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     

In vitro response to noradrenaline of small intestine taken from normal and grass sickness-affected horses

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°C.In control tissue, noradrenaline produced contractions of muscle strips which did not involve a muscarinic cholinergic mechanism and which were unaffected by the 1 antagonist prazosin but were blocked by the 2 antagonist yohimbine. Pretreatment with the antagonist phentolamine prevented the contractile response to noradrenaline and the background contractions either continued at a reduced rate and amplitude or were abolished after a few minutes. Thus, following blockade, noradrenaline reduced the background contraction rate by an effect on inhibitory adrenoceptors. The rate of background contractions in duodenal preparations was significantly greater than that in control ileal preparations.Although cold storage for 24 h caused a reduction in the background contraction rates of the control preparations, there was no effect on the contractile responses to noradrenaline, the associated pharmacology being similar to that of fresh tissue. This suggests that noradrenaline-evoked contraction was not dependent on enteric neural elements.The response to noradrenaline by grass sickness-affected tissue was generally similar to that of tissue from control horses, with an immediate contraction which was 2 sensitive. The contractile response to noradrenaline after propranolol was significantly reduced in the CGS group and there were significant differences between the AGS, CGS and control groups. There was a significant difference between the ileal preparations from the control and SAGS groups in their response to noradrenaline following pretreatment with propranolol.     

Equine grass sickness

Equine grass sickness (EGS; equine dysautonomia) is a polyneuronopathy affecting both the central and the peripheral nervous systems of horses. As the name implies, EGS almost exclusively affects grazing horses, resulting in the development of a characteristic array of clinical signs, most of which can be attributed to neuronal degeneration in the autonomic and enteric nervous systems. Varying disease severities occur, largely determined by the extent of neuronal degeneration in the myenteric and submucous plexuses of the enteric nervous system. Extensive neuronal degeneration, as seen in acute and subacute forms of EGS, results in intestinal dysmotility, the severity of which is incompatible with survival. In comparison, a proportion of chronic forms of EGS, characterised by less severe neuronal degeneration, will survive. Despite extensive research efforts since EGS was first reported over 100 years ago, the precise aetiology remains elusive. This article reviews much of the scientific literature on EGS, covering epidemiology, pathology, diagnosis, treatment and aetiological hypotheses.     

Cholinergic activity of intestinal musclein vitro taken from horses with and without equine grass sickness

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 immediatelypost 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 grass sickness (AGS) had the longest latency before a measurable response could be obtained (p<0.05). The ileum appeared to be damaged by EGS to a greater extent than the duodenum. For the duodenal strips the enhanced rate of spontaneous contractions was significant (p<0.05) for both normal tissue and that affected by grass sickness but this was not the case for the ileal strips. Muscarinic receptor sensitivity investigation using bethanecol suggested a hypersensitivity of receptors with AGS material,Abbreviations AGS acute grass sickness - CGS chronic grass sickness - ED₅₀ median effective dose - EGS equine grass sickness - VIP vasoactive intestinal peptide     

Successful treatment of chronic grass sickness in a donkey

This case report outlines the successful management of a case of chronic grass sickness in a donkey and highlights that the occurrence of grass sickness may be underestimated in this species. Furthermore, grass sickness should be considered in the differential diagnosis in cases of inappetance and ill thrift in donkeys.     

Quantification of cyanogenic glycosides in white clover (Trifolium repens L.) from horse pastures in relation to equine grass sickness

As a preliminary step in testing the hypothesis that ingestion of cyanogenic glycosides in white clover (Trifolium repens L.) may be one of the risk factors for equine grass sickness (EGS, or equine dysautonomia), the cyanogen content of clover leaves collected from fields (n = 16) soon after an occurrence of EGS was compared with that of (i) control white clover samples (n = 10) collected from the same fields out of the disease period and (ii) control clover samples (n = 54) collected sequentially from three control fields. Clover samples from EGS fields were highly cyanogenic, with a median cyanide potential of 497 (range 307–1786) mg kg dry matter^?1. Furthermore, clover collected from EGS fields soon after an occurrence of EGS had significantly higher concentrations of the cyanogenic glycosides linamarin and lotaustralin than control samples. While these findings indicate that horses grazing EGS fields may ingest significant quantities of cyanogenic glycosides, the design of the study does not facilitate investigation of any potential association between cyanogens and EGS. Further study is therefore required to determine whether cyanogens are a risk factor for EGS or whether these findings simply reflect variations in plant metabolism unrelated to disease pathogenesis.     

An acute outbreak of equine dysautonomia (equine grass sickness) in a group of eight Przewalski's horses (Equus ferus [caballus] przewalskii)

Equine grass sickness (EGS) is a neurodegenerative disease affecting grazing equids of which a single case of the chronic clinical presentation has previously been reported in a Przewalski's horse (Equus ferus [caballus] przewalskii). A group of 8 Przewalski's horses were moved to a new enclosure, recently vacated by a group of 4 Eastern kiang (Equus kiang holdereri) that showed no evidence of disease. After 23 days the first Przewalski's horse showed clinical signs of acute EGS including flank sweating, belly kicking, rapid loss of body condition, cessation of faecal passage, nasogastric reflux and mouthing water. It was subjected to euthanasia within 48 h due to lack of therapeutic response. Within 24 h of this first case developing clinical signs, a further 5 Przewalski's horses showed similar clinical signs of acute EGS and were subjected to euthanasia. Post mortem examinations confirmed acute EGS, with all animals demonstrating typical chromatolysis, cytoplasmic hypereosinophilia, cellular swelling, vacuolation, pyknosis and loss of nuclei in approximately 90% of neurones in the cranial cervical and cranial mesenteric ganglia and myenteric and submucosal plexi of the ileum. Two Przewalski's horses within the group showed no clinical signs of disease. No single pathogen was identified as the causal agent, but the epidemiological pattern of the outbreak was typical for that previously reported for acute EGS in domestic equids. All affected animals and the 2 surviving Przewalski's horses had low antibody titres to Clostridium botulinum type C. This is the first report of acute EGS in a herd of Przewalski's horses.