Neurodegeneration and Neuroplasticity of the Intrinsic Innervation of the Gut in Severe Dysmotility

Abstract

Abnormalities in the gastrointestinal neuromuscular apparatus including interstitial cells of Cajal (ICC) is presumed to underlie a clinically heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). A subset of these patients may manifest clinically with recurrent intestinal sub-occlusive episodes, which occur in the absence of demonstrable mechanical causes, leading to numerous hospitalizations as well as useless and potentially harmful surgical interventions. Taken together clinical and radiological signs make up a condition referred to as chronic intestinal pseudo-obstruction (CIPO). This is a rare and intractable chronic digestive disease that can result from abnormalities of smooth muscle cells (effectors of contractility / relaxation), ICC (pace-makers of gut motility and regulators of neuronal input to smooth muscle cells), and neurons (either intrinsic – the enteric nervous system- or extrinsic nerve pathways). The present thesis was thought to provide a translational view by characterizing dysmotility and establishing attendant histopathological defects in CIPO and determine whether a correlation exists between clinical features, motility patterns and neuromuscular changes, using qualitative and quantitative morphological approaches. In this thesis I provided an update on neurointestinal diseases, with special focus on diagnostic, therapeutic and management aspects of CIPO, which have been published during the PhD course. My senior dissertation deals with major neurogastroenterological aspects, such as those involving the most severe forms of the functional GI disorder spectrum, i.e. those patients with prominent abnormalities of gut propulsion. A better understanding of these cases will cast hope about patient management and newly applicable therapeutic intervention.