Intestinal Neuronal Dysplasia Type B: An Updated Review of a Problematic Diagnosis

Abstract

Context.-Intestinal neuronal dysplasia type B (IND B) is a controversial histopathologic phenotype that has been associated with intestinal dysmotility, either as an isolated condition or in conjunction with established pathologic disorders (eg, Hirschsprung disease). Many factors contribute to the debate over the existence and/or clinical significance of IND B, including a large body of published data based on inconsistent diagnostic criteria and methods, which have fostered many unwarranted conclusions that lack sufficient scientific basis.Objective.-To critically analyze existing published data regarding IND B to provide supporting evidence-based diagnostic practice and to stimulate necessary and scientifically sound research.Data Sources.-This update focuses on published literature related to the pathology of IND B because without a reliable pathologic diagnosis, studies of epidemiology, pathogenesis, natural history, management, and outcome are all suspect. Problems with existing data are identified explicitly with suggestions as to how future investigations should be designed and evaluated to better understand this entity.Conclusions.-Inconsistencies in diagnostic criteria and methods used to define IND B justifiably encumber the universal acceptance of IND B as a neuropathologic etiology for intestinal dysmotility. IND B will remain a controversial diagnosis until rigorous, well-controlled scientific studies are conducted to establish reproducible and reliable diagnostic criteria that reliably translate from one laboratory to another.

Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia

“…Failures in development of ENS and consequent impairments will cause severe intestinal motor disorders, such as the complicated disorder NID. Many investigators have raised doubts about the existence of NID as a distinct histopathologic entity and suggested that the pathologic changes seen in IND may be a secondary phenomenon induced by intestinal obstruction and inflammatory disease [1,21]. The Tlx2 -/mice is a strong evidence that NID is a real entity.…”

“…Due to the similar clinical symptoms between NID and HSCR, definitive diagnosis still depends on histopathological analysis of rectal biopsies nowadays [1]. Rectal biopsy is a skillful and delicate method which only gives excellent results if it is carried out by a very competent surgeon [29].…”

“…Neuronal intestinal dysplasia (NID) is a clinical condition that resembles Hirschsprung's disease (HSCR) and is clinically characterized by seriously impaired colonic motility, such as severe constipation or intestinal obstruction [1,2]. Different from HSCR in histologically observation, absence of ganglion cells in the myenteric plexus, patients with NID show hyperplasia of the submucous and myenteric plexus with increase in AChE-positive nerve fibers [3].…”

“…Although pathological innervation patterns have been described in the colon of patients with NID, it remains controversial as to whether there is a causal relationship between histological findings and its seriously impaired colonic motility. Further-more, due to striking similarities among clinical features with HSCR, a definitive diagnosis of NID can be made only on histological analysis of rectal biopsies [1,4]. Therefore, a further research of the pathogenesis of NID and a more convenient and less painful diagnostic method are still needed.…”

Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B

“…IND-B is a rare disease that remains surrounded by several controversies ranging from its definition as a real disease to the different criteria for its diagnosis and treatment options 2,7,30 . Faced with all these uncertainties, physicians are routinely challenged about what to do with the results of rectal biopsies that reveal submucosal nerve plexus hyperplasia, leading to the diagnosis of IND-B in patients with severe constipation or intestinal obstruction 7 .…”