Human enteric neuropathies: morphology and molecular pathology

Abstract

The aim of this study is to review current understanding of the molecular and morphological pathology of the enteric neuropathies affecting motor function of the human gastrointestinal tract and to evaluate the described pathological entities in the literature to assess whether a new nosology may be proposed. The authors used PUBMED and MEDLINE searches to explore the literature pertinent to the molecular events and pathology of gastrointestinal motility disorders including achalasia, gastroparesis, intestinal pseudo-obstruction, colonic inertia and megacolon in order to characterize the disorders attributable to enteric gut neuropathies. This scholarly review has shown that the pathological features are not readily associated with clinical features, making it difficult for a patient to be classified into any specific category. Individual patients may manifest more than one of the morphological and molecular abnormalities that include: aganglionosis, neuronal intranuclear inclusions and apoptosis, neural degeneration, intestinal neuronal dysplasia, neuronal hyperplasia and ganglioneuromas, mitochondrial dysfunction (syndromic and non-syndromic), inflammatory neuropathies (caused by cellular or humoral immune mechanisms), neurotransmitter diseases and interstitial cell pathology. The pathology of enteric neuropathies requires further study before an effective nosology can be proposed. Carefully studied individual cases and small series provide the basic framework for standardizing the collection and histological evaluation of tissue obtained from such patients. Combined clinical and histopathological studies may facilitate the translation of basic science to the clinical management of patients with enteric neuropathies.

Chronic Intestinal Pseudo-Obstruction due to Buserelin-Induced Formation of Anti-GnRH Antibodies

“…Due to the clinical picture and the findings of antroduodenojejunal manometry and histopathological analysis, the patient fulfils the criteria for CIPO (12)(13)(14). The sudden onset of this disease in a previously seemingly healthy young woman puzzled us.…”

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

“…Cells in ENS are organized as two major plexuses, the myenteric and the submucous plexus, and their main function is to control most of the gastrointestinal functions (33) . Among these functions, we can mention the regulation of enteroendocrine and paracrine secretion, absorption of nutrients and fluids, vascular tone, sensorial information and motility (6,11,14) . Several studies have reported degenerative characteristics in the nervous tissue of the gastrointestinal tract caused by diseases that affect the digestive canal or the ENS itself.…”

Enteric Autoantibodies and Gut Motility Disorders

“…The typical finding is a dense plasma cell and lymphocytic infiltrate in and around the ganglia. The identity of the lymphocytic infiltrate (CD3 positive and both CD4 and CD8 positive cells) suggests a T-cell mediated injury to the ganglionic cells, although B-cells have also been reported [37,38]. Myenteric ganglia are invariably involved however submucosal ganglia may also sometimes be involved.…”

“…Most cases of chronic intestinal pseudoobstruction are due to primary defects in the contractile apparatus (nerves, interstitial cells of Cajal, smooth muscle cells) of the gut or secondary to an infiltrating disease such as amyloidosis or scleroderma [37][38][39]. Paraneoplastic intestinal pseudoobstruction is most often reported in cases with small cell lung cancer and thymoma and is usually associated with the presence of circulating ANNA-1 antibodies [40][41][42][43][44].…”