Dysautonomia

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Sequential radiographs showing a barium-meal swallow passing along the oesophagus in a cat with dysautonomia. Note the enlarged diameter of the oesophagus
Barium radiographs of a normal cat (left) and a cat with dysautonomia. Note enlarged oesophagus.
Dysautonomia2.jpg
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Histological section of degenerate neuron in feline dysautonomia

Feline dysautonomia (FD) or Key-Gaskell syndrome, is a neurological disease of cats characterized by failure of the autonomic nervous system due to autonomic ganglia degeneration[1].

Clinical signs are related to dysfunction of the sympathetic and parasympathetic nervous systems. The cause is unclear, although association with Clostridium botulinum neurotoxin has been described in horses and cats[2].

Epidemiology

Dysautonomia was first reported in the early 1900s in horses in Scotland, and not described in cats until 1982 when Key and Gaskell reported five cats from the United Kingdom with clinical signs of autonomic nervous system dysfunction[3]. Since the 1980s, dysautonomia has been reported worldwide in horses, cats, dogs, hares and a llama. It doesn't appear to have been diagnosed in Australia as yet. With the exception of canine dysautonomia, which has largely been reported from the mid-western USA, the vast majority of animals with dysautonomia have been reported in Britain[4].

In FD no sex or breed distribution have been identified and seasonal patterns have not been consistent. FD is most frequently reported in cats less than 3 years old but the age range is wide (6 weeks to 11 years). In multicat households FD usually overtly affects single individuals. However, there is increasing evidence that occult subclinical disease may exist in cats. FD can also present as an outbreak affecting multiple cats within a household. If more than one cat is overtly affected they are often related. It is possible that a genetic susceptibility to the condition exists[5].

To date uncontrolled epidemiological studies have not reported a common environmental or management factor in cats or been supportive of direct contagion. The similarities between FD and dysautonomias of other species suggest that a comparative approach may be beneficial. A case-control study of canine dysautonomia identified as risk factors consumption of wildlife and a rural environment, with access to pasture land, ponds, and cattle .

Injection of serum from cases of acute EGS into experimental ponies causes dysautonomia lesions in ganglia. The toxic serum component is greater than 30 kDa in size and appears to undergo retrograde axonal transport. A toxicoinfection by Clostridium botulinum serotype C has been proposed as the cause of EGS. One toxin produced by this serotype, BoNT/C, is uniquely neurotoxic and is detected significantly more frequently in feces from horses with EGS than normal animals. In normal cats BoNT/C has not been detected in faeces. FD cats tested to date have all had measurable BoNT/C in faeces (unpublished data). Further work is required to fully identify the role of BoNT/C in FD.

Dysautonomia is pathologically characterised by chromatolytic degeneration of the neurones in the autonomic nervous system ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems. Similar degeneration occurs less commonly in the CNS.

Clinical Signs

The onset of clinical signs in cats varies from a few hours to several weeks. Prodromal signs (serous oculo-nasal discharge or diarrhoea) have been reported. Some common clinical signs such as constipation, prolapsed third eyelids, and dry mouth are very non-specific i.e. they are also seen in many other diseases. Others such as reduced tear secretion, mydriasis (dilated pupils), anisocoria (different sized pupils) with bilateral prolapsed nictitans, regurgitation, bradycardia and megaoesophagus are more specific to FD in cats[6].

Dysautonomia is characterised by regurgitation, constipation, ophthalmological disorders such as dilated pupils that are unresponsive to light, prolapsed third eyelids, and reduced tear secretion.

It is generally the finding of multiple clinical signs in the same cat that suggest a diagnosis of FD. Dilated pupils, prolapsed third eyelids, reduced lacimal secretions, regurgitation, and constipation were seen in over 75% of pre-1984 cases. Each of these signs occurred in less than 60% of cases between 1984 and 1987 suggesting that the clinical severity of FD may have reduced. This trend has not been supported by more recently reported cases[7].

While the disease is typically seen in cats less than 3 years of age, it has been recorded in felines between 2 months of age and 11 years old. Clinical signs develop in less than 48 hrs in most cases and prognosis is poor with a reported 70% mortality rate. Dysautonomia typically occurs in cats with routine access to the outdoors. and an indoor lifestyle might suggest lower risk for developing the disease

Diagnosis

The diagnosis is suspected on clinical signs. Response to ocular instillation of pilocarpine drops (0.05 - 0.1%) and subcutaneous injections of bethanacol chloride have been used to rule out the inability of the iris and detrusor muscles to contract and thus suggest denervation hypersensitivity, which would indicate a postganglionic lesion[8].

Definitive diagnosis currently requires histological examination of autonomic ganglia (tissue samples of nerves). The coeliacomesenteric ganglion may be the easiest ganglion to identify. However it often proves difficult to identify this, resulting in a failure to confirm a suspected diagnosis.

Enteric and central nervous system lesions have been reported in cats[9].

