Clinical equine dysautonomia and autonomic neuron damage.

Damage to the neurons of selected autonomic ganglia was quantified in relation to the severity of the clinical signs shown in acute, subacute and chronic cases of dysautonomia (grass sickness). No connection between the clinical severity of acute or subacute dysautonomia and the amount of neuronal damage in the superior cervical, stellate and coeliaco-mesenteric ganglia could be demonstrated. However, a higher proportion of normal neurons were found in chronic cases. Jejunal submucosal neuronal damage was correlated with clinical severity but further work is required to confirm this finding and to establish how widespread the alimentary neuronal lesions are in dysautonomia of different severities.     

Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases

Dysautonomia of domestic animals is pathologically characterized by chromatolytic degeneration of the neurons in the autonomic nervous ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems. The exact cause is unknown. It has a poor prognosis among all species reported and no definitive treatment is available currently. To date, most reported feline cases have occurred in the United Kingdom and Scandinavia. The cases reported here highlight the clinical signs, physical examination findings, and results of autonomic nervous system function testing in nine cats with dysautonomia in the US. Feline dysautonomia is uncommon in the US, but may have a regional prevalence, as is seen in dogs with most cases reported in Missouri and Kansas.     

Dysautonomia in dogs: 65 cases (1993-2000)

OBJECTIVE: To determine signalment, history, clinical findings, results of autonomic function testing and other antemortem diagnostic tests, and pathologic findings in dogs with dysautonomia. DESIGN: Retrospective study. ANIMALS: 65 dogs with dysautonomia. PROCEDURE: Case records of 68 dogs with a diagnosis of dysautonomia were reviewed; inclusion criteria included histologic confirmation of dysautonomia or clinical signs and results of pharmacologic testing consistent with dysautonomia. RESULTS: 65 dogs fulfilled all criteria for dysautonomia. Dogs from rural environments were overrepresented, and cases of dysautonomia were reported for every month, although the highest number of cases was reported in February and March. Vomiting was the most common clinical sign, followed by diarrhea, signs of anorexia and depression, weight loss, and dysuria. The most common physical examination finding was decreased or absent anal tone, followed by absent pupillary light reflexes and elevated nictitating membrane. Results of pharmacologic testing were consistent with dysautonomia, although no single test was 100% sensitive. Histologic lesions consistent with dysautonomia were found in the autonomic ganglia, brainstem nuclei, and ventral horns of the spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE: Dysautonomia is an endemic disease in Kansas, and a high index of suspicion of the disease can be made by combining clinical signs, physical examination findings, and results of pharmacologic testing.     

Key-Gaskell syndrome in a cat in Switzerland

As far as the authors know this is the first case of Key-Gaskell-syndrome being described in Switzerland. The clinical signs of megaoesophagus, anorexia, constipation, dryness of all mucous membranes, reduced tear production, protrusion of the membrana nictitans, mydriasis, regurgitation and bradycardia are pathognomonic and can't be mistaken by any other disease. The subject of the Key-Gaskell-syndrome is a dysfunction of the autonomic nervous system. Histopathological changes are exclusively related to the autonomic nervous system and to neurons of some nuclei in the cranial nerves. Less severe changes can be found in the neurons of the spinal cord or in the dorsal root ganglia. The etiology remains still unclear. There is a relationship to the grass sickness syndrome in horses and to dysautonomia of man and dog.     

