Enteric neuron density correlates with clinical features of severe gut dysmotility.

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are mainly based on classic qualitative histopathological / immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to assess the myenteric inter-ganglionic distance, i.e. the micrometer between two adjacent clusters of myenteric neurons 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 years) with well-characterized severe dysmotility and 8 controls (4 females; 47-73 years). A symptom questionnaire was filled prior to surgery. Mann-Whitney U-test, Kruskal-Wallis coupled with Dunn's post-test and non-parametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared to controls, patients with severe dysmotility exhibited a significant increase in myenteric inter-ganglionic 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 inter-ganglionic 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 inter-ganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an inter-ganglionic distance within the control range.