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.
Cottrell DF, McGorum BC, Pearson GT.Autonomic dysfunction constitutes a prominent clinical feature of equine grass sickness (EGS). Significant injury to the nervous control of the alimentary system is life threatening, partly because of dysphagia but also because of the failure of the unique regulatory mechanisms in equine digestion involving water and electrolyte balance. The neuropathology also indicates the presence of a somatic polyneuropathy. The morphological features of EGS are similar to those of excitotoxic neuronal degeneration, which resembles neuronal apoptosis. It is difficult to ascertain from published accounts th...
Wood JL, Milne EM, Doxey DL.A case-control study was performed to investigate the epidemiology of grass sickness in the United Kingdom from 1992 to 1995. Data were collected by means of postal questionnaire when cases of grass sickness were identified. Sets of three questionnaires were posted to owners of, or veterinary surgeons attending, cases of grass sickness, with a request to provide information on the case, on one healthy animal on the same premises as the case and on another healthy animal on other premises. Controls were matched to cases by date of onset. After univariate analyses, the probability of grass sickn...
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.
Murray A, Pearson GT, Cottrell DF.Small intestine was taken from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold of 25 horses, 9 with acute grass sickness (AGS), 12 with subacute grass sickness (SAGS) and 12 with chronic grass sickness (CGS). The motility in the samples was measured isometrically either within 1 h of death or after storage for 24 h at 4 degree C. In control tissue, noradrenaline produced contractions of muscle strips which did not involve a muscarinic cholinergic mechanism and which were unaffected by the alpha 1 antagonist prazosin but were blocked by the alpha 2 anta...
Mair TS, Hillyer MH.The clinical features of 106 horses presenting with chronic colic examined over a 5 year period were reviewed. Chronic colic was defined as colic signs observed daily for 3 days or longer, except when masked by analgesics. The diagnosed causes of chronic colic included colonic impaction (31%), peritonitis (16%), enteritis/colitis (7%), colonic displacement/torsion (6%) and lymphosarcoma (4%). A variety of other diseases were diagnosed in a small number of cases, including intestinal adhesions, ileal obstructions, grass sickness, liver disease, caecal impactions, thromboembolic disease, intussu...
Murray A, Pearson GT, Cottrell DF.Light microscopy was undertaken on sections from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold in 5 control horses, 5 horses with acute grass sickness (AGS), and 5 horses with chronic grass sickness (CGS). With the exception of the ileal submucous plexus of the CGS group, the AGS group had the lowest number of neurons as measured using a subjective scoring scheme. The proportion of abnormal neurons in the AGS group was similar in both plexuses and both regions, whereas the values for the CGS group were much higher in the duodenal region than in the i...
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 ...
Uzal FA, Woodman MP, Giraudo CG, Robles CA, Doxey DL.'Mal seco' is an almost invariably fatal disease of horses in Argentina and Chile, which resembles grass sickness, a dysautonomia of horses in Europe. The aetiology of mal seco remains unknown. An attempt to reproduce the disease was made by feeding horses with Festuca argentina, a plant considered to be toxic to animals and which was consistently found in the diet of nine horses suffering from mal seco. Three horses were fed with F argentina ad libitum for 28 days. The plant was infected with an endophytic fungus, whose morphological characteristics were in agreement with descriptions of Acre...
Doxey DL, Milne EM, Harter A.The outcome for 35 horses with chronic dysautonomia which were kept in the hospital at the Royal (Dick) School of Veterinary Studies and subsequently returned to their owners is recorded. They constituted 42.7 per cent of the 82 chronic cases seen between 1991 and 1994; the other 47 horses were euthanased while in hospital. Of the 35 animals returned to their owners four died and 27 were available for follow up; of these 27, 12 were working competitively and six were being trained for future competitive work. It takes at least a year before it is clear whether a horse can compete successfully ...
