Updated results on intestinal neuronal dysplasia (IND B).

BACKGROUND: Intestinal neuronal dysplasia (IND B) is still a subject of controversy. The aim of this paper is to review the present state of knowledge on IND B. A summary is given of the technical and diagnostic criteria which have to be considered in order to arrive at a reliable diagnosis. In addition, the available therapeutic interventions are discussed.

METHODS: Between 1992 and 2001, 3984 colonic mucosal biopsies from 1328 children were investigated. Nerve cell staining was performed on native tissue sections: 15 microm thick cryostat sections, which, after spreading and drying on a microscopic slide, have a final thickness of 4-5 microm, with dehydrogenase reactions (lactic dehydrogenase, nitroxide synthase, succinic dehydrogenase). The biopsies were taken 8-10 cm above the dentate line (proximal to the ampulla recti, because of the caudo-cranial increase of giant ganglia proximal to the 4 cm biopsy) with a sufficient amount of submucosa. The criteria for IND is 15-20 % submucosal giant ganglia with more than eight nerve cells in 30 sections of a single biopsy (i.e. four to seven giant ganglia).

RESULTS: The diagnosis of IND B is quantitative. A diagnosis of IND B was made over the past 10 years in 51 Hirschsprung resections (about 5 per year; 6 % of all Hirschsprung cases), and in 92 children with chronic constipation (about 9 children per year; 2.3 % incidence). Up to their fourth year of life, most children with isolated IND can be treated conservatively. This is due to the delayed maturation of the enteric nervous system which is characteristic of IND B. Only children who showed an additional hypoplastic hypoganglionosis were treated surgically. Children with Hirschsprung's disease (HD) and IND B proximal to the aganglionosis often showed, in those cases with a disseminated IND, postoperative disturbances in intestinal motility.

CONCLUSION: The diagnosis of IND B requires that biopsies are taken proximal to the ampulla recti (about 8-10 cm above the dentate line) with a sufficient amount of submucosa. The biopsies must be cut rectangular to the surface of the mucosa. A diagnosis of IND B can be made only if, in the submucosa of 30 serial sections, 15-20 % of all ganglia are giant ganglia with more than eight nerve cells. Ganglioneuromatosis (MEN2B) must be clearly differentiated from IND. The clinical course of IND B depends on the extent of disturbed bowel innervation, the severity of motility failure, and the coexistence of MH. The conservative management of isolated IND is possible in most children. In individual cases, however, a transient enterostomy or a segmental resection is unavoidable.