Feline Dysautonomia

© Feline dysautonomia (Key-Gaskell syndrome) study group; http://www.valevets.co.uk/dysautonomia/

Feline dysautonomia (FD) is a disease of domestic cats characterised by extensive degeneration of the autonomic nervous system. This causes a variety of clinical signs characterised by regurgitation, constipation, dilated pupils that are unresponsive to light, prolapsed third eyelids, and reduced tear secretion. Clinical signs usually develop over a matter of days and less than a third of affected cats survive.

FD was first reported in the early 1900s in horses in Scotland, and not described until 1982 when Key and Gaskell reported five cats from the United Kingdom with clinical signs of autonomic nervous system dysfunction. 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. 

Cause

After over twenty years of dysautonomia in cats and dogs, and almost a century of cases reported in horses, the causes of this group of diseases remains unknown.

Pathology

Dysautonomia of domestic animals is pathologically characterised by chromatolytic degeneration of the neurones in the autonomic nervous ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems.

Clinical Symptoms

The onset of clinical signs 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. 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 lacrimal 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.

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

Definitive diagnosis currently requires histological examination of autonomic ganglia (tissue samples of nerves). 

Samples for this process can only be obtained at post-mortem after cats have died. The coeliacomesenteric ganglion may be the easiest ganglion to identify. However it often proves difficult to identify this at post-mortem resulting in a failure to confirm a suspected diagnosis. Enteric and central nervous system lesions have been reported in cats.

In order to fully evaluate a suspected case of FD you MUST note heart rate, pupillary light response, anal reflex, proprioceptive responses and perform Schirmer tear tests in both eyes. Thoracic radiography to demonstrate megaoesophagus is also strongly recommended in all cases. This should ideally be obtained with the cat unsedated as sedation itself can cause megaoesophagus. If megaoesophagus is not visible on plain radiographs a barium swallow should be performed as this significantly improves detection. In addition to megaoesophagus, thoracic radiographs may demonstrate if aspiration pneumonia has occurred. 

Ocular pharmacological tests of denervation hypersensitivity should also be performed. Other tests that may be beneficial include abdominal radiography, which may demonstrate delayed gastric emptying and distension of the urinary bladder or colon. Fluoroscopic assessment of oesophageal motility may be beneficial and may detect subclinical disease in in-contact cats. 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 caudal equina lesion could cause multiple similar caudal symptoms. In less severe grades there are multiple differential diagnosis e.g. causes of regurgitation or pupillary dilation alone.

Pharmacologic 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 ciliary muscle to parasympathetic agonists. Not all cats with FD will respond to this diagnostic test.

Barium Xrays of a normal cat (left) and a cat with dysautonomia. Note enlarged oesophagus.

Treatment

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.

Obtaining physostigmine eye drops can be problematic. Bethanecol (Myocholine, Glenwoods) 1.25 to 2.5 mg q8-12 hrs per os can promote glandular, bowel and, in particular, bladder function but should not be used with other stimulants. Therapy can result diarrhoea in some cats. It must be obtained direct from Glenwoods (01634 830535) and a special treatment authorisation may be required from the Veterinary Medicines Directorate (01932 336911 www.vmd.gov.uk).

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 (Ref 3). Cisapride is available as 10 mg tablets or 1 mg/ml suspension. 

Prognosis

Original reports described survival in less than 30% of cases (Refs 6,7). In less severely affected cats survival rates are higher (Refs 2,8). Extensive megaoesophagus and dysuria have been reported as negative prognostic signs (Ref 2). 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 (Ref 3). 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.

Epidemiology
In FD no sex or breed distribution have been identified and seasonal patterns have not been consistent (Ref 10). FD is most frequently reported in cats less than 3 years old but the age range is wide (6 weeks to 11 years) (Ref 8). In multicat households FD usually overtly affects single individuals. However, there is increasing evidence that occult subclinical disease may exist in cats (Refs 3,9). FD can also present as an outbreak affecting multiple cats within a household (Refs 3,9). If more than one cat is overtly affected they are often related. (Refs 2,3,9). It is possible that a genetic susceptibility to the condition exists.

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 consumption of wildlife and a rural environment, with access to pasture land, ponds, and cattle as risk factors (Ref 1). We are currently conducting a case-control study of cats with FD.

Injection of serum from cases of acute EGS into experimental ponies causes dysautonomia lesions in ganglia (Ref 4). 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 EGS5. One toxin produced by this serotype, BoNT/C, is uniquely neurotoxic and is detected significantly more frequently in faeces 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.