Doxey DL, Tothill S, Milne EM, Davis Z.Three horses suffering from grass sickness were treated successfully but showed clinical signs which varied in severity and duration. They were all characterised by marked and often erratic changes in behaviour and appetite.
Doxey DL, Milne EM, Woodman MP, Gilmour JS, Chisholm HK.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 distribut...
Griffiths IR, Smith S, Doxey DL, Whitwell K, Love S.Sera from acute and chronic cases of natural grass sickness or normal horses were injected into the parotid salivary gland of ponies. This gland receives its sympathetic innervation from the ipsilateral cranial cervical ganglion. None of the ponies showed any local or systemic signs of illness. After one week the cranial cervical ganglia, stellate and coeliaco-mesenteric ganglia were removed for histological study. Pathological changes were found only in the cranial cervical ganglion ipsilateral to a parotid salivary gland which had received an injection of grass sickness serum. Four out of fi...
Gruys E, Beynen AC, Binkhorst GJ, van Dijk S, Koeman JP, Stolk P.The most important neurodegenerative diseases of the horse are reviewed. In addition to the literature, neurodegenerative diseases occurring in patients (horses, Mongolian Przewalski-horses, and two zebras) referred to the Utrecht Veterinary Faculty are mentioned. Neurodegenerative diseases described are: I. ataxia associated with: A/ static stenosis, B/ dynamic stenosis, C/ lesions at various locations in the central nervous system, D/ equine herpesvirus infections, E/ equine degenerative myelo-encephalopathy, or F/ cerebellar abiotrophy; II. equine motor neuron disease; III. grass sickness o...
Uzal FA, Doxey DL, Robles CA, Woodman MP, Milne EM."Mal seco" is a disease of unknown aetiology affecting horses in Argentina. It is similar to grass sickness, a primary dysautonomia of horses in Europe. A histopathological study of the brain stem nuclei of three horses with "mal seco" was performed. Changes were found that consisted of chromatolysis, cytoplasmic vacuoles, eosinophilic sphaeroids, and pyknotic and eccentric nuclei. These changes were most severe at the oculomotor, vestibular and abducent nuclei. The results provide further evidence to suggest that "mal seco" and grass sickness may be the same disease.
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.
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...
Griffiths IR, Kyriakides E, Smith S, Howie F, Deary AW.Equine grass sickness (EGS) is a primary dysautonomia characterised pathologically by lesions in autonomic ganglia, enteric plexi and specific nuclei in the CNS. Immunocytochemistry and lectin histochemistry of the autonomic ganglia were used to determine whether abnormalities can be detected in specific proteins or cellular organelles. EGS ganglia contained a mixture of morphologically normal and abnormal neurons, the former appearing identical to cells from control animals. Affected cells showed marked disturbances in neurofilament (NF) proteins and beta-tubulin, major components of the cyto...
Scholes SF, Vaillant C, Peacock P, Edwards GB, Kelly DF.Ileal biopsies were obtained from 18 horses with grass sickness, 15 horses with other alimentary disease and three horses without gastrointestinal disease. Samples of small intestine were also obtained from nine cases of obstruction due to small intestinal strangulation. Histological examination revealed that severe enteric neuropathy in the absence of other significant morphological changes was confined to the horses with grass sickness.
Scholes SF, Vaillant C, Peacock P, Edwards GB, Kelly DF.The degeneration of enteric neurones has been recorded in grass sickness, but the distribution of the lesions in the gut and their possible relationship with the severity of the clinical signs has not been established. Samples obtained from 11 anatomically defined sites along the gastrointestinal tract of eight control horses without gastrointestinal disease, five horses with acute grass sickness and three horses with chronic grass sickness were examined histologically. The organisation of the enteric ganglia was similar to that in other large mammalian species. Minor exceptions included the p...
