Family aggregation analysis shows a possible heritable background of equine grass sickness (dysautonomia) in a Hungarian stud population.

Equine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a century ago, several factors, such as the phenotype, intestinal microbiome, environment, management and climate, have been supposed to be associated with the increased risk of dysautonomia. In this retrospective study, we examined the possible involvement of genetic factors. Medical and pedigree datasets regarding 1,233 horses with 49 affected animals born during a 23-year period were used in the analysis. Among the descendants of some stallions, the proportion of animals diagnosed with dysautonomia was unexpectedly high. Among males, the odds of dysautonomia were found to be higher, albeit not significantly, than among females. Significant familial clustering (genealogical index of familiality, P = 0.001) was observed among the affected animals. Further subgroups were identified with significant (P < 0.001) aggregation among close relatives using kinship-based methods. Our analysis, along with the slightly higher disease frequency in males, suggests that dysautonomia may have a genetic causal factor with an X-linked recessive inheritance pattern. This is the first study providing ancestry data and suggesting a heritable component in the likely multifactorial aetiology of the disease.

Ganglion Cytology: A Novel Rapid Method for the Diagnosis of Equine Dysautonomia.

Equine dysautonomia (grass sickness) is characterized by autonomic neuronal degeneration and is often fatal. As outbreaks occur, rapid diagnosis is essential but confirmation currently requires histological examination. This study evaluated diagnostic accuracy of cytological examination of cranial cervical ganglion (CCG) scrapings for dysautonomia diagnosis. CCG smears from 20 controls and 16 dysautonomia cases were stained with May-Grünwald Giemsa (MGG), hematoxylin and eosin (HE), and cresyl fast violet (CFV), with HE-stained histological sections of CCG as gold standard for diagnosis. Examining all 3 stains together, the sensitivity and specificity were 100%. Occasional individual smears (4/107, 3.7%) were nondiagnostic due to low cellularity, and in a few individual smears the final diagnosis was correct but more tentative (CFV: 5/33 [15.1%], HE: 2/34 [5.9%], and MGG: 4/36 [11.1%]), due to low cellularity or suboptimal cell morphology. CCG cytology was considered reliable for rapid postmortem diagnosis of equine dysautonomia, particularly using MGG.

Equine Dysautonomia.

Equine dysautonomia (ED; also known as equine grass sickness) is a neurological disease of unknown cause, which primarily affects grazing adult horses. The clinical signs reflect degeneration of specific neuronal populations, predominantly within the autonomic and enteric nervous systems, with disease severity and prognosis determined by the extent of neuronal loss. This review is primarily focused on the major clinical decision-making processes in relation to ED, namely, (1) clinical diagnosis, (2) selection of appropriate ancillary diagnostic tests, (3) obtaining diagnostic confirmation, (4) selection of treatment candidates, and (5) identifying appropriate criteria for euthanasia.

Lipofuscin accumulates in ganglionic neurons in chronic equine dysautonomia.

Lipofuscin is a complex mixture of highly oxidized, cross-linked macromolecules that accumulates in neurons with age and some neurodegenerative diseases. Equine dysautonomia (ED) is a polyneuropathy that mainly affects autonomic and enteric nervous systems, resulting in alimentary tract dysfunction. Our main aim was to determine whether neuronal lipofuscin increased with increasing duration of ED. We investigated the prevalence of lipofuscin in cranial cervical ganglia of horses with acute (AED), subacute (SED), and chronic ED (CED), young controls (of similar age to ED cases), and aged controls (n = 8 per group). We used Schmorl stain for histologic detection of lipofuscin and assessed its accumulation in neurons using image analysis software. The percentage of neurons positive for lipofuscin increased with age in individual groups and all groups combined (p < 0.001). There were fewer positive neurons in AED and SED compared to aged controls (p < 0.001) and more in CED than AED cases (p = 0.042) and young controls (p = 0.012). We found a strong positive correlation between percentage positive neurons and percentage positive area of the neuron containing lipofuscin for combined groups (p < 0.001). Although neuronal lipofuscin increased in cranial cervical ganglion in CED cases, it remains to be determined whether this is a cause or consequence of neuronal degeneration.

