Changes

Also known as: '''''Autonomic Polyganglioneuropathy — Feline Dysautonomia

| Also known as:

| '''Autonomic Polygangioneuropathy'''<br>

'''Feline Dysautonomia'''

==Description==

==Introduction==

Key-Gaskell Syndrome refers to the clinical signs observed in cats with abnormal function of the sympathetic and parasympathetic nervous systems. It is similar to [[Grass Sickness|grass sickness]] in horses and, like this disease, it is often fatal.

Key-Gaskell Syndrome refers to the clinical signs observed in cats with abnormal function of the sympathetic and parasympathetic nervous systems. It is similar to [[Grass Sickness|grass sickness]] in horses and, like this disease, it is often fatal.

The syndrome has occurred as outbreaks<ref>Cave TA, Knottenbelt C, Mellor DJ, Nunn F, Nart P, Reid SW '''Outbreak of dysautonomia (Key-Gaskell syndrome) in a closed colony of pet cats.''' ''Vet Rec. 2003 Sep 27;153(13):387-92.''</ref> in the past in the UK, continental Europe and occasionally in the USA. It was first described by Key and Gaskell as a 'puzzling syndrome' causing pupillary dilatation in cats at the start of a major outbreak in the UK in 1982<ref>Key TJ, Gaskell CJ. '''Puzzling syndrome in cats associated with pupillary dilatation.''' ''Vet Rec. 1982 Feb 13;110(7):160.''</ref>. It is currently described only sporadically but recent reports suggest that the incidence of the disease may be increasing again.

The syndrome has occurred as outbreaks<ref>Cave TA, Knottenbelt C, Mellor DJ, Nunn F, Nart P, Reid SW '''Outbreak of dysautonomia (Key-Gaskell syndrome) in a closed colony of pet cats.''' ''Vet Rec. 2003 Sep 27;153(13):387-92.''</ref> in the past in the UK, continental Europe and occasionally in the USA. It was first described by Key and Gaskell as a 'puzzling syndrome' causing pupillary dilatation in cats at the start of a major outbreak in the UK in 1982<ref>Key TJ, Gaskell CJ. '''Puzzling syndrome in cats associated with pupillary dilatation.''' ''Vet Rec. 1982 Feb 13;110(7):160.''</ref>. It is currently described only sporadically but recent reports suggest that the incidence of the disease may be increasing again.

The cause of the dysautonomia is not known but numerous factors have been implicated and it is generally thought to occur after exposure to a toxin, possibly in dry food or vaccines. As with grass sickness, it has also been suggested that toxins produced by ''[[Clostridium botulinum]]'' may be involved in the pathogenesis of the disease and a recent study showed that cats with the disease developed significantly higher titres of IgA antibody to botulinum toxins C and D than healthy controls<ref>Nunn F, Cave TA, Knottenbelt C, Poxton IR. '''Association between Key-Gaskell syndrome and infection by Clostridium botulinum type C/D.''' ''Vet Rec. 2004 Jul 24;155(4):111-5.''</ref>.  Whatever the cause, degenerative lesions develop in the autonomic ganglia, intermedio-lateral columns of spinal grey matter and in the axons of the sympathetic neurones.

The cause of the dysautonomia is not known but numerous factors have been implicated and it is generally thought to occur after exposure to a toxin, possibly in dry food or vaccines [?reference]. As with grass sickness, it has also been suggested that toxins produced by ''[[Clostridium botulinum]]'' may be involved in the pathogenesis of the disease and a recent study showed that cats with the disease developed significantly higher titres of IgA antibody to botulinum toxins C and D than healthy controls<ref>Nunn F, Cave TA, Knottenbelt C, Poxton IR. '''Association between Key-Gaskell syndrome and infection by Clostridium botulinum type C/D.''' ''Vet Rec. 2004 Jul 24;155(4):111-5.''</ref>.  Whatever the cause, degenerative lesions develop in the autonomic ganglia, intermedio-lateral columns of spinal grey matter and in the axons of the sympathetic neurones.

==Signalment==

==Signalment==

==Diagnosis==

==Diagnosis==

===Clinical Signs===

===Clinical Signs===

The sympathetic and parasympathetic nervous systems are involved in the regulation of multiple organ systems, particularly the gastro-intestinal tract and the secretory glands. Common clinical signs therefore include:

The sympathetic and parasympathetic nervous systems are involved in the regulation of multiple organ systems, particularly the gastro-intestinal tract and the secretory glands. Common clinical signs therefore include:

*'''Anorexia''' and '''constipation''' due to intestinal ileus.

*'''Anorexia''' and '''constipation''' due to intestinal ileus.

*'''Abdominal distension''' may occur as a result of generalised paralytic ileus.

*'''Abdominal distension''' may occur as a result of generalised paralytic ileus.

*'''[[Megaoesophagus]]''' due to failure of oesophageal motility. This may cause regurgitation and secondary aspiration pneumonia.

*'''[[Megaoesophagus]]''' due to failure of oesophageal motility. This may cause regurgitation and secondary aspiration pneumonia.

*'''Depression'''

*'''Depression'''

*'''Bradycardia'''

*'''Bradycardia'''

*Decreased '''lacrimation''' and '''salivation''' due to reduced tone in the parasympathetic nerves that stimulate secretion. The xerotsomia caused by reduced production of saliva may be apparent as dry mucous membranes on clinical examination.

*Decreased '''lacrimation''' and '''salivation''' due to reduced tone in the parasympathetic nerves that stimulate secretion. The xerostomia caused by reduced production of saliva may be apparent as dry mucous membranes on clinical examination.

