Grass Sickness is a debilitating and often fatal disease affecting the gastrointestinal tract of horses. It is characterized by damage to the autonomic nervous system, leading to impaired gut motility and digestive function. The condition is classified into acute, subacute, and chronic forms, each varying in severity and progression. The exact cause of Grass Sickness remains unknown, though it is believed to involve a combination of environmental, dietary, and microbial factors. Common clinical signs include colic, difficulty swallowing, and weight loss. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, pathophysiology, and potential risk factors associated with Grass Sickness in horses.
Böhnel H, Wernery U, Gessler F.Botulism is caused by different types of Clostridium botulinum, a soil bacterium. Equine grass sickness (equine dysautonomia) is suspected of being a clinical form of this disease. On a stud where this disease occurred twice within 8 months, grass and soil samples and necropsy specimens of one horse were tested for the presence of bacterial forms and toxin of C. botulinum. Different types and type mixtures (A-E) of C. botulinum and botulinum neurotoxin were found. For the first time, it has been shown that green grass blades contain botulinum toxin. The results support the hypothesis that equi...
McGorum BC, Wilson R, Pirie RS, Mayhew IG, Kaur H, Aruoma OI.The aetiopathogenesis of equine grass sickness (EGS) is unknown. The role of free radical-mediated neuronal damage has not previously been investigated in this condition. Objective: To investigate the potential contribution of oxidative damage and antioxidant status to neurodegeneration in EGS. Methods: Systemic levels of surrogate biomarkers were determined in 10 horses with acute EGS and in 2 control populations; 10 healthy horses co-grazing with the 10 EGS horses at the onset of clinical disease, and 10 healthy mares grazing where EGS has not been reported. Results: EGS horses had alteratio...
Bailey SR, Marr CM, Elliott J.Acute laminitis has been associated with the release of compounds, as yet unidentified, produced by hindgut fermentation which affect blood flow to the digit. The objectives of this study were to identify amine compounds in equine caecal and colonic contents, some of which are known to have vasoactive properties. In addition, the concentrations of amines in caecal contents of horses fed either grass or hay diets were compared. Fifteen amines were identified in equine hindgut contents in concentrations greater than 1 microM. The caecal concentrations of phenylethylamine, isoamylamine, cadaverin...
Prince D, Corcoran BM, Mayhew IG.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. Objective: In this study, the expression and distribution of nerve fibres immunoreactive for calcitonin gene-related peptide (CGRP), substance P (SP), the general neuronal ...
Fintl C, Milne EM, McGorum BC.To determine whether urinalysis can aid the diagnosis of equine grass sickness, samples of urine from 15 horses with acute grass sickness, eight horses with subacute grass sickness, 17 co-grazing horses and 17 stabled control horses were analysed. The samples from all of the horses with grass sickness had a significantly higher specific gravity, higher protein and creatinine concentrations and a significantly lower pH; the samples from the horses with acute grass sickness also had significantly higher glucose concentrations. These differences may support a diagnosis of grass sickness but they ...
McGorum BC, Anderson RA.To test the hypothesis that equine grass sickness may be associated with the ingestion of cyanogenic glycosides from white clover (Trifolium repens), the concentrations of whole blood cyanide, and plasma and urinary thiocyanate, the main metabolite of cyanide, were measured in 12 horses with acute grass sickness and 10 horses with subacute grass sickness, and in 43 control horses, of which 21 were co-grazing with cases of acute grass sickness, 12 grazed pastures where grass sickness had not been reported, and 10 were stabled horses. The healthy horses which grazed with cases of acute grass sic...
Fintl C, McGorum BC.Brotizolam, acetylcysteine and aloe vera gel were evaluated as ancillary treatments for 29 cases of equine grass sickness. None of the treatments had any significant beneficial effect on the survival of the horses. However, 11 of 13 horses with mild chronic grass sickness survived solely with intensive nursing care.