Leendertse IP.A three year old warm-blood gelding with severe colic was referred to a veterinary clinic. The history revealed that the horse was found early in the morning with severe colic, and laying in the pasture. On arrival the clinical examination showed a complete wet horse with a pulse rate of 92/min, a respiratory rate of 24/min., a pcv of 0.50 L.L.-1, a T. of 38.0 degrees C, and no gastric reflux. Rectal examination revealed a sticky rectal mucous membrane and a colonic impaction together with displacement of the large colon. A diagnostic laparotomy showed an impaction as is seen in horses with Gr...
Pogson DM, Doxey DL, Gilmour JS, Milne EM, Chisholm HK.Histological investigations were undertaken on four sympathetic autonomic ganglia and on the myenteric and sub-mucosal plexuses of the jejunum in healthy animals, in naturally occurring cases of acute, sub-acute and chronic equine dysautonomia and in ponies in which neuronal damage had been induced by the injection of acute grass sickness sera. The degree of neuronal damage is related to the type of dysautonomia. The coeliac-mesenteric ganglion reacts differently from other ganglia and is less severely damaged in cases of short duration. Extensive experimentally induced damage to the coeliac-m...
Doxey DL, Pogson DM, Milne EM, Gilmour JS, Chisholm HK.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 an...
Uzal FA, Robles CA, Olaechea FV.'Mal seco' is a grass sickness-like syndrome of horses in Argentina. A histopathological study was made of the coeliaco-mesenteric ganglia of four horses with 'mal seco' and of four horses that died from other causes. The severity and extent of the lesions found in the horses with 'mal seco' was greatest in the two with the shortest clinical course. Degenerative changes consisted mainly in the loss of Nissl substance, cytoplasmic vacuoles, neuronophagia, intercellular and intracytoplasmic eosinophilic bodies, and pyknotic and eccentric nuclei. The coeliaco-mesenteric ganglia of the control hor...
Wright JA, Hodson NP.Lesions in a wide range of cranial nuclei are described in 11 horses with grass sickness. Similar changes were seen in one horse with laminitis, but not in control animals. It is suggested that such lesions are non-specific in nature.
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 ...
Johnson P.An unusual compound of small molecular weight has been detected in serum from horses with acute grass sickness by solvent extractions and thin-layer chromatography. The substance has not been detected in the serum of normal horses or cases of equine colic and apparently disappears from grass sickness serum after two to three days of clinical illness. Although this compound is found in sera which are known to possess in vivo neurotoxicity, this property could not be demonstrated in either the total chloroform extract which contains the compound or in the hydrophilic serum components remaining a...
Uzal FA, Woodman MP, Giraudo CG, Robles CA, Doxey DL.'Mal seco' is an almost invariably fatal disease of horses in Argentina and Chile, which resembles grass sickness, a dysautonomia of horses in Europe. The aetiology of mal seco remains unknown. An attempt to reproduce the disease was made by feeding horses with Festuca argentina, a plant considered to be toxic to animals and which was consistently found in the diet of nine horses suffering from mal seco. Three horses were fed with F argentina ad libitum for 28 days. The plant was infected with an endophytic fungus, whose morphological characteristics were in agreement with descriptions of Acre...
Kramer KJ, Kagan IA, Lawrence LM, Smith SR.Ethanol-soluble carbohydrates (ESCs) of cool-season grasses include mono- and disaccharides and sometimes short-chain fructans, which may exacerbate the risk of pasture-associated laminitis. A calibration for prediction of ESC concentrations by near-infrared reflectance spectroscopy (NIRS) was developed from 323 samples of four cool-season grass species (orchardgrass, Kentucky bluegrass, tall fescue, and perennial ryegrass) across 10 cultivars collected in central Kentucky in the morning and afternoon over two growing seasons. The calibration, which had accuracy above 95%, was used to predict ...
Griffiths IR, Smith S, Doxey DL, Whitwell K, Love S.Sera from acute and chronic cases of natural grass sickness or normal horses were injected into the parotid salivary gland of ponies. This gland receives its sympathetic innervation from the ipsilateral cranial cervical ganglion. None of the ponies showed any local or systemic signs of illness. After one week the cranial cervical ganglia, stellate and coeliaco-mesenteric ganglia were removed for histological study. Pathological changes were found only in the cranial cervical ganglion ipsilateral to a parotid salivary gland which had received an injection of grass sickness serum. Four out of fi...
