Enteric neuron density correlates with clinical features of severe gut dysmotility

Abstract

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are based mainly on classic qualitative histopathological/immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to quantify the interganglionic distance between neighboring myenteric ganglia immunoreactive for neuron-specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies/ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16–77 yr) with well-characterized severe dysmotility and 8 controls (4 females; 47–73 yr). A symptom questionnaire was filled before surgery. Mann-Whitney U test, Kruskal-Wallis coupled with Dunn’s posttest and nonparametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared with controls, patients with severe dysmotility exhibited a significant increase in myenteric interganglionic distance ( P = 0.0005) along with a decrease in the number of myenteric ( P < 0.00001) and submucosal ( P < 0.0004) neurons. A 50% reduction in the number of submucosal and myenteric neurons correlated with an increased interganglionic distance and severity of dysmotility. Our study proposes a relatively simple tool that can be applied for quantitative evaluation of paraffin sections from patients with severe dysmotility. The finding of an increased interganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an interganglionic distance within the control range. NEW & NOTEWORTHY Enteric neuropathies are challenging conditions characterized by a severe impairment of gut physiology, including motility. An accurate, unambiguous assessment of enteric neurons provided by quantitative analysis of routine paraffin sections may help to define neuropathy-related gut dysmotility. We showed that patients with severe gut dysmotility exhibited an increased interganglionic distance associated with a decreased number of myenteric and submucosal neurons, which correlated with symptoms and clinical manifestations of deranged intestinal motility.

Clinical and Histopathological Spectrum of Adult Gastrointestinal Inflammatory Neuropathy

“…The mortality in CIPO is often attributed to the intestinal failure and leakiness of the gut owing to the abnormalities of intestinal epithelial and vascular barrier. 17 One of our cases succumbed to the illness due to septicemia and we believe a similar etiopathogenesis in the index case.…”

The enteric nervous system in gastrointestinal disease etiology

“…Additionally, CIPO has been reported in patients with autosomal dominant mutations in the SOX10 gene in Waardenburg-Shah syndrome [ 90 ], and is also related to sex chromosome inheritance in Xq28 with mutations in Filamin A and L1CAM genes [ 91 , 92 ]. Although abnormalities in gastrointestinal motility in patients with CIPO manifest in the presence of enteric ganglia [ 85 ], a neuronal deficit of approximately 50% associated with increased distance between ganglia, neuronal swelling and axonal degeneration and which correlates with the degree of symptom severity has been reported [ 93 ]. This is also the case for slow transit constipation, defined by reduced and infrequent intestinal transit, sensation of anorectal obstruction and solid fecal content [ 94 ].…”

Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives

“…In a recent study, jejunal full-thickness biopsies were collected from patients suffering from severe gut dysmotility, either by laparoscopy or by conventional abdominal laparotomy. By quantifying the inter-ganglionic distance between neighboring myenteric ganglia and the number of neurons per ganglion in the myenteric and submucosal plexus, the authors showed that patients with enteric dysmotility had significantly fewer myenteric and submucosal neurons [ 140 ]. The methodology has been refined, and a new technique has utilized the evaluation of standard submucosal biopsies.…”