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

Abstract

BACKGROUND: Equine dysautonomia (ED) causes degeneration and loss of autonomic neurons. Approximately 50% of chronic cases recover, but it is unclear how they survive neuronal loss. OBJECTIVES: To assess lesions, autonomic neuron numbers, interstitial cells of Cajal (ICC), and neurodegeneration in recovered cases. ANIMALS: Thirteen cases (group ED), euthanized 10.3&#x2009;&#xb1;&#x2009;5.2 (1-16) years from diagnosis and 6 age-matched controls (group C). METHODS: Prospective, case control; routine post mortem examination, neuron counts in peripheral and enteric ganglia and immunohistochemical assessment of neural networks (Protein gene product [PGP] 9.5), ICC (c-kit), and neurodegeneration (beta-amyloid precursor protein and ubiquitin) in intestine. RESULTS: Postmortem findings in group ED were small intestinal dilation (4/12, 33%) and muscular hypertrophy (4/12, 33%), and gastric mucosal hypertrophy (3/11, 27%) and ulceration (4/11, 36%). Neuron density was lower in group ED (mean 39% lower for cranial cervical ganglion [P <&#x2009;.001], median 44% lower in celiacomesenteric ganglion [P =&#x2009;.01]). In intestine, neuronal depletion was worst in ileum (median 100% lower in submucosal plexus [P <&#x2009;.001], 91% lower in myenteric plexus [P =&#x2009;.004]). Group ED had less PGP 9.5 staining in ileal myenteric plexus (mean 66% lower [P =&#x2009;.04]) and circular muscle (median 75% lower [P =&#x2009;.006]). In ileum, there was less c-kit staining in myenteric plexus (median 57% lower [P =&#x2009;.02]) but not muscularis externa. Beta-amyloid precursor protein and ubiquitin results were not indicitive of neurodegeneration. CONCLUSIONS AND CLINICAL IMPORTANCE: Intact ICC in muscularis externa might help maintain motility after neuronal loss. Treatment supporting ICC function warrants investigation.