Difference between revisions of "Key-Gaskell Syndrome"

Latest revision as of 16:13, 5 January 2023

Also known as: Autonomic Polyganglioneuropathy — Feline Dysautonomia

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 in horses and, like this disease, it is often fatal.

The syndrome has occurred as outbreaks^[1] 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^[2]. 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 [?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^[3]. 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

Historically, Key-Gaskell syndrome was reported most frequently in cats but the disease has now been shown to occur in dogs^[4]^[5]^[6], particularly younger animals. There is no apparent sex predisposition but the Labrador Retriever breed may be predisposed to the development of dysautonomia.

In a recent study of 65 dogs confirmed as having dysautonomia, those raised and housed in rural environments appeared to be at greater risk (56/65 dogs) for dysautonomia than dogs from urban environments^[7].

Diagnosis

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:

Anorexia and constipation due to intestinal 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.
Depression
Bradycardia
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.

The most frequent clinical signs associated with the syndrome are depression, anorexia, constipation and regurgitation or vomiting. Incontinence (faecal and urinary) has been observed less frequently.

Diagnostic Imaging

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.

Pharmalogical Tests

Various provocative tests can be used to assess the autonomic nervous systems of animals with suspected Key-Gaskell syndrome:

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.
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

Histological section of a degenerate neuron from a cat with Key-Gaskell Syndrome
Copyright Susan Rhind 2007 RVC

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.

Differential Diagnosis

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

Treatment

Treatment may be attempted with parasympathomimteic drugs but is largely supportive.

Supportive

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

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

Prognosis

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.

Key-Gaskell Syndrome Learning Resources
Vetstream To reach the Vetstream content, please select	Canis, Felis, Lapis or Equis
Literature Search Search for recent publications via CAB Abstract (CABI log in required)	Key-Gaskell Syndrome in cats and dogs publications

References

↑ 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.
↑ Key TJ, Gaskell CJ. Puzzling syndrome in cats associated with pupillary dilatation. Vet Rec. 1982 Feb 13;110(7):160.
↑ 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.
↑ Schulze C, Schanen H, Pohlenz J. Canine dysautonomia resembling the Key-Gaskell syndrome in Germany. Vet Rec. 1997 Nov 8;141(19):496-7
↑ Wise LA, Lappin MR. A syndrome resembling feline dysautonomia (Key-Gaskell syndrome) in a dog. J Am Vet Med Assoc. 1991 Jun 15;198(12):2103-6.
↑ Rochlitz I, Bennett AM. Key-Gaskell syndrome in a bitch. Vet Rec. 1983 Jun 25;112(26):614-5.
↑ Harkin KR, Andrews GA, Nietfeld JC. Dysautonomia in dogs: 65 cases (1993-2000). J Am Vet Med Assoc. 2002 Mar 1;220(5):633-9.

Hall J.H, Wimpson J. W. and Williams D.A, (2005), Disorders of the Pharynx and Oesophagus, in BSAVA Manual of Canine and Feline Gastroenterology, 2nd Edition, British Small Animal Association, Gloucester, pp 142-143
Harkin K.R, Andrews G.A, Nietfeld J.C, (2002), Dysautonomia in dogs: 65 cases (1993–2000) J Am Vet Med Assoc, Mar 1, 220(5): pp. 633-9

Webinars

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[1] 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.

[2] Key TJ, Gaskell CJ. Puzzling syndrome in cats associated with pupillary dilatation. Vet Rec. 1982 Feb 13;110(7):160.

[3] 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.

[4] Schulze C, Schanen H, Pohlenz J. Canine dysautonomia resembling the Key-Gaskell syndrome in Germany. Vet Rec. 1997 Nov 8;141(19):496-7

[5] Wise LA, Lappin MR. A syndrome resembling feline dysautonomia (Key-Gaskell syndrome) in a dog. J Am Vet Med Assoc. 1991 Jun 15;198(12):2103-6.

[6] Rochlitz I, Bennett AM. Key-Gaskell syndrome in a bitch. Vet Rec. 1983 Jun 25;112(26):614-5.