Hudson N, Mayhew I, Pearson G.Equine dysautonomia (grass sickness) is a frequently fatal disease of horses characterised by intestinal stasis. Interstitial cells of Cajal (ICC) are the pacemakers and mediators of neurotransmission in the gastrointestinal tract. Impaired ICC-mediated control of motility has been implicated in intestinal disorders in laboratory mammals, humans and in equine grass sickness. The aim of this study was to compare the in vitro electrical properties of ileum from grass sickness cases with horses free from gastrointestinal disease. Intracellular microelectrode recordings were made from smooth muscl...
Chandler KJ, Dixon RM.Urinary cortisol and creatinine concentrations, and the cortisol:creatinine ratio were compared between 12 healthy horses (group 1), 13 horses with Cushing's disease (group 2), and eight horses with dysautonomia syndrome (equine grass sickness) (group 3). The mean (sd) urinary cortisol concentrations were 112 (55.7), 250 (357) and 864 (526) nmol/litre in groups 1, 2 and 3, respectively; the mean (sd) urinary creatinine concentrations were 18.9 (7.3), 12.0 (6.7) and 45.2 (26.4) nmol/litre in groups 1, 2 and 3, respectively, and the mean (sd) ratios were 6.1 (2.6), 19.8 (23.8) and 21.3 (14.5) (x...
Garrett LA, Brown R, Poxton IR.This study compares quantitatively the microbiota of the gastrointestinal tract of healthy horses with that of horses with equine grass sickness (EGS). Faecal and ileal samples were cultured quantitatively on selective and non-selective media. Confirmed anaerobes were identified to species level. Overall faecal counts gave a ratio of aerobes:anaerobes of approximately 1:1. However, the mean counts in healthy horses of 4.4x10(8) aerobes:3.7x10(8) anaerobes per gram wet weight were different from counts in EGS (means were 10-100-fold higher), with statistically significant differences for the an...
Hunter LC, Poxton IR.The aetiology of equine grass sickness (EGS) is still unknown. There is increasing evidence that toxicoinfection with Clostridium botulinum type C is involved. Epidemiological evidence shows that resistance to EGS can occur in older horses and those that have been on a particular pasture for longer or have been in prior contact with the disease. This resistance may be in the form of an immune response to the aetiological agent. Levels of systemic antibodies to the surface antigens of C. botulinum type C (using the closely related and safe C. novyi type A as a phenotypic marker) and to the botu...
McCarthy HE, Proudman CJ, French NP.The geographical spread of grass sickness between 1909 and 1999, particularly in England and Wales, is described, and the experimental investigations to identify a causal agent are summarised. The epidemiological techniques used to investigate grass sickness vary from clinical observations, to more advanced methods such as case-control studies using logistic regression analyses. Several risk factors for grass sickness have been reported consistently (age, time of year and recent movement to new pasture or premises) and several others have been reported for which the findings remain inconsisten...
Hudson N, Mayhew I, Pearson G.Equine dysautonomia (grass sickness) is a common, frequently fatal disease of horses characterised by dysfunction of the gastrointestinal tract. Interstitial cells of Cajal are the c-Kit-immunoreactive cells responsible for the generation of pacemaker activity in gastrointestinal smooth muscle. Impairment of this pacemaker action has been implicated in several motility disorders in humans and laboratory mammals. The aim of this study was to test the hypothesis that changes in interstitial cells of Cajal may be involved in the pathophysiology of the intestinal dysfunction observed in equine gra...
Hahn CN, Mayhew IG, de Lahunta A.Equine grass sickness (EGS) is an acquired disease of unknown aetiology affecting horses kept at grass. The disease is characterised by postganglionic sympathetic and parasympathetic neuronal pathology and is categorised as a dysautonomia. This study undertook a systematic examination of brain stem cranial nerve nuclei in 59 cases of EGS. Pathology consisting of neuronal chromatolysis was most consistently noted in the lower motor neurons of the general visceral efferent nucleus of CN III and X and the general somatic efferent nuclei of CN III, V, VII and XII. The prevalence of chromatolysis d...
