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Enteric neuropathy

Autor: Eva-Maria Elkan Elena Ariela Banu Aurel Nechita Mihai Mutică Ginel Baciu Monica Zlati Marcela Câmpean Mihaela Lungu
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Introduction: Enteric neuropathy is included in the wider spectrum of neuropathies autonomy is a subdiagnosed entity in the child but which has major effects on the patient with a medium and severe neurological pathology. If recognized in time, its effects can be reduced thereby improving neurological pathology. Objective: We want to highlight the involvement of the digestive tract as a vital support for the motor and cognitive superior functions in child through the detailed study of the pathophysiological mechanisms that make these connections. Material and methods: We have gone through the classi- cal specialized literature on Pub-med, Academic Google’s specialized websites. There were 90 articles on epidemiology, rare diseases, prognostic treatment pathophysiology. Results: Enteric neuropathy can be caused by a genetic defect that causes both neurological and digestive impairment, and different diagnosis can come into question where touching is purely digestive or predominantly digestive, such as visceral myopathy or VACTERL syndrome, but which may in general cause neurological connection related damage and even psychiatric and endocrine. Conclusions and discussions: Enteric neuro- pathies, although not yet widely known, are diverse by their causes, including rare but commonly encountered, and the current work is an instrument for their easier recognition for increasing the quality of life of affected patients.

Key words: enteric neuropathy, genetic, neurological, digestive.

Taxonomy: Enteric neuropathy within the framework of autonomic neuropathy,it was also called gastrointestinal dismotility but also autonomous ganglionopathy [1]. Currently, the term neural intestinal dysplasia has been replaced by enteral nervous system disganglionis [2]. Epidemiology: Chronic enteral obstruction is 1 / 40,000 alive newborn up to 1 / 100,000 alive newborn. Chronic intestinal pseudoobstruction is one of the most important causes of intestinal distress in children by 15% and in adults by 20% [3]. Pathophysiology: The eneric nervous system consists of 500 million neurons, which are of 14 types, while the glial cells belonging to them are four times more, these cellular structures are organized into two interdependent plexes that exist along the whole intestine, one located in the submucosa and one myenteric (fig. 1).

There are more theories about intestinal disorders.

An incriminated mechanism is the formation of autoantibodies to acetylcholine diene ganglion receptors belonging to the digestive tract, phenomena that bind mainly to the aphasia of achalasia and chronic intestinal pseudoobstructions [1]. The disturbance of the filamine A gene may lead to a series of complicated phonemes such as chronic intestinal obstruction that can be with disorders in the vascular sphere but also with cardiac defects. The filamine gene A is X linked, and the consequence is the damage to the smooth intestinal muscle layers that becomes abnormal but also an abnormal neuronal migration at the intestinal level [5].

In the intestinal ganglia there may be agangliosidosis for Hirschsprung disease on the variable segments of the intestine, submucosal overload of ganglia in infants who have reached a year-old period associated with B-type intestinal dysplasia. In oesophageal achalasis, affection concerns neurons in myenteric plexuses that release nitric oxide and has a relaxing effect on the esophageal sphincter. Another proposed mechanism is the degeneration or loss of enteric neurons which will result in structural impairment as well as functional deficits of the entire enteric digestive system [7]. On the basis of intestinal chronic pseudoobstruction of intestinal dysfunction, the existence of defective cells interstitial. Also, the ACTG2 gene encoding a protein called gamma 2 enteric actin may be involved in the production of this disease [8]. And the intestinal bacterial change plays a special role of certain bacterial imbalances may alter enteric neurotransmission. This is why clinicians and researchers need to pay attention to the use of probiotics and antibiotics associated with a well thought-out diet that will lead to an enteric aneurotransplant adequacy [9].

In 2005, Bäckhed and his team have defined the microbiota that is an ambious symbiotic ecosystem and is composed of bacteria, viruses, fungi and protozoa as well as archaea. The immune constellation of the host, its genetic terrain, and age, play a decisive role in how this microbiota system evolves and how it can influence the functionality of the enteric nervous system, and epigenetic changes mean changes in the way the genes explode but without modify DNA. The microbiota will change the polarization of the primary intrinsec neurons in the intestine, and calbindin-sensitive neurons are also involved in this mechanism. On the other hand, by modulating the expression of the tryptophan- hydroxylase-1 gene, which has the role of limiting the transformation of tryptophanes from food into serotonin, short chain fatty acids, vitamin E antioxidants as well as bile acids can act [9]. Enteric gangliitis is formed primary or secondary: paraneoplasic or due to infections or secondary to neurological affections.An enteric layer is an infiltrate composed of inflammatory and immune cells. These processes will lead to dysfunction of the neurons in the intestine and even to their degeneration, so some of the eneuric neurons will be lost from the intestine due to these processes. Ganglionitis will be affirmed when there are circulating antineuronal antibodies that are directed to certain molecular targets. These attacked molecules are Hu and Yo proteins, as well as neurotransmitter receptors and ion channels [10]. In chronic gastric pseudoobstruction syndrome there is an increased intestinal pressure that will lead to intestinal malabsorption phenomena as well as bacterial translocation phenomena leading to malnutrition and the migration of bacteria into the blood so sepsis (fig. 2).