[7] Harkin KR, Andrews GA, Nietfeld JC. Dysautonomia in dogs: 65 cases (1993-2000). J Am Vet Med Assoc. 2002 Mar 1;220(5):633-9.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

@@ Line 1: / Line 1: @@
-*Autonomic polyganglioneuropathy in cats
-*Abnormal function of the sympathetic and parasympathetic system.
-*Whole autonomic system involved – affected animals usually die.
-**Similar to [[Grass Sickness|grass sickness]] in horses.
-=====Clinical=====
+Also known as: '''''Autonomic Polyganglioneuropathy — Feline Dysautonomia
-*Cats show:
-**[[Megaoesophagus]]
-**Dilated pupils
-**Whole gut is involved (very little peristalsis)
-**Constipation.
-*Generalised autonomic effects:
+==Introduction==
-**Reduced salivation
+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.
-**Reduced lachrymation
-**Bradycardia
-**Constipation
-**Pupillary dilatation
-=====Pathology=====
-*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 in brain stem nuclei of cranial nerves.
-=====Pathogenesis=====
-*Acquired disease - outbreaks occurred in the past, now only occasionally seen but seems to be getting more common again.
-*Possibly toxic cause.
-*Possibly in dry food or in vaccine?
-*Agent not really known, but produces general damage to autonomic nervous system.
+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.
-=====Feline dysautonomia, or Key-Gaskell Syndrome=====
+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.
-[[Image:Ba 250 07.jpg|thumb|right|Histological section of degenerate neuron in feline dysautonomia(Courtesy of Susan Rhind)]]
-* Occurs mostly in the UK and continental Europe.
-* Is also of unknown aetiology. Suggested causative factors include:
-** Environmental toxins
-** Infectious agents
-** Botulinum toxins .
-* Clinical signs:
-** Anorexia
-** Depression
-** Bradycardia
-** Decreased lacrimation,
-** Altered pupillary dilataion,
-** [[Megaoesophagus]]
-** Constipation.
-* Degenerative lesions of autonomic nerve ganglia can be seen.
-* Also occurs in the [[Key-Gaskell Syndrome|oesophagus]].
-Also known as Feline Key-Gaskell Syndrome and Feline Autonomic Polygangliopathy.
-Part of a syndrome of generalised autonomic neuropathy. It has been observed throughout Western Europe and The United States.
 ==Signalment==
-* Historically reported  most frequently in cats but now also in dogs
+Historically, Key-Gaskell syndrome was reported most frequently in cats but the disease has now been shown to occur in dogs<ref>Schulze C, Schanen H, Pohlenz J. '''Canine dysautonomia resembling the Key-Gaskell syndrome in Germany.''' ''Vet Rec. 1997 Nov 8;141(19):496-7''</ref><ref>Wise LA, Lappin MR. '''A syndrome resembling feline dysautonomia (Key-Gaskell syndrome) in a dog.''' ''J Am Vet Med Assoc. 1991 Jun 15;198(12):2103-6.''</ref><ref>Rochlitz I, Bennett AM. '''Key-Gaskell syndrome in a bitch.''' ''Vet Rec. 1983 Jun 25;112(26):614-5. ''</ref>, particularly younger animals. There is no apparent sex predisposition but the Labrador Retriever breed may be predisposed to the development of dysautonomia.
-* Usually seen in younger dogs
-* No sex predisposition
-* In a recent study of 65 dogs confirmed as having dysautonomia those raised and housed in rural environments appeared to be at greater risk (56/65 dogs) for dysautonomia than dogs from the city
-* Labrador Retrievers may have a breed predisposition
-==Description==
+In a recent study of 65 dogs confirmed as having dysautonomia, those raised and housed in rural environments appeared to be at greater risk (56/65 dogs) for dysautonomia than dogs from urban environments<ref>Harkin KR, Andrews GA, Nietfeld JC. '''Dysautonomia in dogs: 65 cases (1993-2000).''' ''J Am Vet Med Assoc. 2002 Mar 1;220(5):633-9.''</ref>.
-* Degenerative lesions of the autonomic ganglia, spinal cord intermediate grey columns and sympathetic axons
-* Aetiology still largely idiopathic
 ==Diagnosis==
 ===Clinical Signs===