McGorum BC, Kirk J.To determine whether equine dysautonomia (ED) is associated with alterations in plasma amino acid metabolism, plasma amino acid profiles were determined for horses with acute (n = 10), subacute (n = 6) and chronic (n = 7) ED and for healthy cograzing horses (n = 6) and control horses (n = 10). Horses with acute ED had perturbations in plasma amino acid profiles resembling those of severe protein malnutrition. In addition, horses with ED and cograzing healthy horses had depletion of the plasma sulphur amino acids cyst(e)ine and methionine. As similar plasma amino acid perturbations occur in sub...
Marrs J, Small J, Milne EM, John HA.Hepatocellular and hepatobiliary damage was assessed in equine acute, subacute and chronic grass sickness cases (AGS, SAGS, CGS). Histopathological analysis showed that even in some early AGS cases enlarged hepatocytes, hepatocyte vacuolation indicative of lipid accumulation (steatosis), intrahepatocyte, canalicular and periportal deposition of pigments, frequent leucocyte infiltration and cholangitis occurred. Analysis of serum indicated significantly increased levels of unconjugated bilirubin in all groups and conjugated bilirubin in AGS and SAGS groups, increased levels of bile acids in som...
Hahn CN, Mayhew IG.The effect of an ocular administration of the alpha-1 adrenergic agonist phenylephrine was studied in 23 cases of grass sickness and 12 control horses. In the horses with grass sickness there was a significantly greater mean increase in the size of the palpebral fissure, as measured by the change in the angle of the eyelashes to the head observed from a frontal view.
John HA, Marrs J, Laffling AJ.In the autonomic nervous system (ANS) of equine grass sickness (GS) cases, some neurones show abnormal changes while neighbouring neurones are unaffected. To test whether noradrenergic neurones showed variable susceptibility to the GS toxin in culture, clonally-derived populations isolated from the same fetal thoracic sympathetic chain ganglion were challenged with plasma from GS cases previously shown to induce ANS damage when injected into normal horses. During the early stages of exposure to toxic plasma, cells within a clonal population showed variable susceptibility ranging from no obviou...
John HA, Laffling AJ, Marrs J, Baird A, Jat PS, Holdstock NB, Rossdale PD.To enable direct testing of a range of potential toxins or pathogens that might be involved in grass sickness, equine thoracic sympathetic chain ganglion cell lines were established from primary cell cultures by retroviral-mediated transduction of the temperature-sensitive mutant of the establishment oncogene encoding SV40 large T antigen. Morphological and behavioral features, temperature dependence, and immunocytochemical characteristics of the cell lines were investigated. The majority of cells were noradrenergic neurons in which dopamine-beta-hydroxylase, the enzyme that catalyzes norepine...
Perkins JD, Bowen IM, Else RW, Marr CM, Mayhew IG.The parasympathetic terminal cardiac ganglia were examined in three normal horses and in five horses with grass sickness. Histopathological changes, consistent with those observed in other ganglia of horses with grass sickness, were identified in the terminal cardiac ganglia of the affected horses. A functional analysis of cardiac autonomic control by time domain analysis (TDA) of heart rate variability was applied to eight horses with grass sickness, and double-paired to 16 normal horses on the basis of their age, sex and breed, and the time of day at which the electrocardiographs were obtain...
Hunter LC, Miller JK, Poxton IR.The cause of grass sickness, an equine dysautonomia, is unknown. The disease usually results in death. Gastrointestinal (GI) dysfunction is a common clinical manifestation in all forms of the disease. It is generally thought that equine grass sickness (EGS) is caused by an ingested or enterically produced neurotoxin which is absorbed through the GI tract. Clostridium botulinum was first implicated as a causative agent when it was isolated from the GI tract of a horse with EGS in 1919. The aim of the present study was to investigate the hypothesis that EGS results from toxicoinfection with C. b...