Dysautonomia in a six-year-old mule in the United States.

Equine dysautonomia, also known as equine grass sickness (EGS), is a well documented disease in several countries. To the authors' knowledge, EGS has not been reported previously in North America. This report describes EGS in a 6-year-old female mule in the USA. Failure initially to consider EGS resulted in a delayed diagnosis. EGS should be considered as a differential diagnosis and appropriate diagnostic tests performed in similar cases in North America.

Dysautonomia in 53 cats and dogs: retrospective review of clinical data and outcome.

BACKGROUND: Dysautonomia is a disease characterised by degeneration of autonomic neurons. METHODS: The aim of this study was to perform a retrospective multicentre review of clinical data relating to cats and dogs diagnosed with dysautonomia and to evaluate their outcome. RESULTS: Cats (n=34) and dogs (n=19) with clinical signs consistent with dysautonomia were considered for this retrospective study. Reported clinical findings included oesophageal and gastrointestinal dysmotility and distension, urinary retention, reduced or absent tear production, third eyelid protrusion and inappropriate mydriasis. Treatment was supportive and included gastrointestinal prokinetics, feeding tube placement (oesophageal and percutaneous endoscopic gastrostomy tubes) and medications to treat urinary retention. The survival to discharge was 29 per cent in cats and 47 per cent in dogs. The overall survival in cats was 21 per cent and that in dogs was 32 per cent. Survival of greater than 2 years was seen in six cats and in three dogs. CONCLUSION: This paper illustrates that some animals are able to survive this disease and can have a good long-term prognosis, which is an infrequently reported finding for this disease.

Echocardiographic evaluation of dogs with dysautonomia.

OBJECTIVE: To describe echocardiographic findings in dogs with dysautonomia. DESIGN: Prospective case series: ANIMALS: 20 dogs with dysautonomia (13 confirmed during necropsy and 7 with results of antemortem testing [tear production, pilocarpine response test, atropine response test, and ID histamine response] supportive of the diagnosis). PROCEDURES: Dogs with dysautonomia were evaluated by use of echocardiography, and M-mode measurements were obtained on all dogs. A dobutamine response test was performed on 1 dog, starting at a rate of 1 microg/kg/min and doubling the rate every 15 minutes until fractional shortening (FS) increased to > 2 times the baseline value. RESULTS: Evidence of systolic dysfunction was detected in 17 of 20 dogs with dysautonomia, as determined on the basis of FS (median, 17.9%; range, 4.0% to 31.1%). Left ventricular internal dimension during diastole or left ventricular internal dimension during systole was enlarged in 4 of 20 and 14 of 20 dogs, respectively. Enlargement of the left atrium or aorta was identified in 3 of 15 and 1 of 15 dogs in which it was measured, respectively. Administration of dobutamine at a rate of 4 microg/kg/min resulted in dramatic improvement in FS (increase from 4% to 17%) in the 1 dog tested. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that echocardiographic evidence of diminished systolic function was common in dogs with dysautonomia. Whether the diminished function was a result of sympathetic denervation or myocardial hibernation was unclear, although myocardial hibernation was more likely.

A study of residual lesions in horses that recovered from clinical signs of chronic equine dysautonomia.