Milne EM, Doxey DL, Gilmour JS.Serum total lipids, lipoprotein fractions, triglycerides, cholesterol, phospholipids and free fatty acids were measured in horses with acute, subacute and chronic grass sickness (equine dysautonomia) and in colic cases. The values were compared with those of normal grazing and stabled horses. A marked individual variation occurred, but total lipids, triglycerides and free fatty acids were significantly higher than normal in grass sickness and colic cases with cholesterol was significantly higher than normal in grass sickness cases only. Pre-beta lipoprotein was significantly increased in colic...
Stratford CH, Pemberton A, Cameron L, McGorum BC.Although a presumptive diagnosis of acute grass sickness (AGS) can be made on the basis of clinical signs, a definitive ante mortem diagnosis currently requires histological examination of enteric ganglia. Development of an accurate noninvasive ante mortem diagnostic test is therefore warranted. The objective of this study was to determine whether quantification of the plasma concentrations of the heavily phosphorylated form of major neurofilament subunit NF-H (pNF-H), which mirror the degree of axonal degeneration in some human and animal neurodegenerative disorders, could distinguish AGS-aff...
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...
Nunn FG, Pirie RS, McGorum B, Wernery U, Poxton IR.Serum from 12 horses suffering from chronic grass sickness (CGS) were assayed for IgG antibodies against botulinum neurotoxins C and D (BoNT/C and BoNT/D) and to a surface antigen extract of a neurotoxin negative strain of Clostridium botulinum type C. Collectively, the six surviving CGS cases demonstrated significantly higher initial IgG levels (P=0.05) against surface antigens than the six that were subsequently euthanased. The surviving animals also demonstrated higher initial IgG levels against the BoNT/C but not reaching significance (P=0.06). The two groups demonstrated no difference bet...
Laus F, Corsalini J, Mandara MT, Bazzano M, Bertoletti A, Gialletti R.Equine grass sickness (EGS) has been reported in several European and extra-European countries. Despite this, no scientific paper about clinical cases of EGS in Italy has been published. EGS is a disease affecting almost exclusively horses kept on pasture, characterized by clinical signs related to lesions in autonomic nervous system (ANS), particularly in the enteric nervous system (ENS). According to clinical presentation, acute, subacute and chornic syndromes can be observed, with various sympthoms including dullness, anorexia, dysphagia, drooling of saliva, tachycardia, ptosis, patchy swea...
Jago RC, Scholes S, Mair TS, Pearson GR, Pirie RS, Handel I, Milne EM, Coyle F, Mcgorum BC.An accurate, minimally invasive, ante-mortem diagnostic test for equine grass sickness (EGS) is currently lacking. Although histological examination of haematoxylin and eosin-stained rectal biopsies for chromatolytic neurons is insensitive as a diagnostic test for EGS, we hypothesised that its diagnostic accuracy could be improved by immunolabelling for β-amyloid precursor protein (β-APP), which has increased expression in cranial cervical ganglia (CCG) neuronal perikarya in EGS. Objective: To develop a grading scheme for assessing the distribution and intensity of β-APP immunoreactivity wi...
Murray A, Pearson GT, Cottrell DF.Small intestine was taken from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold of 25 horses, 9 with acute grass sickness (AGS), 12 with subacute grass sickness (SAGS) and 12 with chronic grass sickness (CGS). The motility in the samples was measured isometrically either within 1 h of death or after storage for 24 h at 4 degree C. In control tissue, noradrenaline produced contractions of muscle strips which did not involve a muscarinic cholinergic mechanism and which were unaffected by the alpha 1 antagonist prazosin but were blocked by the alpha 2 anta...
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...