Greet TR, Whitwell KE.Twenty-five horses, suspected on clinical grounds of having grass sickness, were given a barium swallow. Using image intensification the passage of the barium bolus was followed radiographically from the pharynx to the stomach. All 18 horses in which grass sickness was later confirmed at post mortem examination showed defective oesophageal motility. Although the specificity of the abnormality could not be proven, the technique offers a valuable aid to the ante mortem diagnosis of grass sickness.
Edwards SE, Martz KE, Rogge A, Heinrich M.Equine dysautonomia or equine grass sickness (EGS), as it is more commonly known, is a usually fatal disease of equids of uncertain etiology, although associated with grazing, that affects the autonomic and enteric nervous system. Lowered gastrointestinal motility, leading to paralysis of the gut, is one of the main symptoms of EGS. Previous studies have implicated anaerobic bacteria, notably Clostridium botulinum, but what triggers the severe bacterial infestations remains enigmatic. We hypothesized that a detailed comparison of soil mineral and botanical composition of EGS and control sites ...
Milne EM, Doxey DL, Woodman MP, Cí·¯ord D, Pearson RA.A clinical trial was carried out to determine the effect of cisapride on rate of passage of digesta and clinical parameters in horses with chronic grass sickness. Sixteen horses were given intramuscular cisapride (0.1 mg kg-1 three times daily) (group I), and 15 received oral cisapride (0.8 mg kg-1 three times daily) (group O). A liquid-phase marker (cobalt-EDTA) and a solid-phase marker (polystyrene pellets) were given by stomach tube at the beginning of each of three consecutive 7 day periods, i.e., before, during and after cisapride therapy. Seven horses in each group completed the rate of ...
Doxey DL, Milne EM, Ellison J, Curry PJ.Responses to questionnaires were received from 31 owners of horses or ponies treated for chronic grass sickness (dysautonomia). Contrary to previous opinions the respondents indicated that the majority of the animals were capable of strenuous work, had regained the weight they had lost and, apart from a few residual problems such as difficulty in coping with dry fibrous food, had returned to a normal life. They had recovered slowly and had involved the owners in considerable extra work, but all the owners indicated that they considered the effort to have been worthwhile.
Milne EM, Woodman MP, Doxey DL.Forty-five cases of chronic grass sickness were given scores for selected clinical measurements when they were first examined, to assess their value in predicting survival. Sixteen cases survived. The clinical scores for the degree of dysphagia, appetite, colic and the degree of reduction in gut sounds were significantly lower in the survivors than in the non-survivors. In addition, only the non-survivors had severe rhinitis. Ponies were significantly less likely to survive than cob types.
Wales AD, Whitwell KE.Two samples were taken postmortem from the rectum of each of 14 horses with grass sickness and 10 control horses, and four sections stained with haematoxylin and eosin were examined. By using as a criterion of grass sickness the presence of three chromatolytic neurons, 10 of the 14 cases were positive and none of the control horses was positive, giving a sensitivity of 71 per cent and a specificity of 100 per cent. No other histological features appeared to be of diagnostic value, and staining for Nissl substance in neurons with cresyl fast violet and methyl green-pyronin did not improve the s...
Wright A, Beard L, Bawa B, Bras J.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.
Milne EM, Fintl C, Hudson NP, Pearson GT, Mayhew IG, Hahn CN.This paper describes the histopathological and immunohistochemical changes in the central, autonomic and enteric nervous systems in a well-documented case of equine dysautonomia (ED), after the animal had recovered without significant residual clinical signs. Evidence of neuronal degeneration, such as neuronal chromatolysis, glial scars or a decrease in density of neurons, was not observed in the midbrain, pons, medulla oblongata or spinal cord, including the nuclei of cranial nerves III, V, VII, X and XII. In addition, no evidence of muscle denervation or re-innervation, such as group atrophy...