BACKGROUND: Equine dysautonomia (ED) causes degeneration and loss of autonomic neurons. Approximately 50% of chronic cases recover, but it is unclear how they survive neuronal loss. OBJECTIVES: To assess lesions, autonomic neuron numbers, interstitial cells of Cajal (ICC), and neurodegeneration in recovered cases. ANIMALS: Thirteen cases (group ED), euthanized 10.3 ± 5.2 (1-16) years from diagnosis and 6 age-matched controls (group C). METHODS: Prospective, case control; routine post mortem examination, neuron counts in peripheral and enteric ganglia and immunohistochemical assessment of neural networks (Protein gene product [PGP] 9.5), ICC (c-kit), and neurodegeneration (beta-amyloid precursor protein and ubiquitin) in intestine. RESULTS: Postmortem findings in group ED were small intestinal dilation (4/12, 33%) and muscular hypertrophy (4/12, 33%), and gastric mucosal hypertrophy (3/11, 27%) and ulceration (4/11, 36%). Neuron density was lower in group ED (mean 39% lower for cranial cervical ganglion [P < .001], median 44% lower in celiacomesenteric ganglion [P = .01]). In intestine, neuronal depletion was worst in ileum (median 100% lower in submucosal plexus [P < .001], 91% lower in myenteric plexus [P = .004]). Group ED had less PGP 9.5 staining in ileal myenteric plexus (mean 66% lower [P = .04]) and circular muscle (median 75% lower [P = .006]). In ileum, there was less c-kit staining in myenteric plexus (median 57% lower [P = .02]) but not muscularis externa. Beta-amyloid precursor protein and ubiquitin results were not indicitive of neurodegeneration. CONCLUSIONS AND CLINICAL IMPORTANCE: Intact ICC in muscularis externa might help maintain motility after neuronal loss. Treatment supporting ICC function warrants investigation.

Autoimmune myasthenia gravis and dysautonomia in a dog.

A two-year-old male entire border collie dog was evaluated for a short history of mixed bowel diarrhoea, coughing, vomiting and stranguria. Physical examination revealed dyspnoea with increased ventral lung sounds and a flaccidly distended bladder. Neurological examination revealed poor pupillary light reflexes, an absent gag reflex and a poor anal tone. Thoracic radiography was consistent with megaoesophagus and aspiration pneumonia. Clinicopathological testing revealed an elevated muscular nicotinic acetylcholine receptor antibody titre. The dog was euthanased because of clinical deterioration. Cerebrospinal fluid (CSF) collected immediately post-mortem revealed macrophagic pleocytosis. Post-mortem histopathological examination was consistent with dysautonomia. This is the first report of coexisting autoimmune myasthenia gravis and dysautonomia in a non-human species. The concomitant diseases may suggest a common immunopathological aetiology.

Development of a clinical prediction score for detection of suspected cases of equine grass sickness (dysautonomia) in France.

Equine grass sickness (EGS) (equine dysautonomia) is a neurodegenerative condition of grazing equines. Pre-mortem diagnosis of EGS is a challenge for practitioners as definitive diagnosis requires ileal/myenteric lymph node biopsies. This study aimed to develop a clinical score that could be used by practitioners to improve the detection of acute or subacute EGS cases in the field. Suspected EGS cases were declared by veterinary practitioners. A case was classified as confirmed positive if ileal or rectal biopsy samples showed neuronal degeneration typical of EGS. A semi-quantitative scoring system, including epidemiological and clinical data, was created to attempt to classify suspected EGS horses into confirmed positive or negative cases. Each variable was weighted based on a boosted regression trees model, while taking into account its clinical relevance. Twenty-eight EGS cases were confirmed by biopsy during the entire study period. The best cut-off value for the score to have a high sensitivity while maximizing specificity was 8, with a sensitivity of 100% and a specificity of 53%. In our dataset, 77% of animals would be correctly classified with this cut-off value of 8. Highest sensitivity was chosen in order to detect the highest number of potential cases. Our score represents an inexpensive and useful tool to aid in the identification of suspected EGS cases in the field and selection for further diagnostics procedures to confirm or rule out the disease. Application of the score to larger populations of animals would be required to further adapt and refine the score.

Alterations in amino acid status in cats with feline dysautonomia.

