Hypoperistalsis Syndrome Research Articles

Megacystis‐Microcolon‐Intestinal Hypoperistalsis Syndrome

The purpose of this report is to describe the in utero sonographic appearance of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) and examine the role of vesicocentesis. Two cases of the sonographic appearance of MMIHS were reviewed. We performed vesicocentesis in 2 fetuses with MMIHS and performed vesicoamniotic shunting in 1 of them. The sonographic findings after these procedures were compared with those before puncture. In both cases, ultrasound examination showed a massively enlarged fetal bladder and bilateral hydroureteronephrosis with a normal amount of amniotic fluid. Fetal urinary sodium and chloride concentrations were within normal limits in both cases; this suggested normal fetal renal function. Generally, it is difficult to detect the dilated fetal bowel in MMIHS, probably because of the disturbance caused by a large bladder. In our cases, however, the ultrasound examination clearly showed fetal bowel dilatation after these procedures; this made the antenatal diagnosis of MMIHS more definite. The sonographic features after vesicocentesis may be helpful in confirming the antenatal diagnosis of MMIHS.

Structural basis of voiding dysfunction in megacystis microcolon intestinal hypoperistalsis syndrome

Purpose Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare, congenital and usually fatal condition of unknown etiology. It is characterized by abdominal distension caused by a distended, non-obstructed urinary bladder and intestinal hypoperistalsis with functional intestinal obstruction. Previous studies reported vacuolar degenerative changes in the smooth muscle cells of bowel and bladder suggesting that MMIHS may be due to a visceral myopathy. The aim of this study was to examine the expression of contractile, cytoskeletal and extracellular matrix proteins in the detrusor muscle of MMIHS patients. Material and methods Bladder specimens were obtained from six MMIHS patients. Normal bladder specimens were obtained during partial cystectomy and served as controls. Single fluorescence immunohistochemistry for α-smooth muscle actin (SMA), desmin, dystrophin, vinculin and collagen types I and III was carried out. Specific connective tissue stains (trichrome Masson, van Gieson) and electron microscopical investigations were also performed. Results Trichrome Masson and van Gieson staining demonstrated markedly increased dense connective tissue between the layers of the detrusor muscle in MMIHS compared to controls. Collagen type I immunoreactivity was markedly increased and SMA, desmin and dystrophin immunoreactivity was markedly reduced in the bladder muscle of MMIHS compared to controls. Electron microscopy revealed vacuolar degenerative changes in smooth muscle cells and an abundance of connective tissue between these cells. Conclusion These data suggest that the detrusor muscle in MMIHS is strikingly abnormal and is the likely cause of voiding dysfunction.

Complexité de l’interprétation anatomopathologique dans le syndrome mégavessie-microcôlon-hypopéristaltisme intestinal

Megacystis-microcolon-intestinal hypoperistalsis syndrome is very rare, and is the most severe of the chronic intestinal pseudoobstructions. Diagnosis is usually made in the neonatal period, is clinical and radiological, and is confirmed by manometric studies. Microscopic abnormalities are variable, inconstant and nonspecific. They involve the smooth muscle more often than the intrinsic innervation of the gut and the bladder. A girl, currently seven years old, presented with megacystis observed on prenatal ultrasound at 21 weeks of gestation. At first, amniotic fluid volume was appropriate for gestational age, and then hydramnios appeared at 30 weeks of gestation. Microcolon was discovered at birth, with microileum, dilatation of the duodenum and proximal jejunum, intestinal malposition, and severe hypoperistalsis of the entire gastrointestinal tract, which indicated enterostomy and total parenteral nutrition from birth. At pathological examination, rectal biopsy and enteric nervous plexuses were normal. There was hypoplasia of the external longitudinal layer of the muscularis propria in the colon and ileum. Cajal cells could not be demonstrated immunohistochemically in the colon. This case highlights the complexity and difficulties of pathological interpretation in this syndrome, and the necessity of a large study of controls at different ages and different levels of the digestive tract and the bladder.