Diabet mellitus involves various diseases affecting 60-70% of diabetics (peripheral nerves, neuropathy affecting erectile dysfunction,autonomic dysfunction is also expressed at cardiovascular level with changes in heart rate and blood pressure gastroparesis). Neuropathies occurring in various forms of diabetes

and at any age improve when metabolic balance is restored in diabetes, these disorders can disrupt the patient’s sleep [13]. In diabetics, the development of neuropathy with various disorders is somewhat predictable if triglycerides are elevated if the index body mass is increased if smoking is present (which also begins with children in lashes and the hypertension (already present in 10% of young people either known or unknown) [14].

Lupus can be incriminated because of the changes that induce gastrointestinal symptoms in 50% of patients. These manifestations may be enteropathy with protein loss, intestinal pseudoobstruction but also hepatic damage as well as pancreatitis [15]. In lupus, it can be associated with intestinal pseudoobstruction and hepatobiliary dilatation without obstruction as well as ureterohydronephrosis without calculus by a mechanism of damage to smooth muscle motility [16].

Siclemia can sometimes be incriminated in generating digestive complications such as intestinal pseudoobstruction [17].

Hirschrpung disease occurs with a frequency of 1/5000 births and its symptoms are the child’s inability to remove meconium within the first 24 hours, which subsequently leads to abdominal distension, unable to feed as well as vomiting. There are some diseases that associate Hirschprung- type changes such as Down syndrome that has these changes in 10% of patients, they also occur in Haddad’s syndrome, but such changes are also found in Mowat-Wilson’s syndrome [6]. Aggliosidosis from Hirschprung disease is not always present along the entire intestinal tract, it may be partial and then it is more common in the rectosigmoid segment [2].

Esophageal achalasia is estimated to be 0.18

/ 100.00 cases and leads to esophageal motor dysfunction followed by dysphagia, regurgitation as well as severe retrosternal discomfort and weight loss. It is divided equally by gender and is diagnosed at about 10.9 years. Gastroparesis occurs in the context of viral infections (18%), surgical procedures (12.5%), mitochondrial diseases (8%) and diabetic (2% -4%) [18].  After viral infections, gastroparesis may be severe, infections with bacteria and ulcers may occur, which in turn can give pulmonary embolisms leading to death [19] (fig. 3).

Spinocerebellar ataxia with infantile onset transposed autosomal recessive has a profound clinical picture in adolescence with profound hearing loss that associates sensory axonal neuropathy with optic atrophy but also dysfunction of the autonomic nervous system and on female pacients it is highlighted with hypogonadotrophic hypogonadism [20].

Myotonic dystrophy can often associate with chronic intestinal pseudoobstruction in the adult, and in the child is much rarer and may be caused by association in this pathology with deficiency of smooth muscle α-actin at the level of the external muscular layer of the ileum and in the colon can be manifested by eosinophilic plexitis and eosinophils can infiltrate and musculature of the colon [21].

Mutations of filamine A are found in women more frequently because men do not usually survive this disease, being X linked. The changes that occur are periventricular nodular heterotopia epxplifiable by the fact that the mechanism of neuronal migration is affected, cardiac complications, especially valvulopathies explained by thickening of valves but also by widening of blood vessels, thrombocytopenia with anisocytosis and abnormal distribution of granules at their level but also Ehlers syndrome is associated with this dysfunction. In the digestive tract, dysfunctions are intestinal malnutrition and intestinal pseudoobstruction that helps diagnose whether they are considered by the clinician [22].

