The term gastrointestinal neuromuscular disease describes a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular, including interstitial cell of Cajal, dysfunction. Such disorders commonly have impaired motor activity, i.e. slowed or obstructed transit with radiological evidence of transient or persistent visceral dilatation. Whilst sensorimotor abnormalities have been demonstrated by a variety of methods in these conditions, standards for histopathological reporting remain relatively neglected. Significant differences in methodologies and expertise continue to confound the reliable delineation of normality and specificity of particular pathological changes for disease. Such issues require urgent clarification to standardize acquisition and handling of tissue specimens, interpretation of findings and make informed decisions on risk-benefit of full-thickness tissue biopsy of bowel or other diagnostic procedures. Such information will also allow increased certainty of diagnosis, facilitating factual discussion between patients and caregivers, as well as giving prognostic and therapeutic information. The following report, produced by an international working group, using established consensus methodology, presents proposed guidelines on histological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology. The report addresses the main areas of histopathological practice as confronted by the pathologist, including suction rectal biopsy and full-thickness tissue obtained with diagnostic or therapeutic intent. For each, indications, safe acquisition of tissue, histological techniques, reporting and referral recommendations are presented.

This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available.

Aging of the brain involves not only appreciable shrinkage of the cortex and other gray matter structures but above all loss of white matter. This could be due to a decline in the number of myelinated fibers or to a loss of water. To assess the role played by each of these factors we studied brains from 33 neurologically intact subjects at autopsy representing three different age groups: 15-50, 51-70, and 71-93 years. The precentral gyrus, gyrus rectus, and corpus callosum were selected for investigation, with staining for alkaline phosphatase on native cryostat sections to visualize the capillary network, and staining for myelin on semithin sections for nerve fiber visualization. Atrophy was objectified by measuring the number of capillaries, the intercapillary distance, and capillary length, since the capillary network remains constant throughout normal life. A mean difference of 16-20% was found, representing white matter atrophy, between the oldest and youngest age-groups. The cortex of the corresponding gyri, on the other hand, showed a difference of less than 6%. Morphometric investigation of sections stained for myelin showed that the brains with a mean age of 78.7 +/- 6.6 years had 10-15% fewer myelinated fibers. This was only partly offset by an increase in the volume of extracellular space. Our findings show that the age-related decline in brain volume is much more a question of white matter atrophy than of brain cortex atrophy. White matter atrophy could be an indirect indicator of nerve cell loss, since the volume of a nerve cell is much smaller than its myelinated fiber.

Intestinal Dysganglionoses (IDs) represent a heterogeneous group of Enteric Nervous System anomalies including Hirschsprung's disease (HD), Intestinal Neuronal Dysplasia (IND), Internal Anal Sphincter Neurogenic Achalasia (IASNA) and Hypoganglionosis. At present HD is the only recognised clinico-pathological entity, whereas the others are not yet worldwide accepted and diagnosed. This report describes the areas of agreement and disagreement regarding definition, diagnosis, and management of IDs as discussed at the workshop of the fourth International Meeting on "Hirschsprung's disease and related neurochristopathies." The gold standards in the preoperative diagnosis of IDs are described, enlighting the importance of rectal suction biopsy in the diagnostic workup. The most important diagnostic features of HD are the combination of hypertrophic nerve trunks and aganglionosis in adequate specimens. Acetylcholinesterase staining is the best diagnostic technique to demonstrate hypertrophic nerve trunks in lamina propia mucosae, but many pathologist from different centers still use H&E staining effectively. Moreover, the importance of an adequate intraoperative pathological evaluation of the extent of IDs to avoid postoperative complications is stressed. Although it is not clear whether IND is a separate entity or some sort of secondary acquired condition, it is concluded that both IND and IASNA do exist. Other interesting conclusions are provided as well as detailed results of the discussion. Further investigation is needed to resolve the many controversies concerning IDs. The fourth International Conference in Sestri Levante stimulated discussion regarding these entities and led to the International guidelines to serve the best interest of our patients.

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.