Intestinal and multivisceral transplantation in children with severe gastrointestinal dysmotility

Background/Purpose Severe gastrointestinal dysmotility (GID) impairs patients' quality of life and is almost uniformly fatal after complications of parenteral nutrition. Intestinal and multivisceral transplants have been used as alternative treatment of these disorders. We studied patients with GID treated with transplantation in our center, and reviewed their outcome to determine the therapeutic efficacy of multivisceral transplants. Methods The transplant database was searched for patients with GID from 1994 to 2001. We excluded patients with Hirschsprung disease, scleroderma, and diabetic enteropathy. We reviewed explanted organs, histochemistry, and immunohistochemistry and classified cases by etiology. Results We selected 12 children with GID from 124 patients transplanted. Nine presented before 1 year and 3 started with symptoms between 2 and 8 years. By combined clinical and histopathological features, 6 were classified as megacystis microcolon intestinal hypoperistalsis syndrome, 4 as chronic idiopathic intestinal pseudoobstruction, and 2 as intestinal neuronal dysplasias. Six patients died during the follow-up from 21 to 546 days after transplant. The Kaplan-Meier actuarial survival rates were 66.7% at 1 year and 50% at 3 years. Conclusions Multivisceral transplantation is a valuable therapeutic alternative for children with severe GID who cannot be adequately managed with parenteral nutrition.

Prenatal diagnosis of megacystis‐microcolon‐intestinal hypoperistalsis syndrome: contribution of amniotic fluid digestive enzyme assay and fetal urinalysis

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a usually lethal disease during the first year of life. There is no specific ultrasound prenatal diagnosis and no identified genetic locus. The value of amniotic fluid digestive enzyme assay and fetal urine biochemistry in the prediction of MMIHS was analysed. Retrospective study of 14 MMIHS cases. Amniotic fluid digestive enzymes and fetal urine biochemistry were compared in MMIHS and megabladder (63 and 264 cases respectively). Abnormal amniotic fluid digestive enzyme profile (vomiting of bile or digestive secretion leakage) was observed in 8/10 MMIHS cases. These profiles were observed in 7/63 controls; 80% sensitivity (95%CI = 55%-100%); 89% specificity (95%CI = 81%-96%). Fetal urinalysis was normal in 12/12 MMIHS cases except high calcium (>0.6 mmol/l). This profile was observed in 33/264 megabladder control cases; 100% sensitivity; 98.7% specificity (95%CI = 83.5%-91.5%). For the first time, we propose a prenatal diagnosis of MMIHS based on amniotic fluid digestive enzyme assay and on fetal urinalysis.

Megacystis microcolon intestinal hypoperistalsis syndrome

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and the most severe form of functional intestinal obstruction in the newborn. The major features of this congenital and usually lethal anomaly are abdominal distension, bile-stained vomiting, and absent or decreased bowel peristalsis. Abdominal distension is a consequence of the distended, unobstructed urinary bladder with or without upper urinary tract dilation. Most patients with MMIHS are not able to void spontaneously. This article reviews the pathogenesis of MMIHS as well as the clinical, radiological, surgical and histological findings in all reported cases of this syndrome.

Interstitial cells of cajal in the human normal urinary bladder and in the bladder of patients with megacystis‐microcolon intestinal hypoperistalsis syndrome