Small intestine and small colon neuropathy in equine dysautonomia (grass sickness)

The number of neurons in the coeliacomesenteric ganglia and the myenteric and submucosal plexuses of the jejunum, ileum and small colon, and the pathological changes induced in them, were studied in various types of equine dysautonomia. In all forms of dysautonomia, severe and extensive neuron loss and damage occurred in the ileum. In acute and subacute dysautonomia, jejunal neuron loss and damage were severe, but in chronic cases significantly less loss or damage occurred. The damage followed the same pattern in the small colon but it was always less obvious than in the jejunum. The distribution of the damage was uniform within a segment of the intestine. In fatal cases of dysautonomia, the clinical severity and duration of illness seems, in most instances, to be related to the amount of neuronal disruption occurring in the jejunum. Severe disruption results in acute/subacute dysautonomia, while milder damage leads to the chronic form.No case of dysautonomia was encountered in which enteric neuron loss and damage occurred without significant neuronal disruption also occurring in the coeliacomesenteric ganglia.Ileal neuronal damage and loss are not invariably worse than that in the jejunum, and the possible reasons for this, together with the relationship between neuronal damage and possible causes of dysautonomia, are discussed.Abbreviations H&E haematoxylin and eosin Deceased. Formerly of the Moredun Research Institute, 408 Gilmerton Road, Edinburgh, EH17 7JH, UK     

Cecal impaction due to dysautonomia in a llama (Lama glama).

A llama (Lama glama) died after 1 wk of obstipation, lethargy, and rolling. Necropsy showed that the stomach and small intestine were distended with gas and fluid. The cecum was impacted with dry contents and the colon was empty. No gross lesions were found in the wall of the gastrointestinal tract or other organs. Histologic changes consisted of chromatolysis of neurons of autonomic ganglia, enteric plexi, and the accessory cuneate nucleus, consistent with lesions associated with dysautonomia in other domestic animals.     

Canine dysautonomia: two clinical cases

Two clinical cases of canine dysautonomia are described. Two young female neutered dogs were presented with clinical signs including vomiting, diarrhoea, faecal tenesmus, dysphagia and urinary retention. Decreased tear production, dry mucous membranes, bilateral Horner's syndrome, decreased anal sphincter tone and gastrointestinal hypomotility were also observed. Presumptive diagnoses of dysautonomia were made based on the clinical presentation and investigations. Postmortem histopathological examination in one of the cases demonstrated marked depletion of neuronal cell bodies in the intestinal myenteric plexuses and parasympathetic ganglia, confirming the diagnosis in this case. Criteria for aiding the antemortem diagnosis of this rare condition based on clinical observations and diagnostic testing are proposed.     

Dysautonomia and autonomic neuropathies.

The autonomic nervous system can be affected as part of a more diffuse peripheral nerve disease such as inflammatory polyneuropathy or diabetes, or as a primary disease, such as dysautonomia. Dysautonomia is being diagnosed with increasing frequency in dogs and other species in the Midwest. Affected animals present with absence of parasympathetic and autonomic ganglia and brainstem nuclei degenerate with minimal inflammation. The cause is unknown and treatment symptomatic.     

Changes in nasal mucosal innervation in horses with grass sickness

REASONS FOR PERFORMING STUDY: Equine grass sickness is a dysautonomia characterised by widespread destruction of autonomic ganglia, resulting in the clinical signs of dysphagia, constipation, profuse sweating, tachycardia, rhinitis sicca and high mortality rate. Rhinitis sicca is a common finding in horses with the chronic form and we have postulated that alterations in autonomic innervation of the nasal mucosa might underlie this clinical presentation. OBJECTIVES: In this study, the expression and distribution of nerve fibres immunoreactive for calcitonin gene-related peptide (CGRP), substance P (SP), the general neuronal marker protein gene-product 9.5 (PGP 9.5; ubiquitin) and the intermediate neurofilaments (PAN-N; neurorfilaments L, M and H) in the nasal mucosa of normal horses (n = 10) and horses with EGS (n = 18; acute n = 8, subacute n = 3, chronic n = 7) was assessed. METHODS: Innervation density and distribution was investigated in the different groups using standard immunohistochemical techniques. RESULTS: Significant differences were noted when comparing the density and distribution of nerve fibres immunoreactive for PGP 95 and PAN-N, with PGP 95 consistently giving better staining in all groups and at all sites in the nasal mucosa. An apparent increase in the density of innervation was noted for acute vs. normal cases. A significant reduction in the density of innervation was noted only with PAN-N when comparing normal horses and acute cases with the chronic group (P < 0.05). CGRP and SP immunoreactive nerve fibres were typically most abundant in the epithelial and subepithelial layers, but the quality of staining and nerve fibre density was greater for SP, achieving significant difference in several comparisons. The density of innervation for SP was significantly reduced in the chronic group compared to the normal and acute groups (P < 0.01). A significant decrease was noted for CGRP only for the acute and chronic groups (P<0.05). CONCLUSIONS: These results demonstrate a reduction in the expression of the sensory neuropeptides in nasal mucosal innervation as a consequence of equine dysautonomia, and may underlie the clinical presentation of rhinitis sicca noted with this disease. POTENTIAL RELEVANCE: Nasal biopsy may be of use in antemortem diagnosis of grass sickness and identification of mucosal denervation; and might also be useful in the treatment of rhinitis in EGS cases.     