Mitochondrial gastrointestinal mitochondrial encephalomyopathy (MNGIE) is rare, and its transmission is autosomal recessive. Mutations are related to thymidine phosphorylase, therefore thymidine and deoxyuridine will increase which are toxic and will affect mitochondrial AD activity [23]. MINGE syndrome may begin with an atypical anorexia. The average diagnosis time from the first symptoms is 12 years. The diagnosis is made by adding the following criteria: an increase in lactic acid in the blood but without a modified pH, cerebral MRI modified with leukoencephalopathy and without obvious symptoms. Direct MINGE criteria are less than 10% decrease in thymidine phosphorylase activity in leukocytes, as well as plasma thymidine elevation> 3μmol / L with plasma deoxyuridine levels> 5μmol / L), and a positive molecular gene test for the TYMP gene [24].

Mitocondropathy is an important cause in children affected by rare diseases. They involve 15% of cases of gastrointestinal symptoms. In the case of MELAS syndrome, it is associated with mitochondrial A3243G DNA mutation. The associated digestive symptoms are bloating, dysphagia, recurrent vomiting and anorexia [12]. When the patient has such a mutation, the ability to develop chronic choroidal pseudoobstruction is greater if he or she already has a heart attack and a small body mass index [25].

Fabry disease is a lysosomal disease and is linked by chromosome X and, after the most recent data, affects about 1/4000 neonatal children. Digestive symptoms include nausea, abdominal pain, diarrhea, and the feeling of satiety that occurs early. Globotriaosylceramides (GL-3) that localize in lysosomes accumulate in the patient’s cells because the α-Gal enzyme in the lysosomes of the patient is deficient. Pathophysiological processes such as tissue inflammation due to local ischaemia and repairing fibrosis will be followed [3].

Microcholon syndrome associated with intestinal hypoperistalism and enlarged bladder. Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is present at birth and is characteristic loss of smooth muscle contraction in the bladder and intestine. The genes that are due to this syndrome are: ACTG2, MYH11, and LMOD1 (fig. 4).

Enzymes that are inflamed are myosin light chain kinase that has three long-lasting isoforms that are not characteristic of a shorter muscle but of smooth muscle and a very short one called telokina 17 [26]. In these patients with the ACTG2 mutation heterozygote missense variants [27] were found. It was thought that the transmission of the syndrome was only autosomal recessive, but autosomal dominant variants were also found in this syndrome [28]. A dominant autosomal variant also involves biliary dysfunction by affecting the gallbladder musculature contract [29]. In this syndrome it may appear and migrate [30]. Functional gastrointestinal obstruction can be associated with Prune-Belly syndrome as well as with external ophthalmoplegia, and another shock is the Barett esophagus. MMIHS can also be associated with trisomy 18, with cardiac rhabdomyomas and deletion 15 q 11 [31]. Patients with this syndrome often require parenteral nutrition, and later transplantation of multiple organs is proposed [32]. Bladder distention can be done with CICC-clean intermittent catereresiation, or a vesicostomy can be done, adding antibiotic prophylaxis, but only if urinary infections are common. Similarly, these gastrostomy or ileostomies as well as total parenteral nutrition are often done, the sequencing of these therapies increasing the quality of the patients and the long-term survival of better patients [33].

Treacher Collins Syndrome has a spectrum of mutations comprising (TQF1) (5q32-q33.1) but also polypeptides D and C of ARN POLR1D [13q12.2], POLR1C [6p21.1] these mutations ultimately lead mouse to agangalionosis of the colon and can explain the association of this syndrome with chronic intestinal pseudoobstruction [34].

Ellis-van Creveld syndrome (EVC) is a rare recessive autosomal sindroma and associates with hypoplastic nail, polydactyl and acondrodisplasia. Cognition is usually normal in these children. Usually intestinal function is not impaired, but when it is associated there may be severe impairment of development [35].

Ogilvie’s syndrome is acute colon pseudoobstruction and rarely occurs in children, they accuse abdominal pain and have a large abdomen, painfully tympanic, have nausea and vomiting, but preserve intestinal peristalsis and imagistically caracterize through a very large dilation of the colon but it is obstruction without an obvious obstructive colonic. This syndrome may also occur after kidney transplantation in children [36].

Ogilvie’s syndrome may be caused by cytomegalovirus infection [37].

Kawasaki’s disease is also associated with intestinal pseudo-obstruction syndrome [38]. Sometimes this malady can, by this mechanism, mimic acute chirugical abdomen [39].

Amyloidosis due to multiple myeloma may mislead the diagnosis in the case of intestinal pseudobstruction in this constellation and may imitate ascites which will easily give diagnostic errors [40].

A vast majority of viruses give neuropathies with sequelae that can spread over days and even years. Viruses coxackie, echo, and traces of measles can also install this enteral neuropathy that we can also name enteropathy.