Thoracic radiography to demonstrate megaoesophagus is also strongly recommended in all cases. Additional tests employed in past cases include detection of reduced plasma or urine catecholamine levels or response to intradermal histamine. Routine haematology, serum biochemistry, and virology are only useful in identifying concurrent conditions.

Differential diagnoses are few in cats with multiple cardinal clinical signs. A cauda equina lesion could cause similar bladder, rectal and anal signs. In less severe grades, there are multiple differential diagnosis e.g. causes of regurgitation or pupillary dilation alone.

Pharmacological agents used for testing autonomic function in cats with FD include the administration of dilute pilocarpine ophthalmic solution, subcutaneous injections of atropine and intradermal administration of histamine. Miosis after administration of pilocarpine is consistent with dysautonomia and reflects denervation-induced hypersensitivity of the iris constrictor muscle to parasympathetic agonists. Not all cats with FD will respond to this diagnostic test.

Treatment

Less than a third of affected cats survive[10].

Severely affected cats may require correction of dehydration and electrolyte disturbances with intravenous fluid therapy. Oxygen therapy may be necessary if severe concurrent aspiration pneumonia is present. Normothermia should be maintained through provision of a heat source if necessary. Liquid paraffin enemas may relieve constipation. Manual bladder emptying should be performed if the bladder is atonic. Respiratory and urinary infections should be treated aggressively with antibiotics. Regurgitation should be prevented by aspiration of oesophageal contents via a naso-oesophageal tube. Oral intake of food and water may be contraindicated if oesophageal dysfunction is severe. Total and partial parenteral nutrition can provide short-term nutritional support but gastrotomy tubes can be beneficial for long-term patients. Less severely affected cats are aided by postural feeding. Great care is required if severe aspiration and dyspnoea are present as even minimum diagnostic or therapeutic intervention can result in respiratory arrest and death.

  • Autonomic stimulants such as pilocarpine 0.1-0.5% or physostigmine 0.5% eye drops may aid oronasal and lacrimal secretion but can induce side effects such as abdominal cramps and muscle fasciculations.
  • Danthron, although reported to be beneficial, has been shown to be carcinogenic and so requires caution if dispensed to owners. All in contact with the drug should wear gloves.
  • Metoclopramide 0.5 to1.0 mg/kg q8 hrs per os, subcutaneously, or intravenously has been shown to improve gastric emptying in FD but not oesophageal motility (Ref 8).
  • Cisapride (Prepulsid, Janssen-Cilag) has been reported to improve gastrointestinal transit time in horses with dysautonomia. We have failed to detect fluoroscopic improvement in oesophageal motility in FD cats treated with cisapride 1 mg/kg q8 hrs per os but noted increased rates of regurgitation when it was withdrawn for 7 days during chronic management. Cisapride is available as 10 mg tablets or 1 mg/ml suspension.

Original reports described survival in less than 30% of cases. In less severely affected cats survival rates are higher. Extensive megaoesophagus and dysuria have been reported as negative prognostic signs. We found evidence that sequential heart rate measurement may be a prognostic indicator.

Heart rates in surviving cats were higher and had more inter-measurement variation than in non-survivors. Further evaluation in larger groups is required. In survivors, dilated pupils and megaoesophagus appear persistent but cats usually regurgitate less frequently.

Constipation may be recurrent and cats may fail to gain weight. Some surviving cats appear to undergo acute deteriorations later in life. Faecal incontinence or a sudden deterioration in clinical grade may develop as a late complication.

References

  1. Novellas, R et al (2010) Imaging findings in 11 cats with feline dysautonomia. JFMS 12:584-591
  2. Nunn, F et al (2004) Association between Key-Gaskell syndrome and infection by Clostridium botulinum type C/D. Vet Rec 155:111-115
  3. Key TJA, Gaskell CJ. (1982) Puzzling syndrome in cats associated with pupillary dilatation. Vet Rec 110(7):160
  4. Kidder AC, Johannes C, O'Brien D, et al (2008) Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases. J Feline Med Surg 10(2):130-136
  5. O'Brien DP, Johnson GC. (2002) Dysautonomia and autonomic neuropathies. Vet Clin North Am Small Anim Pract 32(1):251-265
  6. Lyons WR (1998) Key-Gaskell syndrome in cats. Vet Rec 143(20):568
  7. Cave TA, Knottenbelt C, Mellor DJ, et al (2001) Feline dysautonomia in a closed colony of pet cats. Vet Rec 149(25):779
  8. Coates, JR (2004) Tail, anal, and bladder dysfunction. In: Platt, SR & Olby NJ (Eds). BSAVA manual of canine and feline neurology. 3rd edition. British Small Animal Veterinary Association, Glouchester, pp:302-319
  9. Guilford WG, O'Brien DP, Allert A, Ermeling HM. (1988) Diagnosis of dysautonomia in a cat by autonomic nervous system function testing. JAVMA 193(7):823-828
  10. Kidder, AC et al (2008) Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases. JFMS 10:130-136