Autonomic dysfunction in a Jack Russell terrier

A 4-year-old Jack Russell terrier was presented with an array of clinical signs suggestive of autonomic dysfunction. Many of the clinical signs were consistent with a diagnosis of dysautonomia; however, both chronicity and resolution of signs contradicted a diagnosis of this disease.     

RADIOGRAPHIC FINDINGS OF CANINE DYSAUTONOMIA IN TWENTY-FOUR DOGS

Canine dysautonomia is an idiopathic condition resulting in loss of autonomic nervous system function. Recently, the prevalence of dogs diagnosed with dysautonomia in the mid-western United States has increased. In this study the medical records and radiographic findings in 24 dogs with dysautonomia were reviewed. A diagnosis of dysautonomia was made in 17 (71%) of the dogs in this study by postmortem examination, the remaining 7 (29%) dogs were diagnosed pharmacologically. The radiographic findings supportive of dysautonomia include aspiration pneumonia, megaesophagus, or a distended stomach, small bowel, or urinary bladder. In some instances, the disease radiographically mimicked other disorders of the gastrointestinal tract, including mechanical obstruction.     

Feline dysautonomia — The Key-Gaskell syndrome

Sir:- In 1981, Key and Gaskell in the United Kingdom recognised a new disease in cats which subsequently became known as the Key-Gaskell Syndrome.⁽¹⁾ The incidence of this condition increased in the United Kingdom during 1982, and other workers described the clinical signs in more detail and were able to relate certain features of the disease to changes in the autonomic ganglia⁽³⁾⁽⁴⁾ Recently, the NZVA Small Animal Society was asked by the World Small Animal Veterinary Association for any evidence as to its presence in New Zealand. The purpose of this letter is to provide information on feline dysautonomia (Key-Gaskell Syndrome), which it is felt may assist veterinary practitioners to recognise the condition and determine if it occurs in this country.     

Diabetes mellitus-related morphoquantitative changes in the celiac ganglion neurons of the dog

Diabetes mellitus is the most common endocrine disturbance of domestic carnivores and can cause autonomic neurological disorders, although these are still poorly understood in veterinary medicine. There is little information available on the quantitative adaptation mechanisms of the sympathetic ganglia during diabetes mellitus in domestic mammals. By combining morphometric methods and NADPH-diaphorase staining (as a possible marker for nitric oxide producing neurons), type I diabetes mellitus-related morphoquantitative changes were investigated in the celiac ganglion neurons in dogs. Twelve left celiac ganglia from adult female German shepherd dogs were examined: six ganglia were from non-diabetic and six from diabetic subjects. Consistent hypertrophy of the ganglia was noted in diabetic animals with increase of 55% in length, 53% in width, and 61.5% in thickness. The ordinary microstructure of the ganglia was modified leading to an uneven distribution of the ganglionic units and a more evident distribution of axon fascicles. In contrast to non-diabetic dogs, there was a lack of NADPH-diaphorase perikarial labelling in the celiac ganglion neurons of diabetic animals. The morphometric study showed that both the neuronal and nuclear sizes were significantly larger in diabetic dogs (1.3 and 1.39 times, respectively). The profile density and area fraction of NADPH-diaphorase-reactive celiac ganglion neurons were significantly larger (1.35 and 1.48 times, respectively) in non-diabetic dogs compared to NADPH-diaphorase-non-reactive celiac ganglion neurons in diabetic dogs. Although this study suggests that diabetic neuropathy is associated with neuronal hypertrophy, controversy remains over the possibility of ongoing neuronal loss and the functional interrelationship between them. It is unclear whether neuronal hypertrophy could be a compensation mechanism for a putative neuronal loss during the diabetes mellitus.     

