History

A 12-year-old American Paint mare in late gestation (at approx 280 days of pregnancy) was evaluated because of unremitting mild to moderate colic of at least 36 hours' duration. The mare had been treated in the field with IV fluid therapy, flunixin meglumine administered IV, and mineral oil and water administered via nasogastric tubing without notable improvement. The horse was referred to the University of Georgia Veterinary Teaching Hospital for evaluation.

Clinical and Gross Findings

At the referral evaluation, the horse's heart rate was 100 beats/min, its extremities were cool to the touch, and its jugular filling times were prolonged. A dark red to purple band was seen across the alveolar gingiva (toxic gum line). A CBC revealed leucopenia (2,600 WBCs/μL; reference interval, 5,500 to 12,500 WBCs/μL) and hemoconcentration (Hct, 56.7%; reference interval, 32.0% to 52.0%). On abdominal ultrasonographic examination, there were fluid-distended loops of small intestine; mild signs of pain were elicited during the examination despite adequate sedation of the horse with butorphanol tartrate, ketamine hydrochloride, and diazepam. Owing to the lack of a definitive diagnosis, questionable prognosis, and financial constraints, the owners elected euthanasia by means of IV administration of barbiturate solution.

At necropsy, the small intestines and colon were dilated by abundant light brown and watery ingesta (Figure 1), consistent with the ultrasonographic findings. The wall of the cecum was diffusely edematous. No parasites were observed along the gastrointestinal tract.

View Full Size

Photograph of the small intestine of a 12-year-old American Paint mare in late gestation that was evaluated because of unremitting mild to moderate colic of at least 36 hours' duration. Notice that the small intestine is dilated by abundant gas and watery ingesta. The fluid lines indicate a large amount of fluid contents in the lumen.

Citation: Journal of the American Veterinary Medical Association 252, 6; 10.2460/javma.252.6.659

• Download Figure
• Download figure as PowerPoint slide

The lungs were diffusely dark red, and cut surfaces oozed large amounts of serosanguineous fluid. Ecchymoses were present on the costal pleura and throughout the peritoneal fat. Large areas of hemorrhage were present at the corticomedullary junctions of the adrenal glands.

The uterus contained a single large female foal. The foal, placenta, and uterus were grossly normal.

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→

Histopathologic Findings and Additional Laboratory Testing

Within the cecal wall, numerous macrophages, fewer plasma cells, and aggregates of neutrophils infiltrated the myenteric plexus and extended into the interganglionic nerve fibers and the epimysium and perimysium of adjacent smooth muscle bundles, admixed with edema and cellular debris (Figure 2). There were fewer ganglion cell bodies within the foci of inflammation, and the submucosa was diffusely expanded by edema and fibrin, with marked congestion of the submucosa and perivascular hemorrhage. The submucosal plexuses were unaffected. Many myocytes of the outer longitudinal muscular layer were degenerated, with hypereosinophilic and shrunken cytoplasm and pyknotic or absent nuclei. The inner circular muscular layer was not as severely affected. Similar but less severe changes were present in the colon and small intestine.

View Full Size

Photomicrographs of sections of the colon, centered on the myenteric plexus, of the horse in Figure 1 (A) and an unaffected 14-year-old Palomino gelding (B). The myenteric plexus of the horse in Figure 1 is hypercellular. H&E stain; bar = 200 μm. Inset—The myenteric plexus contains clusters of macrophages and fewer lymphocytes, plasma cells, and neutrophils admixed with necrotic debris, fibrin, and edema. Low numbers of ganglion cell bodies are present. H&E stain; bar = 50 μm. B—A section (available from an unrelated case) of the myenteric plexus of an unaffected horse is provided for comparison. Notice the prominent presence of intact ganglion cell bodies and the absence of inflammatory cells. H&E stain; bar = 200 μm. Inset—Ganglion cell bodies are intact in the myenteric plexus, and inflammation is absent. H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 252, 6; 10.2460/javma.252.6.659

• Download Figure
• Download figure as PowerPoint slide

In addition to routine histologic examination, a PCR assay and fluorescent antibody testing for equine herpesvirus-1 (EHV-1) were performed on pooled samples of the small intestine and colon. Results of both tests were negative. In addition, a McMaster fecal examination was performed, and no parasite ova were seen.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: marked, subacute, diffuse histiocytic and lymphocytic myenteric ganglioneuritis with ganglion cell loss and degeneration of the tunica muscularis in the cecum, colon, and small intestine.

