Residual Lesions Study

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

Elspeth M. Milne, R. Scott Pirie, Caroline N. Hahn, Jorge del-Pozo, Dawn Drummond, Sharon Moss, Bruce C. McGorum. Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Easter Bush Campus, Roslin, Midlothian, EH25 9RG, United Kingdom

Background: Equine dysautonomia (ED) causes degeneration and loss of nerve cells (neurons) in parts of the nervous system that control involuntary functions (autonomic nervous system) e.g. intestinal activity. Approximately 50% of chronic cases recover, but it is unclear how they survive the loss of neurons. The network of interstitial cells of Cajal (ICC) in the wall of the intestine are known to have a “pacemaker” function and in a single previously studied recovered case, an intact network of ICC was found.

Objectives: To assess pathology, autonomic neuron numbers, ICC and degenerative changes in neurons in recovered cases of ED.

Animals: Thirteen horses (group ED), euthanized an average of 10 (range 1-16) years from diagnosis and 6 age-matched controls (group C) euthanized for reasons not connected with the digestive tract or nervous system were studied. All sampling was carried out post mortem and with the owners’ consent, and all samples were anonymized for analysis and publication. Horses in both groups were euthanized for welfare reasons and not purely for the study.

Methods: Post mortem findings, neuron counts in microscopic sections of intestinal wall and autonomic ganglia (nerve “junction boxes”) and special stains on microscopic sections for ICC and degeneration of neurons in four intestinal sites (two in the small intestine and two in the large intestine).

Results: Post mortem findings in group ED were small intestinal dilation (33% of cases), small intestinal muscle wall thickening (33%), stomach lining thickening (27%) and stomach ulcers (36%). Such changes were not seen in group C. Neuron numbers in the autonomic ganglia were significantly lower in group ED (39% lower than group C for cranial cervical ganglion and 44% lower in coeliacomesenteric ganglion). In intestine, loss of neurons was worst in the last part of the small intestine (ileum) (100% lower than group C in the neuron groups under the intestinal lining and 91% lower in the neuron groups between the muscle layers of the wall of the ileum). In ileum and jejunum (mid-small intestine), the ICC networks were not significantly different in the muscle wall of group ED in comparison with group C. Special stains to identify active degeneration of neurons did not provide evidence for ongoing degeneration. The large intestine was almost unaffected for all aspects studied.

Conclusions and clinical importance: Post mortem findings suggested that some horses have short and long-term changes in the stomach and small intestine years after recovery from clinical signs of ED. They can also survive for many years in the presence of severe loss of neurons in the autonomic nervous system, especially the ileum. Intact ICC in the muscle wall of the small intestine may help maintain intestinal propulsive activity in the long term after loss of neurons. Development of therapy supporting ICC function therefore warrants investigation.

Acknowledgements: The authors thank the Equine Grass Sickness Fund for generous financial support and for publicising the study to horse owners. The authors are also grateful to the owners, primary clinicians, and the staff of the Dick Vet Equine Hospital and Pathology Department for their invaluable help. In particular, the study could not have been undertaken without owners’ help.

Full article reference: Journal of Veterinary Internal Medicine DOI10.111/jvim.15567 and also available on the Equine Grass Sickness Fund website https://grasssickness.org.uk