*'''Pupillary dilatation''' due to reduced tone of the constrictor muscle of the iris, usually controlled by the parasympathetic fibres of the short ciliary nerves.

*'''Pupillary dilatation''' due to reduced tone of the constrictor muscle of the iris, usually controlled by the parasympathetic fibres of the short ciliary nerves.

===Diagnostic Imaging===

===Diagnostic Imaging===

[[Megaoesophagus|Oesophageal dilatation]] may be observed on '''plain radiographs of the chest'''. A 'trachea stripe sign' may also be visible due to the compression of the tissue between the oesophagus and trachea.   

[[Megaoesophagus|Oesophageal dilatation]] may be observed on '''plain radiographs of the chest'''. A 'trachea stripe sign' may also be visible due to the compression of the tissue between the oesophagus and trachea.   

Oesophageal hypomotility may be evident with barium contrast study or using fluoroscopy to observe the dynamic passage of food boluses into the stomach.

Oesophageal hypomotility may be evident with barium contrast study or using fluoroscopy to observe the dynamic passage of food boluses into the stomach.

===Pharmalogical Tests===

===Pharmalogical Tests===

* Topical ocular administration of dilute pilocarpine - miosis implies a postive result. However, not all respond. Response is dependent on damage to the postganglionic parasympathetic neuron causing supersensitivity of the iris muscle

* IV or SC administration of atropine (a parasympatholytic) - lack of increase in heart rate implies a positive result

*Topical ocular administration of dilute pilocarpine should result in miosis, which implies a positive result. However, not all animals respond and the response is dependent on the degree of damage to the postganglionic parasympathetic neuron causing (denervation) supersensitivity of the iris muscle.

* ID administration of histamine - the wheal and flare response may be dampened in those with dysautonomia

*Intra-venous or subcutaneous administration of atropine (a parasympatholytic) should result in an increase in the heart rate. A failure to respond implies a positive result.

*Intra-dermal administration of histamine should result in a classical wheal and flare response but this may be dampened in those animals with dysautonomia. An absence of the wheal and flare response is therefore a positive result.

=====Pathology=====

=====Pathology=====

[[Image:Ba 250 07.jpg|thumb|Histological section of a degenerate neuron from a cat with Key-Gaskell Syndrome<br><small>Copyright Susan Rhind 2007 RVC]]</small>  

[[Image:Ba 250 07.jpg|thumb|Histological section of a degenerate neuron from a cat with Key-Gaskell Syndrome<br><small>Copyright Susan Rhind 2007 RVC]]</small>  

*Histologically there is marked reduction in the number of neurones in all autonomic ganglia in the ventral horn of all levels of spinal cord accompanied by proliferation of non-neuronal cells.

*Histologically there is marked reduction in the number of neurones in all autonomic ganglia in the ventral horn of all levels of spinal cord accompanied by proliferation of non-neuronal cells. Similar changes are found in the brainstem nuclei of the cranial nerves and features of chromatolytic degeneration may be apparent in the ganglia, spinal cord and sympathetic axons.

*Similar changes in brain stem nuclei of cranial nerves.

Chromatolytic degeneration in autonomic ganglia, spinal cord intermediate grey columns and some sympathetic axons.

==Differential Diagnosis==

==Differential Diagnosis==

There are few differentials on presentation of the many manifestations of the disease. However, early in the course of disease other causes of megaoesophagus need to be considered.

There are few differential diagnoses for this clinical presentation but, early in the course of disease, other causes of [[Megaoesophagus|megaoesophagus]] should be considered.

===Supportive===

===Supportive===

Including elevated feeding, gastrostomy tube feedings or total paranteral nutrition.

Food should be provided from an elevated bowl or via a gastrostomy tube which can be left in place for several weeks if necessary. Total parenteral nutrition may be considered but this cannot be used as a long term option for nutrition and it is associated with many adverse effects.

 

===Parasympathomimetic Drugs===

===Parasympathomimetic Drugs===

Some dogs may show minor improvement on initiation of for example, bethanechol, metoclopramide.

Some dogs may show minor improvement on initiation of therapy with '''bethanechol''' or '''metoclopramide'''.

 

==Prognosis==

==Prognosis==

Guarded to poor. Recovery rates in the cat are reported as 20-40%, however this may take 2-12 months. In the dog recovery rates are lower. Despite recovery many are also left with residual impairment including intermittent regurgitation.

The prognosis is guarded or poor. Recovery rates in the cat are reported as 20-40% but it may take 2-12 months for the patient to recover fully. In the dog, recovery rates are lower. Even after making an apparent recovery, many animals are left with residual neurological deficits including intermittent regurgitation.

==References==

==References==

[[Category:Oesophagus_-_Pathology]]

[[Category:Oesophagus_-_Pathology]]

[[Category:To_Do_-_James]]

[[Category:Intestinal Diseases - Cat]][[Category:Neurological Diseases - Cat]][[Category:Oesophageal Diseases - Cat]]

[[Category:Cat]]

[[Category:Intestinal Diseases - Dog]][[Category:Neurological Diseases - Dog]][[Category:Oesophageal Diseases - Dog]]

[[Category:Intestine_-_Functional_Obstruction]]

[[Category:Intestine_-_Functional_Obstruction]]

[[Category:To_Do_-_James]]

[[Category:Peripheral Nervous System - Pathology]]

[[Category:Dog]]

[[Category:Expert Review - Small Animal]]