OBJECTIVE To investigate the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in normal bladder and bladders from patients with megacystis-microcolon-intestinal peristalsis syndrome (MMIHS, a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn), the most characteristic feature of which is abdominal distension caused by a distended unobstructed urinary bladder. PATIENTS AND METHODS Full-thickness bladder specimens were obtained from four infants with MMIHS and four controls, and processed as paraffin-wax and frozen sections. Sections were assessed using single immunohistochemistry with monoclonal and polyclonal anti-c-kit antibodies. Anti-α-smooth muscle actin (SMA) antibody was used to investigate the contractile apparatus in smooth muscle cells of the urinary bladder. Specimens were examined using light and confocal scanning microscopy. RESULTS There were many c-kit positive ICCs in the normal urinary bladder, appearing as small, long, bipolar cells with only two long and several short processes. In contrast, ICCs were absent in the MMIHS bladder. α-SMA immunoreactivity was lower in MMIHS urinary bladder than in control sections. CONCLUSION This study shows for the first time the presence of c-kit-positive ICCs in the normal human urinary bladder. The lack of ICCs in the MMIHS bladder may contribute to the voiding dysfunction in this disease.

Découverte anténatale à 12 semaines d’aménorrhée d’un syndrome « intestinal hypoperistalsis mégacystis-microcolon » (MMIHS)

Megacystis on antenatal scan in female fetuses is rare and has diagnostic implications. We report a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in a female infant. The antenatal scan revealed abnormalities, but the diagnosis was not established until after delivery. MMIH is a rare autosomal recessive condition which is usually lethal in the first year of life. Prenatal diagnosis is hampered by the lack of specific diagnostic ultrasound findings and the absence of an identified genetic locus.

Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disorder characterized by a dilated, non-obstructive urinary bladder and hypoperistalsis of the gastrointestinal tract, which is considered lethal. About 90 patients have been reported, predominantly female. We present the case of a female newborn with MMIHS in whom antenatal ultrasound was suggestive for the diagnosis, which was confirmed after delivery. Diagnostic features by antenatal ultrasound are described.

Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disorder characterized by a dilated, non-obstructive urinary bladder and hypoperistalsis of the gastrointestinal tract, which is considered lethal. About 90 patients have been reported, predominantly female. We present the case of a female newborn with MMIHS in whom antenatal ultrasound was suggestive for the diagnosis, which was confirmed after delivery. Diagnostic features by antenatal ultrasound are described.

Interstitial cells of Cajal in the human normal urinary bladder and in the bladder of patients with megacystis-microcolon intestinal hypoperistalsis syndrome.

To investigate the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in normal bladder and bladders from patients with megacystis-microcolon-intestinal peristalsis syndrome (MMIHS, a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn), the most characteristic feature of which is abdominal distension caused by a distended unobstructed urinary bladder. Full-thickness bladder specimens were obtained from four infants with MMIHS and four controls, and processed as paraffin-wax and frozen sections. Sections were assessed using single immunohistochemistry with monoclonal and polyclonal anti-c-kit antibodies. Anti-alpha-smooth muscle actin (SMA) antibody was used to investigate the contractile apparatus in smooth muscle cells of the urinary bladder. Specimens were examined using light and confocal scanning microscopy. There were many c-kit positive ICCs in the normal urinary bladder, appearing as small, long, bipolar cells with only two long and several short processes. In contrast, ICCs were absent in the MMIHS bladder. alpha-SMA immunoreactivity was lower in MMIHS urinary bladder than in control sections. This study shows for the first time the presence of c-kit-positive ICCs in the normal human urinary bladder. The lack of ICCs in the MMIHS bladder may contribute to the voiding dysfunction in this disease.

Síndrome de megavejiga-microcolonhipoperistaltismo intestinal. A propósito de un caso de supervivencia prolongada

Megacystis-microcolon-intestinal hypoperistalsis syndrome is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. It is an uncommon disorder with high morbidity and mortality, and long-term total parenteral nutrition may be required. We describe an 18-year-old girl with long-term survival, followed-up by our service since birth. With medical, surgical and nutritional management she currently presents a good oral tolerance and good quality of life, only requiring parenteral nutrition during periods of decompensation.

The fungal DNA examination is useful as a sensitive parameter for the initiation and the quit of antifungal therapy in immunocompromised pediatric patients after surgery.

