Megacolon homozygous disease
Macrocolic homologous disease (ADHD) is a complex disorder of intestinal motility dysfunction caused by abnormalities in the innervation of the intestinal nerves. It is similar to macrosomia in clinical signs and symptoms but has completely different pathological changes and does not show ganglion cell loss.
I. Ganglion cytopenia
Ganglion cytopenia (HYPG) is less common as an isolated disease, often more or less present in the proximal part of the diseased intestinal segment in children without ganglion cell disease and anorectal disease, accounting for 5% of NIM, and the diagnosis should be based on whole-layer biopsy. The pathology is characterized by sparse and small ganglion cells in the intermuscular plexus and sometimes in the submucosal plexus as well.
Ganglion cells per centimeter of longitudinal intestinal wall are at least 30% less than normal, and the plexus area is reduced to 20% of normal. AChE activity is low or absent in the lamina propria of the mucosa, and there is hyperplasia of the cricoid muscle and submucosa. Simple gangliocytopenia presents with severe constipation or even pseudo-obstruction from neonatal onwards and a constant dilatation of the colon very similar to HD symptoms. Treatment requires resection of the diseased intestinal segment, and the extent of the lesion can be determined intraoperatively using rapid acetylcholinesterase histochemical techniques.
Intestinal neuronal dysplasia
Meier-Ruge (1983) and others pointed out that the incidence of enteric neurodevelopmental dysplasia (IND) is similar to that of HD, while Garrett 1981 and Risdon 1989 suggested that it is 5% less than HD, and Fadda 1987, Schärli 1992, and Kobayashi 1995 reported that 25%-35% of HD is combined with IND. The diagnostic rate varies greatly depending on the diagnostic criteria used, the staining method and the specimen taken, e.g., the incidence of isolated IND is reported to be 0.3%-40%.
The diagnostic criteria for IND have changed over the years. In the 1970s, increased ganglion cells and increased AChE activity in the lamina propria of the mucosa were the criteria, in the 1980s increased AChE-positive fibers in the lamina propria of the mucosa were important indicators, and in the early 1990s Borchard proposed increased submucosal plexus, increased acetylcholinesterase positive fibers around the submucosal vessels, and ectopic ganglion cells and increased AChE activity in the lamina propria of the mucosa as criteria. criteria.
In 1994, Meier-Ruge et al. reported that giant ganglia are an important diagnostic marker, and that giant ganglia can be seen not only in infants but also in adults, because the increased AChE activity in the submucosal muscle layer and submucosal plexus disappears with age in early infancy and is rarely seen after 2 years of age. Fadda classified IND into two types, A and B.
1, Type A IND.
Type A is extremely rare, accounting for 2% to 5% of NIM, pathological changes are reduced, lack of and dysplasia of sympathetic nerve fibers in the intermuscular plexus and mucosa. There is a mild increase in AChE activity in the lamina propria, submucosa and circumflex muscles and an increase in the myoneural plexus. Clinically, acute intestinal obstruction, diarrhea, and bloody stools usually present within 2 years of age. Surgical removal of the diseased intestinal segment is required.
2. Type B IND.
Most of the type B IND is isolated type, a small number of coexisting with HD, about 20-40% of patients with symptoms of megacolon for type B IND, Puri (1997) that isolated type accounted for 95%, Meier-Rugel 1994 reported in 773 cases of constipation patients intestinal biopsy, 209 cases (27%) type B IND, of which 64 (30.6%) cases with HD coexisting with HD. The pathology was characterized by hyperplasia of the submucosa and intermuscular plexus, thick nerve fibers with giant ganglia, which were about 3 times larger than normal and had 3 times more nerve cells per ganglion, containing at least 7 ganglion cells, each of which was smaller than normal.
As the submucosal plexus matures with age, the activity of AChE decreases and gradually disappears from about the second year of life, so that in adults the diagnosis of type B IND is indicated by an increase in the number of giant ganglia. Other indicators are the presence of ectopic ganglion cells in the lamina propria of the mucosa sometimes in the muscularis, especially in the circular or longitudinal muscle layers, and defects at the neuromuscular junction, which may be caused by the lack of synaptic cord (SY) neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP-43), and synaptic immunoreactivity in smooth muscle.
Type B IND has similar symptoms to HD in early infancy, manifesting as pseudo-intestinal obstruction in the distal colon, and can manifest varying degrees of constipation due to different degrees of submucosal plexus lesions, which can have absorption disorders and persist until 6 years of age or older; in some cases, the degree of constipation is more or less reduced after 2 to 3 years of age. Most cases can be treated conservatively, and a few cases with persistent constipation in adulthood can be treated surgically with posterior sagittal internal sphincterotomy and resection of the diseased bowel segment.
Third, ganglion cell immaturity
Ganglion immaturity (IMG) can be an independent disease that manifests as functional intestinal obstruction. Since immature ganglion cells can be moderately mature within 24 months after birth and can reach normal morphology and function after 3-4 years, the diagnosis cannot be made clearly within the first year after birth. Pathological changes are small both ganglion and ganglion cells, low or lack of LDH staining reaction in immature ganglion cells, increased nuclear structures between cytoplasm and nucleus, and even cell complexes. Severe hypoplasia of the submucosal plexus can lead to severe intestinal motor dysfunction. Conservative treatment is feasible for this type.
IV. Internal sphincter spasm
Internal sphincter spasm is clinically similar to HD, but the pathology has ganglion cells, a negative reflex on rectal anal canal manometry, and pathological changes such as decreased NCAM in smooth muscle, loss of NADPH dehydrogenase, and increased AChE activity.NADPH dehydrogenase is a regulator of smooth muscle relaxation in the gastrointestinal tract, and NADPH dehydrogenase deficiency leads to IAS spasm. The disease can be successfully treated by internal anal sphincterotomy.
V. Silver-loving plexus deficiency
In the normal enteric plexus there are two types of neurons that can be distinguished by silver staining, one is silverophilic and the other is non-silverophilic. Silverophilic accounts for 5%-20% of the total neurons, and silverophilic cells in the plexus along the lateral sympathetic and parasympathetic fibers constitute a nerve net. This nerve network controls intestinal peristalsis and ensures that the intestinal contents move forward at the correct speed.
The silver cells appear to secrete neurotransmitters that determine the contraction or relaxation of muscle fibers, all of which are under the control of the silver cells. In patients with gammophile deficiency, gammophile cells may be completely absent while AChE histochemistry and neural markers are normal. Treatment can be conservative or by internal anal sphincterotomy.
Combined type
Macrocolon and its homologous disease can exist in various forms of combination, such as HD and IND, and the largest proportion of HD combined with B-type IND. This is followed by the combination type of IND with ganglion cytopenia, with ganglion cell dysplasia or ectopic. These types require a different surgical or conservative treatment than HD.
There are also cases in which it is difficult to determine which type belongs, for example Meier-Ruge (1992) reported that approximately 30% of biopsied patients fall into this category, with morphologic changes including mild or borderline IND, mild submucosal plexus developmental abnormalities, and ectopic ganglion cells. When such changes are only mild lesions it remains unclear how they affect bowel function or whether they are a secondary alteration.
In conclusion, it has been debated whether megacolon homozygosity is a definitive clinical disease, and many scholars believe that it is a secondary change (Rintala 1989, Stoss 1991, Bussmann 1990), but in recent years the findings have tended to be positive. Although ganglion cells are present and clinically similar to HD, it can be diagnosed by various histological methods, has definite pathological changes, has not only submucosal and myoneural abnormalities, but also defects of the muscular and neuromuscular junction and anal sphincter, and can be cured by surgical and non-surgical methods.