Fintl C, Hudson NP.Gastrointestinal motility disorders are a serious problem in both veterinary and human medicine and may represent a dysfunction of the neural, muscular or pacemaker components (interstitial cells of Cajal) of bowel control. The interstitial cells of Cajal are considered to be the pacemakers and mediators of certain forms of neurotransmission in the gastrointestinal tract. These cells have been implicated, either primarily or secondarily, in the pathogenesis of gastrointestinal disease processes in which there is a prominent element of disturbance to intestinal motility. In the horse, their inv...
McGorum BC, Chen Z, Glendinning L, Gweon HS, Hunt L, Ivens A, Keen JA, Pirie RS, Taylor J, Wilkinson T, McLachlan G.Equine grass sickness (EGS) is a multiple systems neuropathy of grazing horses of unknown aetiology. An apparently identical disease occurs in cats, dogs, rabbits, hares, sheep, alpacas and llamas. Many of the risk factors for EGS are consistent with it being a pasture mycotoxicosis. To identify potential causal fungi, the gastrointestinal mycobiota of EGS horses were evaluated using targeted amplicon sequencing, and compared with those of two control groups. Samples were collected post mortem from up to 5 sites in the gastrointestinal tracts of EGS horses (EGS group; 150 samples from 54 horse...
Nunn FG, Pirie RS, McGorum B, Wernery U, Poxton IR.There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state. Objective: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract...
Uzal FA, Doxey DL, Robles CA, Woodman MP, Milne EM."Mal seco" is a disease of unknown aetiology affecting horses in Argentina. It is similar to grass sickness, a primary dysautonomia of horses in Europe. A histopathological study of the brain stem nuclei of three horses with "mal seco" was performed. Changes were found that consisted of chromatolysis, cytoplasmic vacuoles, eosinophilic sphaeroids, and pyknotic and eccentric nuclei. These changes were most severe at the oculomotor, vestibular and abducent nuclei. The results provide further evidence to suggest that "mal seco" and grass sickness may be the same disease.
Wylie CE, Shaw DJ, Fordyce FM, Lilly A, Pirie RS, McGorum BC.We hypothesised that the apparent geographical distribution of equine grass sickness (EGS) is partly attributable to suboptimal levels of soil macro- and trace elements in fields where EGS occurs. If proven, altering levels of particular elements could be used to reduce the risk of EGS. Objective: To determine whether the geographical distribution of EGS cases in eastern Scotland is associated with the presence or absence of particular environmental chemical elements. Methods: Retrospective time-matched case-control study. Methods: This study used data for 455 geo-referenced EGS cases and 910 ...
McGorum BC, Pirie RS, Shaw D, Macintyre N, Cox A.Diagnosis of equine grass sickness (EGS) can be challenging. We hypothesised that subgemmal plexus neurons are chromatolytic in EGS. If correct, histopathological examination of gustatory papillae biopsies could aid premortem diagnosis of EGS, and EGS could represent a spontaneous model of subgemmal neuronal chromatolysis to facilitate study of the pathology of structures involved in taste. Objective: To compare subgemmal plexi and gustatory papillae in EGS and control horses. Methods: Observational study. Methods: Conventional histology and immunohistochemistry were used to compare subgemmal ...
Michl J, Modarai M, Edwards S, Heinrich M.Identification of toxic or harmful agents continues to be a key goal in agricultural chemistry. This paper reports a metabolomic analysis of Ranunculus repens and related species, which were recently postulated to be cocausative agents in the etiology of equine grass sickness (EGS). Specifically, samples collected at EGS sites were compared with those from non-EGS sites. Furthermore, interspecific and seasonal variations and the species' response to edaphic and climatic factors were investigated. (1)H NMR spectroscopy in combination with multivariate data analysis was applied to the crude meth...
Hodson N, Hunt J, Causon RC.The research article discusses an investigation into how exploratory diagnostic laparotomy affects the circulating histamine levels in acute, subacute, and chronic suspected equine grass sickness cases. The study utilized a […]