The purpose of this study is whether the fungal deoxyribonucleic acid (DNA) examination is useful as a sensitive parameter for pediatric surgical patients with mycosis. The eleven episodes of five cases (4 cases; progressive liver disease after biliary atresia operation, 1 case; short bowel syndrome and long term total parenteral nutrition with megacystis microcolon intestinal hypoperistalsis syndrome) with mycosis were divided into two groups according to the difference of therapeutic protocols. The sensitivity of fungal DNA examination, serum Candida antigen level, plasma beta-D glucan level, and blood culture were evaluated at the onset of infection and at the quit of antifungal medication under the protocols respectively. The duration of medication and the medication free interval in two groups were compared. The 6 episodes (3 cases) were diagnosed and treated under the protocol not including fungal DNA examination, while the 5 episodes (2 cases) under the protocol including fungal DNA examination. The occurrence rate was not significant. The sensitivity of fungal DNA examination was complete, but others were not. Using the fungal DNA examination, the duration of medication became significantly short. We conclude that the fungal DNA examination could be a sensitive parameter not only to start but to quit antifungal medication in pediatric patients with mycosis.

Megacystis microcolon intestinal hypoperistalsis syndrome with bilateral duplicated systems

A 29-year-old multigravida woman presented for her second prenatal ultrasound evaluation at 30 weeks of gestation. The study showed a female fetus, bilateral duplicated systems with severe hydronephrosis in the upper pole moieties and a massively distended bladder. Initial interpretation suggested ectopic/obstructing bilateral ureteroceles. To evaluate these findings further, a prenatal magnetic resonance imaging scan was obtained, documenting the absence of ureteroceles. The presumptive diagnosis of megacystis microcolon intestinal hypoperistalsis syndrome was made. After birth, contrast enema confirmed the presence of microcolon. This appears to be the first reported case of megacystis microcolon intestinal hypoperistalsis syndrome with bilateral duplex systems evaluated with prenatal magnetic resonance imaging.

Enlarged fetal bladder: Differential diagnosis and outcomes.

The sonographic finding of an enlarged fetal bladder may simply be a transitory normal variant, but it may also be secondary to reflux or to obstructive, neurogenic, or myopathic causes. In this report, we describe the cases of 3 fetuses with an enlarged bladder, each of which had a different cause. The first fetus had posterior urethral valve obstruction, the second, a ruptured neurogenic bladder, and the third, megacystic-microcolon-intestinal hypoperistalsis syndrome. When sonographic examination reveals an enlarged fetal bladder, the ureter, kidneys, genitalia, and spine should be evaluated carefully. Although sonography is good at identifying urinary tract abnormalities, it often cannot provide the specific diagnosis or cause. We recommend frequent sonographic monitoring to evaluate such fetuses for persistence of or changes in bladder enlargement and for changes in the volume of amniotic fluid because these signs may be indicators of abnormalities of renal function and risk factors for a poor prognosis. Analysis of fetal electrolyte levels can also aid in determining the prognosis and whether the condition is amenable to therapeutic intervention.

Alterations in smooth muscle contractile and cytoskeleton proteins and interstitial cells of Cajal in megacystis microcolon intestinal hypoperistalsis syndrome

Background/Purpose: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is characterized by decreased or absent peristalsis. Gastrointestinal motility depends on the enteric nervous system, smooth muscle cells (SMCs), and the interstitial cells of Cajal (ICCs). Contractile and cytoskeleton proteinase are important structural and functional components of SMCs. The aim of study was to examine the expression of contractile and cytoskeleton proteins in SMCs and distribution of ICCs in MMIHS bowel. Methods: Full-thickness bowel specimens were obtained from 4 infants with MMIHS and 4 controls. Specimens were processed as whole-mount preparations and frozen and paraffin sections. Combined staining of NADPH-d histochemistry/c-kit immunohistochemistry, single and double immunohistochemistry using α-smooth muscle actin (α-SMA), calponin (CALP), caldesmon (CALD), desmin (DES), protein gene product 9.5 (PGP 9.5) and c-kit antibodies were performed and examined using light and confocal scanning microscopy. Results: α-SMA, CALP, CALD, and DES immunoreactivity were reduced markedly in MMIHS bowel compared with controls. Combined NADPH/c-kit staining showed dense network of ICCs around myenteric plexus in MMIHS bowel. In contrast, the intramuscular ICCs either were absent or reduced in MMIHS bowel. Conclusions: Marked reduction of contractile and cytoskeleton proteins in SMCs combined with reduced expression of intramuscular ICCs in the gut may be responsible for the motility dysfunction in MMIHS. J Pedriatr Surg 38:749-755. © 2003 Elsevier Inc. All rights reserved.

