Ultrastructural features of nerve fascicles and basal lamina abnormalitiesin Hirschsprung's disease

Although the pathogenesis of Hirschsprung's disease (HD) is not completely resolved, both the absence of nerve cells and the hypertrophy of nerve fasc icles within the aganglionic colonic segment have been attributed to an abn ormal intestinal microenvironment. Studies on animal models for HD revealed an altered ultrastructure of ingrowing nerve fascicles and abnormalities o f basal laminae (BL). Therefore, the purpose of this study was to examine t he ultrastructure of hypertrophied nerve fascicles in human HD with special reference to structural abnormalities of BL. Colonic specimens were obtain ed from patients with HD (n=10) and controls (n=5) and processed for electr on-microscopical examination. Hypertrophied nerve fascicles were characteri zed by a prominent perineural sheath surrounded by large amounts of collage n bundles, a collagen-filled endoneurium, vasa nervorum and abundant glial cells of extraenteric ultrastructure, which were arranged in mono- or oligo -axonal units and frequently displayed different stages of myelination. As these ultrastructural characteristics resembled typical features of extrins ic nerves and were similar to those observed in subserosal nerves, the prom inent intramural nerve fascicles were considered to be of extraenteric orig in. Most likely their overabundance contributes to the functional obstructi on of the terminal colon. Morphological abnormalities of BL encountered in the aganglionic colonic segment consisted of an extensive multilamination o f BL surrounding glial processes and an irregular thickening of BL surround ing perineurocytes and smooth muscle cells of the muscularis mucosae. Simil ar alterations in BL have also been described in inherited peripheral and d iabetic autonomic neuropathies and attributed to reactivated Schwann cells. Thus, the overproduction of BL material within the hypertrophied nerve fas cicles in HD may reflect an increased activity of proliferating glial cells . Since the smooth muscle cells of the muscularis mucosae showed abnormalit ies of BL similar to those observed In murine models for HD, it is suggesti ve that also in human HD the aganglionic colon is affected by a disturbed i ntestinal microenvironment impairing the neuronal colonisation and promotin g the ingrowth of extrinsic nerves. The ultrastructurally observed alterati ons in BL of both neuronal and nonneuronal cells, as well as the increased amount of perineural and endoneural collagen provide further evidence that extracellular matrix components are abnormally distributed and overproduced within the bowel wall of patients affected by HD.