Case summary: idiopathic or immune-mediated myenteric ganglioneuritis in a horse.

Comments

The enteric nervous system throughout the entire length of the gastrointestinal tract of horses is composed of 2 types of intramural nerve plexuses, namely the myenteric (Auerbach) plexus and the submucosal (Meissner) plexus. The myenteric plexus is located between the outer longitudinal muscular layer and the inner circular muscular layer of the gastrointestinal tract wall, whereas the submucosal plexus is located between the submucosa and circular muscular layer. The enteric nervous system acts in concert along with smooth muscle cells and interstitial cells of Cajal to coordinate movement of contents through the gastrointestinal tract.

Myenteric ganglioneuritis is an uncommon disease, and there are few reported cases in horses.^1–5 Histologically, myenteric ganglioneuritis is characterized by moderate to large numbers of inflammatory cells and decreased numbers of ganglia and ganglion cells in the myenteric plexus throughout the gastrointestinal tract. Myenteric ganglioneuritis is known to develop in birds, humans, and horses. In avian species, bornavirus infection is strongly implicated in proventricular dilatation disease, in which inflammation of the gastrointestinal ganglia leads to marked defects in digestive motility and results in dilation of the gastrointestinal tract.⁶ In the human medical literature, there are several reported cases of infections with herpesviruses that were associated with myenteric ganglioneuritis.⁷

The cause for equine myenteric ganglioneuritis is generally unknown. In 1 case, infection with EHV-1 was strongly implicated because the colonic wall was positive for EHV-1 (as determined by PCR assay) and enteroglial cells, lymphocytes, and endothelial cells were strongly positive for EHV-1 antigen (determined by immunohistochemical analysis).¹ No evidence of EHV-1 was found in normal latency tissues such as lymph nodes.¹ In another series of equine myenteric ganglioneuritis cases, concurrent infection with the tapeworm Anoplocephala perfoliata was investigated.³ Horses with A perfoliata infection had fewer myenteric ganglia and neuronal cells as well as increased chromatolysis and neuronal necrosis, compared with findings for control horses without A perfoliata infection.³ The inflammatory infiltrates in horses with A perfoliata infection were composed of lymphocytes, plasma cells, and eosinophils, similar to findings for the horse of the present report. On the other hand, eosinophils are not a prominent feature in reported cases of EHV-1 infection.

Equine dysautonomia (grass sickness disease) is characterized by widespread degeneration of the enteric autonomic system.⁴ Acute lesions include marked distension of the stomach and small intestine and impaction of the large intestine. Both submucosal and myenteric plexuses are generally involved in animals affected by equine dysautonomia.⁴ In contrast, both small and large intestines were fluid-dilated and only the myenteric plexus was affected in the horse of the present report. The typical clinical signs of equine dysautonomia including muscle fasciculations and patchy sweating were also absent in this horse.⁴ Therefore, equine dysautonomia was considered an unlikely differential diagnosis in this case.

Myenteric ganglionitis is often associated with intestinal pseudo-obstruction and impaction, presumably as a result of damage to and dysfunction of the autonomic nervous system and ileus. Diarrhea is an uncommon clinical sign but has been reported in a dog with myenteric ganglionitis; in that case, it was speculated that the diarrhea was attributable to extreme intestinal hypermotility subsequent to autonomic nervous system dysfunction.⁸ In humans with chronic intestinal pseudo-obstruction, diarrhea and steatorrhea have been attributed to bacterial overgrowth in the small intestine.⁹ It is unknown whether a similar mechanism occurs in horses.

Although fluorescent antibody testing and PCR assay failed to demonstrate the presence of EHV-1 in the horse of the present report, an underlying viral infection (eg, West Nile virus or bornavirus infection) could not be completely ruled out as a cause of the ganglioneuritis. No other diagnostic testing was performed; hence, a presumptive diagnosis of idiopathic or immune-mediated myenteric ganglioneuritis was made for this horse.