Severe megacystis and bilateral hydronephrosis in a female fetus

The differential diagnosis for antenatal bladder dilation and hydronephrosis is extensive, ranging from posterior urethral valves to neurogenic bladder. We present a case of a female fetus diagnosed antenatally with severe megacystis and bilateral hydroureteronephrosis. The patient was found to have megacystis-microcolon-intestinal hypoperistalsis syndrome, a rare, congenital, and generally fatal disorder in which there is functional obstruction of the bladder and intestine.

Megacystis‐microcolon‐intestinal hypoperistalsis syndrome and aganglionosis in trisomy 18

Megacystis‐microcolon‐intestinal hypoperistalsis syndrome and aganglionosis in trisomy 18

Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the α3 nicotinic acetylcholine receptor subunit

Background & Aims: The megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare disease of childhood that presents early with intestinal hypoperistalsis, hydronephrosis, and hydroureters.Transgenic mice that lack the α3 subunit containing nicotinic acetylcholine (nAChR) have a phenotype similar to that of MMIHS.Methods: We examined the expression of this subunit in control and MMIHS tissue derived from patients using in situ hybridization (ISH) and immunocytochemistry (ICC).Results: In controls, both techniques showed a wide distribution of α3 nAChRs present in ganglion cells, muscle, and epithelium.By contrast, most MMIHS tissue gave negative staining with ISH and variable results with ICC.Conclusions: These observations are consistent with a lack of α3 nAChRs contributing to the pathogenesis of MMIHS.GASTROENTEROLOGY 2001;121:350-357

New pathogenetic aspects of gut dysmotility in aplastic and hypoplastic desmosis of early childhood.

The peristaltic movement of the gut is a function of the alternating contraction and relaxation of circular and longitudinal muscles. This movement is induced by a tendon-like connective-tissue net (TCTN) in the circular and longitudinal muscles, which are both rooted in a connective-tissue plexus layer (CTPL). In children with a therapy-resistant aperistaltic or hypoperistaltic syndrome who had normally-developed enteric innervation, a lack of the TCTN in the muscularis propria was observed. Over the last 2 years, 241 children with chronic constipation were investigated histopathologically; 46 children surgically treated by partial resection of the gut or diagnostically investigated by whole-mount biopsy. Fifteen children had a hypoperistalsis syndrome and 3 had an aperistalsis syndrome. All specimens were native and cut in a cryostat. Enteric innervation was examined by acetylcholinesterase and dehydrogenase reactions. The TCTN in the muscularis propria was stained with picric acid/sirius red. In the children with an aperistalsis syndrome, a complete lack of the TCTN in circular and longitudinal muscles was observed. A CTPL was not developed. The children with a hypoperistalsis syndrome had no CTPL, but had a partly-developed TCTN in the circular and longitudinal muscles, which gradually faded in the direction of the plexus layer. Independent of a well-developed enteric nervous system, a lack of the TCTN in longitudinal and circular muscles and a missing CTPL (aplastic desmosis) abolishes the coordinated peristaltic movement of the gut. An isolated lack of the CTPL in the myenteric plexus (hypoplastic desmosis) results in a hypoperistalsis syndrome. An anomaly of the TCTN in the muscularis propria disturbs gut-muscle mechanics, and is another cause of gut dysmotility.