Feline dysautonomia (FD) is a multiple system neuropathy of unknown aetiology. An apparently identical disease occurs in horses (equine grass sickness, EGS), dogs, rabbits, hares, sheep, alpacas and llamas. Horses with acute EGS have a marked reduction in plasma concentrations of the sulphur amino acids (SAA) cyst(e)ine and methionine, which may reflect exposure to a neurotoxic xenobiotic. The aim of this study was to determine whether FD cats have alterations in amino acid profiles similar to those of EGS horses. Amino acids were quantified in plasma/serum from 14 FD cats, 5 healthy in-contact cats which shared housing and diet with the FD cats, and 6 healthy control cats which were housed separately from FD cats and which received a different diet. The adequacy of amino acids in the cats' diet was assessed by determining the amino acid content of tinned and dry pelleted foods collected immediately after occurrences of FD. Compared with controls, FD cats had increased concentrations of many essential amino acids, with the exception of methionine which was significantly reduced, and reductions in most non-essential amino acids. In-contact cats also had inadequate methionine status. Artefactual loss of cysteine during analysis precluded assessment of the cyst(e)ine status. Food analysis indicated that the low methionine status was unlikely to be attributable to dietary inadequacy of methionine or cystine. Multi-mycotoxin screening identified low concentrations of several mycotoxins in dry food from all 3 premises. While this indicates fungal contamination of the food, none of these mycotoxins appears to induce the specific clinico-pathologic features which characterise FD and equivalent multiple system neuropathies in other species. Instead, we hypothesise that ingestion of another, as yet unidentified, dietary neurotoxic mycotoxin or xenobiotic, may cause both the characteristic disease pathology and the plasma SAA depletion.

Canine dysautonomia in a litter of Havanese puppies.

Canine dysautonomia is a sporadic, generally fatal disease that rarely affects groups of related animals. Four 10-week-old Havanese puppies from a litter of 5 developed clinical signs of canine dysautonomia. The 4 affected dogs were exposed to an outdoor environment, whereas the fifth littermate was not exposed to the outdoors and remained clinically healthy. Clinical signs of dysautonomia developed 10-16 days after going outside the house. An unrelated dog also developed dysautonomia after exposure to 1 of the affected Havanese littermates. All 5 dogs had morphological changes consistent with dysautonomia (widespread neuronal degeneration in autonomic ganglia, select brainstem nuclei, and ventral horn motor neurons). Differential diagnoses were excluded through negative toxicological evaluation, fecal parasite screening, negative Canine distemper virus reverse transcription polymerase chain reaction, fluorescent antibody testing, attempted virus isolation, and electron microscopy. The 5 affected dogs were in the Kansas City, Missouri area, where there is a high incidence of dysautonomia.

Imaging findings in 11 cats with feline dysautonomia.

Dysautonomia is caused by degeneration of the autonomic ganglia. Failure of the autonomic system affecting the gastrointestinal and urinary tracts can cause oesophageal distension and/or dysfunction, gastric and bowel distension and hypomotility, and urinary bladder distension. The aim of this retrospective study was to describe diagnostic imaging findings in cats with dysautonomia. Common findings were megaoesophagus and/or oesophageal dysfunction, gastric distension and signs of intestinal ileus. Associated aspiration pneumonia and megacolon appeared less commonly. Although diagnostic imaging findings are not specific for this disease, if findings in multiple systems are detected, along with consistent clinical signs and neurological deficits, dysautonomia should be considered among the differential diagnosis.

Key-Gaskell syndrome in Brazil: first case report / Síndrome de Key-Gaskell: primeiro relato de caso no Brasil

Feline dysautonomia is a devastating disease characterized by neuronal degeneration in autonomic ganglia that results in clinical signs related to dysfunction of the sympathetic and parasympathetic nervous systems. The cause is unknown and this disease has a poor prognosis and no definitive treatment. Most reports have been described in few countries around the world, but the prevalence may be underestimated in countries like Brazil. This study describes the progression and clinicopathological changes of dysautonomia in a 17-month-old female Brazilian shorthair cat...

Disautonomia felina é uma doença devastadora, caracterizada por degeneração neuronal em gânglios autonômicos, a qual resulta em sinais clínicos relacionados à disfunção dos sistemas simpático e parassimpático. Sua causa é desconhecida, o prognóstico desfavorável e não há tratamento definitivo disponível. A maioria dos relatos foi descrita em países ao redor do mundo, mas sua prevalência pode estar subestimada em países como o Brasil. Este estudo descreve a progressão e as alterações clínico-patológicas da disautonomia em um gato de pelo curto brasileiro, do sexo feminino, de 17 meses de idade...