Immunohistochemical characteristics of neurons supplying the porcine bulbourethral gland

In the male pig, the bulbourethral gland (BG) is a particulary well developed accessory genital gland (AGG) which produces complex secretion contributing to the fluid component of semen. The secretory and motor function of AGGs is thought to be under the autonomic nervous system control. Although relatively much is known about the innervation of the prostate gland and, to a lesser degree, of the seminal vesicle, the paucity of data dealing with the innervation of BG is striking. Therefore, combined retrograde tracing and double-labelling immunofluorescence have been used to investigate the distribution and immunohistochemical properties of autonomic and primary afferent neurons projecting to this gland in the pig. BG-projecting neurons were found in some ipsilateral (I) and contralateral (C) sympathetic chain ganglia (SChG), the caudal mesenteric ganglion (CaMG), pelvic ganglia (PG) and some dorsal root ganglia (DRG). Immunohistochemistry revealed that the vast majority of CaMG and SChG BG-projecting neurons contained tyrosine hydroxylase (TH) and dopaminebeta-hydroxylase (DbetaH), and some neuropeptides including neuropeptide Y (NPY), somatostatin (SOM) and galanin (GAL). Three subpopulations of PG neurons supplying BG could be distinguished: 1) cholinergic neurons [vesicular acetylcholine transporter (VAChT)-positive] which also contained vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), SOM and NPY, 2) adrenergic neurons (TH-positive) which also stained for NPY, GAL or leu5-enkephalin (LEU), and 3) non-adrenergic, non-cholinergic neurons (NANC). DRG BG-projecting neurons contained mostly substance P (SP) and/or calcitonin gene-related peptide (CGRP) which sometimes colocalized with GAL. The possible functional significance of the substances found within the neurons is discussed.     

Experimental study on the location of neurons associated with the first sacral sympathetic trunk ganglion of the pig

The neurons associated with the left first sacral sympathetic trunk ganglion (STG S1), an autonomic ganglion particularly concerned in the innervation of the smooth and striated musculature associated with pelvic organs, were identified in the pig, using the non-trans-synaptic fluorescent retrograde neuronal tracer Fast Blue. The labelled neurons were located mostly ipsilaterally, in the intermediolateral nucleus of the spinal cord segments T10-L5, in the sympathetic trunk ganglia L3-Co1, in the caudal mesenteric ganglia, in the pelvic ganglia, and in the spinal ganglia T13-S4. Our results could indicate the existence of visceral neuronal circuits concerning the ganglia of the sympathetic trunk and the caudal mesenteric, pelvic and spinal ganglia with or without the intervention of the central nervous system, whose identification and preservation during surgical treatments could be helpful in reducing the risk of subsequent urinary and sexual disfunctions.     

Diagnosis of dysautonomia in a cat by autonomic nervous system function testing

Clinical signs of dysautonomia, including dilated pupils, dry mucous membranes, and megaesophagus, were observed in a cat. The diagnosis was confirmed by use of autonomic nervous system function testing including 0.1% pilocarpine and physostigmine ocular response tests, plasma catecholamine assays, and cardiovascular responses to various perturbations intended to elicit autonomic responses. The cause of the autonomic dysfunction was not ascertained, and the cat was euthanatized after 5 weeks of unsuccessful treatment with pilocarpine, metoclopramide, prochlorperazine, and parenteral nutrition.     