Wylie CE, Shaw DJ, Fordyce FM, Lilly A, McGorum BC.Equine grass sickness (EGS) remains a frequently fatal disease of equids in Britain. Since previous investigations of signalment- and meteorology-related risk factors for EGS have yielded some conflicting data, further investigation is warranted. Objective: To identify signalment- and meteorology-related risk factors for EGS in Scotland. Methods: Retrospective time-matched case-control study. Methods: This study was undertaken using data for 455 EGS cases and 910 time-matched controls that were referred to the Royal (Dick) School of Veterinary Studies, and average UK Meteorological Office weat...
Goren G, Fritz J, Dillitzer N, Hipp B, Kienzle E.Hay stabilises urine pH in horses. It is unknown whether this is an effect of structure or of chemical composition. In this study, four ponies (230-384 kg body weight [BW]) were fed six different diets with either a structure or a composition similar to hay with and without acidifiers in a cross-over experimental design in amounts to maintain body weight with the following main compounds: Fresh grass (GRASS), alfalfa hay (ALF), grass cobs (COBS), grass silage (SIL), straw (STR) or extruded straw (STRe) for 2 to 10 days. Urine pH was measured in all trials, blood pH, blood base excess and bicar...
Randleff-Rasmussen PK, Leblond A, Cappelle J, Bontemps J, Belluco S, Popoff MR, Marcillaud-Pitel C, Tapprest J, Tritz P, Desjardins I.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 s...
Bishop AE, Hodson NP, Major JH, Probert L, Yeats J, Edwards GB, Wright JA, Bloom SR, Polak JM.In recent years, distinct changes in regulatory peptides have been found in a number of gastrointestinal diseases. Grass sickness is a fatal disease of horses for which the etiology has yet to be fully ascertained. In this study, the peptide-containing nerves and ganglionic and mucosal endocrine cells of the ileum, colon and rectum were investigated in horses with sub-acute or chronic grass sickness and compared with normal controls using immunocytochemistry, at both the light and electron microscopical levels, and radioimmunoassay. A substantial loss of both peptide-containing cells and nerve...
McGorum BC, Wilson R, Pirie RS, Mayhew IG, Kaur H, Aruoma OI.The aetiopathogenesis of equine grass sickness (EGS) is unknown. The role of free radical-mediated neuronal damage has not previously been investigated in this condition. Objective: To investigate the potential contribution of oxidative damage and antioxidant status to neurodegeneration in EGS. Methods: Systemic levels of surrogate biomarkers were determined in 10 horses with acute EGS and in 2 control populations; 10 healthy horses co-grazing with the 10 EGS horses at the onset of clinical disease, and 10 healthy mares grazing where EGS has not been reported. Results: EGS horses had alteratio...
Jago RC, Handel I, Hahn CN, Pirie RS, Keen JA, Waggett BE, McGorum BC.Objective criteria for predicting survival of chronic grass sickness cases are currently lacking. Objective: To determine whether the rate and/or magnitude of bodyweight change during hospitalisation of chronic grass sickness cases can provide an objective predictor of survival to discharge from hospital. Clinicians' recorded indication(s) for euthanasia were also reviewed. Methods: Single centre retrospective observational study. Methods: Case records of all horses admitted for management of chronic grass sickness to The Dick Vet Equine Hospital between 1998 and 2013 were analysed. Case backg...
Ireland JL, McGorum BC, Proudman CJ, Newton JR.Without an experimental model of equine grass sickness (EGS), a randomised controlled field trial (RCT) represents the only method of evaluating the efficacy of Clostridium botulinum type C vaccination in preventing naturally occurring disease. Clinical trial feasibility is an important aspect of preliminary work undertaken prior to initiating RCTs, estimating parameters that are important for study design. This cross-sectional study aimed to assess the feasibility of conducting a nationwide RCT of a candidate vaccine for EGS based on responses from a sample of British equine veterinary practi...
