High‐resolution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipation

Giorgio, Valentina; Borrelli, Osvaldo; Smith, Virpi V.; Rampling, Dyanne; Köglmeier, Jutta; Shah, Neil; Thapar, Nikhil; Curry, Joseph I.; Lindley, Keith

doi:10.1111/nmo.12016

Cited by 86 publications

(95 citation statements)

References 26 publications

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“…Colonic manometry is used to differentiate between myopathic and neuropathic motility disorders and to identify dysmotile colonic segments amenable for surgery [27,34,35]. Dysmotility of the colon is usually defined by the absence of high amplitude propagating contractions (HAPCs) and in severe cases this abnormality can be used to justify a total or partial colonic resection and/or diversion of the dysmotile colonic segment by means of an ostomy [11,[36][37][38].…”

Section: Colonic Manometry and Surgerymentioning

confidence: 99%

Surgical decision-making in the management of children with intractable functional constipation: What are we doing and are we doing it right?

Koppen

Kuizenga-Wessel

et al. 2016

Journal of Pediatric Surgery

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Section: Colonic Manometry and Surgerymentioning

confidence: 99%

Surgical decision-making in the management of children with intractable functional constipation: What are we doing and are we doing it right?

Koppen

Kuizenga-Wessel

et al. 2016

Journal of Pediatric Surgery

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“…[2] A study of children with severe STC showed that abnormal colonic manometry was associated with histopathological findings involving neurons, ICCs, and smooth muscle. [33] Colonic dysmotility may be due to neurotransmitter imbalance, such as an excess of nitric oxide in the myenteric plexus, which could inhibit contractile activity. [34] However, the role of neurotransmitters remains unclear as multiple studies on a variety of mediators have yielded contradictory results.…”

Section: Neurogenic Constipationmentioning

confidence: 99%

Pediatric enteric neuropathies: diagnosis and current management

Westfal¹,

Goldstein

2017

Current Opinion in Pediatrics

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Purpose of Review Neurointestinal diseases are increasingly recognized as causes of significant gastrointestinal morbidity in children. This review highlights the most common pediatric enteric neuropathies and their diagnosis and management, emphasizing insights and discoveries from the most recent literature available. Recent Findings The embryologic and histopathologic causes of enteric neuropathies are varied. They range from congenital aganglionosis in Hirschsprung disease, to autoimmune-mediated loss of neuronal subtypes in esophageal achalasia and Chagas disease, to degenerative neuropathies in some cases of chronic intestinal pseudo-obstruction and gastroparesis. Increased awareness of the clinical presentation and diagnostic evaluation of these conditions is essential as it allows for earlier initiation of treatment and improved outcomes. Most current therapies, which include medical management, neurostimulation, and operative intervention, aim to minimize the symptoms caused by these conditions. The evidence base for many of these treatments in children is poor, and multi-institutional prospective studies are needed. An innovative therapy on the horizon involves using neuronal stem cell transplantation to treat the underlying pathology by replacing the missing or damaged neurons in these diseases. Summary While recent advances in basic and clinical neurogastroenterology have significantly improved our awareness and understanding of enteric neuropathies, the efficacy of current treatment approaches is limited. The development of novel therapies, including pharmacologic modulators of neurointestinal function, neurostimulation to enhance gut motility, and neuronal cell-based therapies, is essential to improve the long-term outcomes in children with these disorders.

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“…Neuropathological loss within the enteric nervous system (ENS) has been implicated in a wide range of severe gut motility disorders, such as achalasia123, gastroparesis45, slow transit constipation678 and Hirschsprung’s disease (aganglionic megacolon)910, as well as being associated with a number of central nervous system disorders111213. Potential replacement of lost neurons using stem cell replacement is an attractive therapy for such life-limiting disorders.…”

mentioning

confidence: 99%

Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon

et al. 2017

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Enteric nervous system neuropathy causes a wide range of severe gut motility disorders. Cell replacement of lost neurons using enteric neural stem cells (ENSC) is a possible therapy for these life-limiting disorders. Here we show rescue of gut motility after ENSC transplantation in a mouse model of human enteric neuropathy, the neuronal nitric oxide synthase (nNOS−/−) deficient mouse model, which displays slow transit in the colon. We further show that transplantation of ENSC into the colon rescues impaired colonic motility with formation of extensive networks of transplanted cells, including the development of nNOS+ neurons and subsequent restoration of nitrergic responses. Moreover, post-transplantation non-cell-autonomous mechanisms restore the numbers of interstitial cells of Cajal that are reduced in the nNOS−/− colon. These results provide the first direct evidence that ENSC transplantation can modulate the enteric neuromuscular syncytium to restore function, at the organ level, in a dysmotile gastrointestinal disease model.

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High‐resolution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipation

Abstract: PBAUC(1) is increased in multiple colonic segments in neuropathic pediatric STC and constitutes a sensitive and specific biomarker of neuropathy.

Cited by 86 publications

References 26 publications

Surgical decision-making in the management of children with intractable functional constipation: What are we doing and are we doing it right?

Surgical decision-making in the management of children with intractable functional constipation: What are we doing and are we doing it right?

Pediatric enteric neuropathies: diagnosis and current management

Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon

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