Shoba Krishnamurthy

Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus.

We analyzed the clinical, radiographic, esophageal manometric, and pathologic features of 26 women with severe, idiopathic constipation. Twenty-four patients were between 19 and 39 yr of age. Stool frequency was once every 5-28 days. On barium enema examination, 9 of 24 patients had colons of increased length and 4 of these 9 patients had colons of increased width (greater than 10 cm). Radionuclide solid-meal gastric-emptying studies were normal in 23 patients tested. Esophageal manometry demonstrated high-amplitude waves in 10 of 22 patients and long-duration waves in 3 of these 10 patients. Rectal biopsy specimens showed normal submucosal neurons in all patients and melanosis coli in 6. Twelve patients underwent subtotal colectomies for constipation. Conventional light microscopy using hematoxylin and eosin serial sections showed (a) melanosis coli in 4 patients; (b) normal smooth muscle in 11; (c) thinning of the circular muscle in 1; and (d) no apparent abnormalities of the myenteric plexus in any. In contrast, silver stains of the myenteric plexus showed (a) quantitatively reduced numbers of argyrophilic neurons in 10 patients; (b) morphologically abnormal argyrophilic neurons in 11; (c) decreased numbers of axons in 11; and (d) increased numbers of variably sized nuclei within ganglia in all 12. A coded analysis of the silver stains of colons from 8 patients with constipation and 19 control cases demonstrated that the pathologic abnormalities of severe idiopathic constipation could be differentiated from controls. Thus, severe idiopathic constipation is associated with a pathologically identifiable abnormality of the myenteric plexus. This abnormality appears different from anything previously described in intestinal pseudoobstruction.

Pathology of neuromuscular disorders of the small intestine and colon

A variety of pathological abnormalities of the smooth muscle and myenteric plexus result in clinical syndromes of disordered small intestinal and colonic motility. These pathological abnormalities have been noted by conventional light microscopy and by utilization of Smiths technique for visualizing the myenteric plexus with silver. We have classified the neuromuscular disorders into two major categories, i.e., those affecting the myenteric plexus and those affecting the smooth muscle. The classification is further developed based on the variety of clinicopathological features of the various disorders. Although we can now identify the underlying pathology of these motor disorders and thus understand these illnesses better than we did a decade ago, we have much more to learn. With the great strides being made to understand the normal structure, function, and development of the myenteric plexus and smooth muscle, there is hope that we will be able to learn much more about the etiology and pathogenesis of these neuromuscular disorders in the decade to come.

Subtotal colectomy for severe idiopathic constipation

We obtained follow-up information on 13 patients who underwent subtotal colectomy for severe idiopathic constipation 19–45 months previously. Stool frequency increased from one bowel movement per 11.5 days before colectomy to 5.3 bowel movements per day after colectomy. Nine patients have required readmissions for abdominal pain and four have required further surgery for symptoms of small bowel obstruction. Ten patients consider that their quality of life is improved, although five have variable amounts of fecal incontinence. Preoperative studies did not predict the three patients who failed to improve. Subtotal colectomy palliates constipation in most patients with severe idiopathic constipation but patients should be cautioned that not all improve and some are left with significant abdominal pain, obstructive symptoms, diarrhea, and fecal incontinence.

Megacolon and Neurofibromatosis: A Neuronal Intestinal Dysplasia: Case Report and Review of the Literature

This study presents the case of a patient with neurofibromatosis and megacolon. A diffuse, but patchy abnormality of neural tissue was present throughout the colon, especially in the myenteric plexus, but also in the submucosal plexus, smooth muscles, and lamina propria. This consisted of (a) a marked decrease in the number of argyrophilic neurons within the myenteric plexus, enlargement and deformity of those neurons present, and a marked increase of nerve fibers and nerve tract size in the myenteric plexus; (b) a proliferation of neurons and nerve fibers within the smooth muscle and submucosa; and (c) a proliferation of nerve fibers within focal areas of the lamina propria. The relationship of this case to previously reported cases of neuronal intestinal dysplasia and plexiform neurofibromatosis is discussed. Surgical treatment may be necessary and the surgical options are reviewed.

Chronic intestinal pseudo-obstruction in infants and children caused by diverse abnormalities of the myenteric plexus

BACKGROUND Chronic intestinal pseudo-obstruction is a motility disorder that leads to severe disability in infants and children. Our purpose was to study the myenteric plexus in infants and children with pseudo-obstruction METHODS Using cross sections stained with H&E and frozen tangential sections of the myenteric plexus processed using Smiths silver technique, the myenteric plexus of the stomach, small intestine, and colon from 26 affected infants and children was analyzed quantitatively. RESULTS Under H&E staining, there were decreased neuron scores of 34.1 +/- 7.4 and 25.3 +/- 7.1 in the jejunum and ileum (normal, 57.5 +/- 6.2 and 55.0 +/- 4; P = 0.005 for both). Using Smiths technique, the specimens had decreased argyrophilic neuron counts of 3.1 +/- 1.4, 3.6 +/- 1.1, 3.4 +/- 1.0, and 2.8 +/- 0.6 in the duodenum, jejunum, ileum, and colon, respectively (normal, 14.0 +/- 1, 14.8 +/- 1, 14.7 +/- 0.5, and 13.6 +/- 1.1; P < 0.0003). The abnormalities included (1) absence of myenteric plexus in 3 patients; (2) small numbers of neuronal structures present on H&E stains but the absence of the plexus on silver stains in 2; and (3) myenteric plexus present but decreased argyrophilic neurons and axons on silver stains in 18. The abnormalities would have been missed in 10 patients if H&E had been used alone, whereas Smiths technique identified the deficiency of argyrophilic neurons in all patients tested. CONCLUSIONS Pseudo-obstruction in infants and children may be caused by diverse abnormalities of the myenteric plexus.