Murray A, Cottrell DF, Woodman MP.Equine grass sickness (EGS) is a pan-dysautonomia of horses that involves central and peripheral neuronal degeneration and ultimately depletion. This is the first reported functional study on the motility of equine intestine taken immediately post mortem from horses with EGS. Strips of smooth muscle from the small intestine of healthy and EGS-affected horses were suspended in an organ bath and their motility was measured isometrically. The activity of the cholinergic system was studied. Physostigmine enhanced the motility of all muscle strips. Tissues taken from horses suffering from acute gra...
John HA, Marrs J, Laffling AJ.In the autonomic nervous system (ANS) of equine grass sickness (GS) cases, some neurones show abnormal changes while neighbouring neurones are unaffected. To test whether noradrenergic neurones showed variable susceptibility to the GS toxin in culture, clonally-derived populations isolated from the same fetal thoracic sympathetic chain ganglion were challenged with plasma from GS cases previously shown to induce ANS damage when injected into normal horses. During the early stages of exposure to toxic plasma, cells within a clonal population showed variable susceptibility ranging from no obviou...
Hunter LC, Poxton IR.The aetiology of equine grass sickness (EGS) is still unknown. There is increasing evidence that toxicoinfection with Clostridium botulinum type C is involved. Epidemiological evidence shows that resistance to EGS can occur in older horses and those that have been on a particular pasture for longer or have been in prior contact with the disease. This resistance may be in the form of an immune response to the aetiological agent. Levels of systemic antibodies to the surface antigens of C. botulinum type C (using the closely related and safe C. novyi type A as a phenotypic marker) and to the botu...
Shotton HR, Lincoln J, McGorum BC.Acute equine grass sickness (EGS) is a fatal disease of horses that is thought to be due to ingestion of a neurotoxic agent causing extensive damage to autonomic neurons. The aim of this study was to compare the effects of EGS on neurons in two sympathetic ganglia, the paravertebral cranial cervical ganglion (CCG) and the prevertebral coeliac/cranial mesenteric ganglion (CG/CMG). Specimens from horses with EGS and controls were obtained post mortem and processed using single and double immunofluorescence labelling for PGP 9.5 and HuC/HuD (pan-neuronal markers), TUNEL and caspase 3 (markers for...
Hedderson EJ, Newton JR.Their is both historical and modern scientific evidence to support the hypothesis that equine grass sickness (EC'S) is caused by a toxico-infectious form of botulism involving a Clostridium botulism type C toxin 1114 is produced locally within the gastrointestinal tract of affected horses (Toc her et al. 1923: Tneher 1924: Hunter a aL 1999: Hunter and anion 2001: McCarthy 2002: McCarthy a aL 201)4a1. This report concerns a meeting convened to review the current state of knowledge and possible strategies for vaccination against EGS. including historical. clinical and pathological aspects of the...
Pemberton AD, Hodgson JC, Gilmour JS, Doxey DL.Isolates were prepared from the sera of 12 horses with acute grass sickness, using methods reported to yield serum fractions associated with neurotoxicity, and their components identified by liquid chromatography and spectroscopy. All isolates were found to contain cortisol and six isolates also contained a degradation product of an analgesic drug, dipyrone. However, no recognised neurotoxin was detected.
Doxey DL, Milne EM, Gilmour JS, Pogson DM.An attempt has been made to assess the diagnostic value of clinical features seen at initial examination of horses with grass sickness, colic cases and cases submitted as possible grass sickness but diagnosed subsequently as some other condition. There appears to be no single pathognomonic sign for grass sickness. A range of signs has been associated with grass sickness but these are of value only when related to the length of illness and the history. Biochemical tests related to intestinal tissue damage, stress and dehydration were evaluated and most were found to be of value in diagnosing ac...