-Those of a generalised autonomic dysfuntion of the gastrointestinal and urinary tracts. Those associated with the oesophagus 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:
-* Regurgitation
+*'''Anorexia''' and '''constipation''' due to intestinal ileus.
-* Megaoesophagus
+*'''Abdominal distension''' may occur as a result of generalised paralytic ileus.
-* Oesophageal hypotmotility
+*'''[[Megaoesophagus]]''' due to failure of oesophageal motility. This may cause regurgitation and secondary aspiration pneumonia.
+*'''Depression'''
+*'''Bradycardia'''
+*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.
 The most frequent clinical signs associated with the syndrome are depression, anorexia, constipation and regurgitation or vomiting. Incontinence (faecal and urinary) has been observed less frequently.
-===Physical Examination===
+===Diagnostic Imaging===
-Findings associated with the GI system include:
+[[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.
-* Dry mucous membranes
-* Intestinal distension
-===Radiography===
+Oesophageal hypomotility may be evident with barium contrast study or using fluoroscopy to observe the dynamic passage of food boluses into the stomach.
-====Plain Radiography====
-Oesophageal dilatation may be observed.
-====Contrast Radiography====
-Oesophageal hypomotility may be evident on barium contrast study.
-===Histological Findings===
+===Pharmalogical Tests===
-Chromatolytic degeneration in autonomic ganglia, spinal cord intermediate grey columns and some sympathetic axons.
+Various provocative tests can be used to assess the autonomic nervous systems of animals with suspected Key-Gaskell syndrome:
+*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.
+*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.
-===Pharmalogical Testing===
+=====Pathology=====
-* 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
+[[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>
-* IV or SC administration of atropine (a parasympatholytic) - lack of increase in heart rate implies a positive result
+*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.
-* ID administration of histamine - the wheal and flare response may be dampened in those with dysautonomia
 ==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.
+==Treatment==
+Treatment may be attempted with parasympathomimteic drugs but is largely supportive.
-==Treatment==
 ===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===
-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==
-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.
+{{Learning
+|Vetstream = [https://www.vetstream.com/canis/Content/Disease/dis60161.asp, Canine dysautonomia]<br>[https://www.vetstream.com/felis/Content/Disease/dis60161.asp, Feline dysautonomia]
+|literature search = [http://www.cabdirect.org/search.html?q=%28title%3A%28%22Key+Gaskell%22%29+OR+title%3A%28dysatonomia%29+OR+title%3A%28%22Autonomic+Polyganglioneuropathy%22%29%29+AND+%28od%3A%28cats%29+OR+od%3A%28dogs%29%29 Key-Gaskell Syndrome in cats and dogs publications]
+}}
 ==References==
+<references/>
 * Hall J.H, Wimpson J. W. and Williams D.A, (2005), Disorders of the Pharynx and Oesophagus, in BSAVA Manual of Canine and Feline Gastroenterology, 2nd Edition, British Small Animal Association, Gloucester, pp 142-143
 * Harkin K.R, Andrews G.A, Nietfeld J.C, (2002), Dysautonomia in dogs: 65 cases (1993–2000) J Am Vet Med Assoc, Mar 1, 220(5): pp. 633-9
+{{review}}
+==Webinars==
+<rss max="10" highlight="none">https://www.thewebinarvet.com/neurology/webinars/feed</rss>
+[[Category:Oesophagus_-_Pathology]]
-[[Category:Cat]]
+[[Category:Intestinal Diseases - Cat]][[Category:Neurological Diseases - Cat]][[Category:Oesophageal Diseases - Cat]]
+[[Category:Intestinal Diseases - Dog]][[Category:Neurological Diseases - Dog]][[Category:Oesophageal Diseases - Dog]]
 [[Category:Intestine_-_Functional_Obstruction]]
+[[Category:Peripheral Nervous System - Pathology]]
-[[Category:To_Do_-_James]]
+[[Category:Expert Review - Small Animal]]