Campylobacter jejuni may cause gastroenteritis and cause complications such  as  Guillain Barre Syndrome or Miller Fisher Syndrome. Antiganglioside antibodies are produced on nonobial diabetic mice and the interleukin involved is IL 10 [41].

Campylobacter jejuni virus can cause intestinal pseudoobstruction and progressive multifocal leukoencephalopathy in patients with renal transplant.This can be demonstrated by PCR for this virus from the cerebrospinal fluid and blood [42].

Varicella virus infection can cause gastric or intestinal perforation by ulceration and intestinal pseudoobstruction. The virus is highly infectious in vivo but in vitro only transmits the cell to the cell. In adults or immunocompromised patients this infection can cause death. Virsul enters the human respiratory tract and then gets the lymphoid tissue and the tonsils. His target is T lymphocytes, and the infection goes to the skin. In the basal cells of the epidermis. The enteric nervous system does not have direct innervation from the CNS. The varicella zoster virus can cantonize and become latent in the eneric nervous system. Just as the virus reactivates in the nerve dorsal roots of the nerves and the cranial nerves can also react to the eneteric level and lead to enteric shing, as demonstrated by autopsy for Ogilvie syndrome. Certain varicella- zoster DNA fragments encoding computed viral components have been found in the saliva of these patients, and these have been shown to have enteric zoster for patients who have complained of abdominal pain and who have not found a specific cause [43].

HIV infection also reaches the glial cells of the intestine, so inflammation occurs in the intestine, which in turn produces lesions of the enteric neurons and they generate an abnormal intestinal response. There is a key protein in this process called transcriptional transactivator called Tat that mediates neuronal lesions once the HIV virus is released from the glial cells. An important mechanism is altering Na + channels and generating the potential for action. Tat works alongside morphine on enteric neurons, morphine inhibiting the generation of action potential and intestinal motility. Dad helps the virus in the transcriptional rheumatoid and causes greater secretion of cytokines that will amplify inflammation and oxidative processes, thus causing apoptosis. The virus also infects macrophages and lymphocytes in the intestines and the damage to enterocytes due to the virus causes malabsorption. HIV also affects the upper segments of the digestive tract, leading to dyspepsia, nausea and vomiting [44].

There also are iatrogenic cases, which are often silent because the side effects of antipsychotics and central nervous system drugs are not always known. Asthma intestinal pseudoobstruction syndrome can be produced by antidepressants, anxiolytics, phenothiazines and others [12]. Thus, in the case of trihexyphenidyl use, intestinal pseudoobstruction syndrome may occur [45]. In the pathology of rare diseases (but which are not always very rare subdiagnosed) an important cause of mitochondrial disease.A mitochondrial disorder is estimated to exist in 1/5000 patients, and 1/400 has a mitochondrial mRNA mRNA from the mRNA of the leucine gene mitochondrial transcript.

Symptoms: The most common are vomiting, abdominal pain, unexplained diarrhea, growth retardation, malaise, association with various endocrine disorders but also the wider context of a systemic illness should make sure the clinician is careful not to get rid of this diagnosis. Constipation is in most cases functional in the child, but in 5% of cases it can have a severe organic substrate, and 20- 25% of pediatric gastroenterology counseling is due to constipation [2]. Sometimes, long-lasting diareea may appear, having subgenus congenital defects of enterocytes in addition to carbohydrate intolerance and allergy to certain foods [46]. Many pathologies lead to intestinal pseudoobstruction syndrome and many of the tote patients become malnourished, and 1/3 of the adult and 80% of the patients will need home care with aparental adherence (Tab. I).

Diagnosis: The most important diagnostic method is anamnesis and “think about”, followed by specific diagnostic tests for detecting digestive tract malfunction, as well as specific tests for each of the suspected particular diseases. All patients will benefit from the usual laboratory examinations blood count, blood glucose, VSH, fibrinogen, urea, creatinine, TGP, TGO, LDH, CK, ammonia analysis that is already required to be used in all pediatric and adult services, of urine. EEG, MRI, or angioIRM, rheumatoid factor, lupus cells, abdominal ultrasound as well as endocrinological examination, ENT exam, gastrioenterological examination, digestive menometry and genetic sequencing also play an important role. The esophagus and esophagus pressure and manometry of esophageal pressure are recorded to detect esophageal achalasis [6]. Anorectal manometry can be practiced at any age and is intended for evaluation of rectangular inhibitor reflex. If this reflex is absent, the patient has Hisrchrpung disease, but rectal biopsy remains the gold standard for a precise diagnosis [2].

