002)
Dysautonomia in dogs: 65 cases (1993-2000). Journal of the American
Veterinary Medical Association 220, 633-9.
HARKIN, K. R., NIETFELD, J. and FISCHER, J.R. (2002) Dysautonomia
in a family of German shorthaired pointers. Journal of the American
Animal Hospital Association 38, 55-9.
JAMIESON, P. M., SCUDAMORE, C. L., RUPPERT, C. E., MAUCHLINE,
S. and SIMPSON, J. W. (2002) Canine dysautonomia: two clinical cases.
Journal of Small Animal Practice 43, 22-6.
LONGSHORE, R. C., O’BRIEN, D. P., JOHNSON, G. C., GROOTERS,
A. M. and KROLL, R. A. (1996) Dysautonomia in dogs: a retrospective
study. Journal of Veterinary Internal Medicine 10, 103-109.
NIESSEN, S. J., EASTWOOD, J., SMYTH, J. B. and CHERUBINI, G. B.
(2007) Five cases of canine dysautonomia in England (2004 to 2006).
Journal of Small Animal Practice 48, 346-52.
O’BRIEN, D. P. and JOHNSON, G. C. (2002) Dysautonomia and
autonomic neuropathies. Veterinary Clinics of North America: Small
Animal Practice 32, 251-65, viii.

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