Multisystemic chromatolytic neuronal degeneration in a Cairn terrier pup

In a four-month-old female Cairn terrier with mild episodic paraparesis, a multisystemic chromatolytic degeneration affected widespread neuronal populations in the brain and spinal cord as well as spinal, autonomic, and enteric ganglia. There was little axon degeneration or cell body loss, and the latter findings may explain the mild clinical signs. Among affected perikarya the extent and distribution of chromatolysis varied. While peripheral lysis of Nissl substance occurred often in spinal motoneurons, central chromatolysis was frequent in brain stem nuclei, and patchy Nissl loss appeared in some neurons including those in the cerebral cortex and spinal dorsal horns. Although prior studies of various chromatolytic neurodegenerations often have demonstrated characteristic massings of neurofilaments, the major, and invariable ultrastructural finding in this study was dispersion and loss of ribosomes. Neurofilamentous accumulations were observed less consistently. The clinical and pathologic findings in this pup were compared and constrasted with those made in prior studies of chromatolytic neurodegenerations.     

Five cases of canine dysautonomia in England (2004 to 2006)

Canine dysautonomia was diagnosed definitively in five dogs by histopathology. All dogs were seen between June 2004 and July 2006 and originated from south-east England; four dogs originated from an urban area and one from a rural area. Of the urban dogs, one had recently visited Scotland and one had visited a kennel in a rural area nearby. Acute-onset but progressive vomiting, diarrhoea, depression and inappetence were the most common presenting clinical signs. Reduced or absent anal tone, dysuria, absence of pupillary light reflexes with intact vision, mydriasis, decreased corneal sensitivity and nictitating membrane protrusion were among the most frequent neurological findings. Abnormalities in pharmacological autonomic and physiological function testing (including orthostatic hypotension in two dogs) and diagnostic imaging studies were detected in some of the animals. All dogs failed to respond adequately to treatment, and given the poor prognosis, they were eventually euthanased. Histopathology identified marked chromatolysis of ganglion cell bodies. This case series emphasises that dysautonomia should be considered when a dog is presented in the UK with acute- or subacute-onset gastrointestinal signs and compatible physical and neurological abnormalities.     

Postdiaphragmatic disposition of the pars sympathica and major autonomic ganglia of the sheep (Ovis aries)

Extract

Morphological study of the postdiaphragmatic distribution of the sympathetic trunk and the composition of the main autonomic ganglia and plexuses of the abdominal and pelvic cavities of the sheep are of prime importance for clinical and other experimental work. Most of the veterinary anatomical textbooks are extremely deficient in this area. A few words of explanation have occasionally been mentioned, assuming that possibly there is no significant difference in the pattern of distribution of the abdominal and pelvic autonomics from those of the ox.     

"Shaker" calf syndrome: a newly recognized inherited neurodegenerative disorder of horned Hereford calves

The clinical and pathological features of a newly recognized, inherited neurodegenerative disorder in horned Hereford calves are described. The disorder is expressed in newborns by tremulous shaking of the head, body and tail, difficulty in rising, a wobbly spastic gait, and aphonia. Transient improvement is followed by deterioration and progressive spastic paraplegia. Generalized tremors can be induced easily by a variety of stimuli, and spinal reflexes may be exaggerated or depressed. The major pathological finding is an excessive accumulation of neurofilaments within neurons of the central, peripheral, and autonomic nervous systems. The involvement of multiple systems of neurons and the similarity with some forms of human motor neuron disease and spinocerebellar degeneration suggest that this unique bovine disease may serve as a suitable animal model for these human neurodegenerative disorders.