For intestinal pseudoobstruction syndrome, abdominal tomography is also practiced, but colonoscopy is also attempted to exclude mechanical obstruction or to decompress the dilated colon [48]. Calprotectin can be dosed to help discriminate congenital defects of enterocitabines or inflammatory causes of diarrhea prolonged [46]. Genetic testing should be recommended by a geneticist who will encourage the family and shorten the search for often exhausting searches for the family but also for medical staff.A simple case-by-case analysis is the glutamine / glutamate ratio that may soon become readily available if it enters the clinical thinking routine, if this ratio is Gln / Glu <7.04, chronic intestinal pseudo-obstruction may occur [47].

Another analysis is Spectrophotometry using the Maldi-TOF method or another known system is Burker Daltoni, however, detecting the fungal species with which the intestine is colonized [49].

Scintigraphy and intestinal biopsy are other valuable analyzes to detect specific pathology. RMN is a useful method for detecting chronic intestinal pseudoobstruction and is not invasive [11]. There is another test called human-albumin scintigraphy

-99 m Tc HAS- that reflects the hypoalbumineamia from enteric disease in lupus with protein loss. Also for digestive lupus is a fecal clearance test of alpha-1 antitrypsin [15]. Methods Histochemical are very important used to detect acetilconlinesterazei that aid in the diagnosis of disease Hirschchprung, the latter are particular colorations such as Masson’s Trichrome stain which is helpful in myopathies enteric that are bazapseudoobstrucţiiei intestinal and methods of immunohistochemical such as c-Kit or PG 9.5 determining causes enteric neuropathy accompanied by pseudo [50] the methods histochemical distinguish between Hirschsprung’s disease and other syndromes of intestinal pseudo- obstruction, which is later used in therapeutic strategies to be applied [51].

Electrophysiology studies are conducted on the patients with peripheral nerve damage and can also be of value in the therapy of these disorders, guiding the improvement under a particular therapy. Thus, in the case of MINGE syndrome – gastrointestinal mitochondrial microscopy, measurements are made at the median and peroneal nerve where stabilization of F wavelength latencies and nerve conduction velocities in sensory nerves and motors after stem cell transplantation have been observed in these patients [52].

Prenatal diagnosis is a gold standard that can be difficult to achieve in many diseases, but it is also possible that pre-natal diagnosis of pre- natal dysmotility as well as microcolon syndrome associated with intestinal hyperopia and enlarged urinary bladder due to the increased bladder ultrasound [26]. Microclone syndrome associated with           hypoperistaltica      and          increased                         unyrcular bladder can be found prenatal in 63% of cases [33]. Differential diagnosis: it is done with esophageal atresia, which has 1/3500 live births. The symptoms of achalasia consist of severe gastroesophageal reflux, esophagitis, but dysphagia is also present, esophageal        dismoilitis, low                 weight gain     and respiratory infections as well as tracheomalacia and low tolerance. The esophageal atresia is two-way: a break that is not long and a long interruption that is defined to be greater than the stretch of two vertebral bodies or also 4-6 cm long. The esophageal dysmotility is often associated with esophageal atresia in children, through the dysfunction of the esophagus’ eneteric system either through its complete disappearance. Signal genes such as Ret

/ GDNF and SOX10 as well as endothelin 3 are implicated in the genesis of the esophageal enteric system. Esophageal atherosclerosis may also occur within the framework of complex malformative syndromes such as VACTERL comprising the involvement of three body systems on vertebrae in associations with cardiovascular and tracheal effects along with esophageal, renal and limb damage. Tracheoesophageal fistula occurs in this syndrome in 50-80% of the cases. Besides the pharmacological and chisrugic classical therapies gradually make new and novel therapies with stem cells in this affection and the autologous glands are introduced by endoscopic methods from other regions of the digestive tract with the help of genetic engineering that multiplies them and then introduces them to their desired location [53]. There is also a specific pathology of visceral myopathy.

A cause of intestinal pseudoobstruction is mesenteric ganglionitis by infiltration with eosinophils that may be present in the child but immunoshistochemical CD4 positive lymphocytes and a change in the expression of fibrillary protein in the affected plexus [54].

Other pathologies involved may be malignancies, mesenteric ischemia, energy of scleroderma, intestinal irritation that give intestinal insufficiency, which is of several degrees, and that of thymus III already requires parenteral nutrition [55].