Megacolon in Myotonic Dystrophy Caused by a Degenerative Neuropathy of the Myenteric Plexus

A 32-yr-old man with myotonic dystrophy had a left hemicolectomy performed because of a megacolon. The colonic mucosa, smooth muscle, and connective tissue appeared normal by hematoxylin and eosin and trichrome stains and transmission electron microscopy. In contrast, the myenteric plexus had markedly fewer neurons than normal on the hematoxylin and eosin stains. Silver staining of the plexus revealed degeneration and decreased numbers of argyrophilic neurons, which were smaller and had fewer processes and a more uneven staining quality than controls. Many axons were fragmented, and increased numbers of glial cell nuclei were present in the plexus. Degenerative changes in the neurons were present in a patchy distribution on transmission electron microscopy. Immunohistochemistry revealed a decrease of the substance P- and enkephalin-immunoreactive fibers in the muscularis externa. This suggests that colonic motor dysfunction associated with myotonic dystrophy may be caused by a visceral neuropathy that involves the substance P- and enkephalin-immunoreactive fibers of the smooth muscle.

Intestinal pseudoobstruction caused by a new form of visceral neuropathy: Palliation by radical small bowel resection

We report a case of chronic intestinal pseudoobstruction caused by a newly recognized type of degenerative neuropathy of the myenteric plexus. Failure to improve despite aggressive medical management led to radical resection of the clinically involved small intestine. At follow-up 10 mo later, the patient is doing well without the need for parenteral nutrition. Radical resection of the small intestine may be necessary for palliation in rare patients with intractable pseudoobstruction.

An Inflammatory Axonopathy of the Myenteric Plexus Producing a Rapidly Progressive Intestinal Pseudoobstruction

A previously well 39-yr-old man presented with a 4-wk history of abdominal pain, nausea, vomiting, and weight loss. An upper gastrointestinal examination showed retained food in the stomach and duodenal dilatation. A radioisotope meal showed little gastric emptying; esophageal manometry was normal. Because of persistent symptoms, a duodenojejunostomy was done. However, the patient remained symptomatic and after an episode of profuse vomiting, aspirated and died 10 wk after initial presentation. At autopsy, no tumor was found. Hematoxylin and eosin stains throughout the gastrointestinal tract showed many lymphocytes and plasma cells within the myenteric plexus. Silver stains showed the argyrophilic and argyrophobic neurons to be normal, but axons showed beading, fragmentation, and dropout in all areas. We therefore concluded the following: intestinal pseudoobstruction can be caused by an inflammatory neuropathy of the myenteric plexus, not associated with a distant carcinoma, and this process produced an axonopathy while sparing neuron bodies.

Constipation and colectomy

underwent subtotal colectomy were incapacitated by their colonic disease and achieved symptomatic relief. Two patients, one with severe monthly symptoms lasting two to three days and an asymptomatic patient were not incapacitated by their disease and were not operated on. Like Schuffler and coworkers (4, 5), we make a distinction between patients with severe idiopathic constipation and patients with idiopathic pseudoobstruction. Patients with severe idiopathic constipation have no gaseous abdominal distension and usually have a flat abdomen and little stool in the colon relative to the time interval from the last bowel movement. Patients with colonic pseudoobstruction have gaseous distension of the colon, most of them having a clinical picture mimicking bowel obstruction, and may or may not have constipation. Thus severe idiopathic constipation is a related, but somewhat dissimilar, syndrome (4). It appears that subtotal colectomy produced symptomatic relief in all patients with isolated colonic pseudoobstruction (1), but only in some patients with severe idiopathic constipation (6, 7). Our resuits of colectomy and ileosigmoid anastomosis in eight females with severe idiopathic constipation (unpublished data) are in agreement with the outcome reported in similar patient groups by Leon et al (6) and Preston et al (7). After subtotal colectomy, five of our eight patients with severe idiopathic constipation are doing well, have no abdominal pain, and have spontaneous bowel movements (one per day to one per week). One patient has 10 diarrheal stools per day and continuous abdominal pain which is less severe than prior to surgery. Two patients have stopped having spontaneous bowel movements 0.3 and 0.5 years after colectomy. We believe that subtotal colectomy should be an option for patients who lead miserable lives because of disabling colonic disease that is unrelieved by medical treatment. Only by long-term follow-up of our patients will we know if the disease will develop in other parts of the gastrointestinal tract, and if symptomatic relief was only temporary. VERA LOENING-BAUCKE, MD SINN ANURAS, MD University of Iowa Hospitals & Clinics Iowa City, Iowa 52242 Texas Tech University Health Sciences Center Lubbock, Texas 79430 REFERENCES