Joint immunodeficiency is also associated with intestinal pseudoobstruction syndrome and should not be missed [56]. There is a protoncogenic RET gene that may present a RET R114H mutation that occurs both in patients with Hirschprung disease and those with intestinal pseudoobstruction with no other causes. This mutation in this gene affects globally the intestinal motility that it alters [57]. Ascaris lumbricoides is a cause of rare intestinal obstruction in children from undeveloped countries. In developed countries obstruction is mimicked by intestinal adhesions. It causes bloody vomiting that will cause us to think about the ileus. The bile collar and ileus given by Ascaris can also be caused by a single worm, but this and pathophysiology is rarely possible because it is positioned at the level of Vater’s ampoule. The frequency of this helminth in humans increases in tropical and subtropical countries. In addition to direct mechanical obstruction, there is a mechanism in which Ascaris secretes neurotoxins that will cause narrow bowel contraction and will give bowel obstruction [58].

Aerophagia is a functional disorder consisting of repeated swallowing accompanied by abdominal distension and flatulence. It can imitate gastroparesis but also the megacolon and sometimes overlaps with intestinal pseudoobstruction as symptomatology. It is more common in children with mental retardation. Functional aerofagy is present in most children, while the pathologic is present in 8m8% in children with mental retardation. Verbalizing is a method of unleashing copies of this habit [59].

Ethicalconsiderations:Someofthesepathologies fall into wider degenerative pathologies that can lead to death as well. They are called life-limiting diseases, yet their knowledge and dissemination of information has ethical dimensions, helping the specialist to create the best conditions for the patient possible with the knowledge and equipment at one time in a hospital [60]. Another sensitive issue is the sometimes caustic aspect of these children given by these pathologies, and then their erroneous aspect can be attributed to inadequate parental care if the environment from which the child comes is disadvantaged, leading to erroneous judgments on the part of the examiner that may unnecessarily cut off social inquiries or from the very part of the persons authorized to carry out these investigations, the ambiguity of the symptoms presented by the child as well as the compliance with the treatment should be weighed carefully, and such problems were detected in 455 patients with intestinal pseudoobstruction syndrome, which is not yet well which is outlined for clinicians, and therefore errors can be made in assessing the whole child’s problem [61]. Once a genetic disorder is known to a parent, it is necessary to screen the family for genetic counseling [62].

Complications: are direct and indirect. Direct causes are neuropathy itself as a process such as alnutrition, hydroelectrolytic imbalances, endocrine disorders, mental and growth retardation, congestive disturbances, retardation of motor development. Renal complications can be redundant and alarm signals will point renal acidosis, the presence of hydroelectrolytic imbalances, but also the likelihood of overloading with liquids through an infrequently driven infusion regimen, and the uremia with its redundant effects. The deaths that occurred after intestinal transplantation were multiple organ failure due to sepsis favored by intestinal pathology in general, then cerebral edema that can complicate the situation of an intestinal post-transplant patient as well as heart failure that can also lead to multiple organ failure [ 63].

There are also indirect complications as a result of treatments applied to the background, adverse drug reactions or medical treatment reactions such as Mucorvelutinosus infections from catheters used for parenteral nutrition [64].

Parenteral nutrition leads to infections and the average time of parenteral nutrition was 2.9 years in one study and the casteter infection rate was

2.7 / 1000 days of catheter use [65]. Another germ of catheters is Dermacoccus barathri. It is a germ belonging to the Actinomycetes family and is present on human skin and water. [66] A complication of parenteral nutrition is the lack of iodine that can then be manifested with thyroid and gouty disorders as alcohol-based products are used to disinfect the skin and because lipid intake is altered [67].

Gynecological complications in adolescent girls with a neurological or neuromuscular pathology also involve uterine involvement in some cases. Collaboration with centers of expertise prevents diagnostic errors because all interventions are guided by a multidisciplinary team that coordinates nutritional, medical or surgical intakes [68].

Treatment: New directions in the management of enteral neuropathy are mainly related to a new conception of what needs to be adjusted, thus adjusting the weight at the age of the affected children,rather than the chronological age.Important to total parenteral nutrition is the calculation of the nonprotective energy received [69]. For gastroparesis, the use of erythromycin is used as a prokinetic agent and acts as a motilin receptor agonist and thus improves antroduodenal coordination [18]. Helot myotomy is practiced in 85% of cases for esophageal achalasis or periodontal endoscopic myotomy for the same condition [6]. In intestinal pseudoobstruction, the nutritional support of the child must be calculated by a specialist, especially since this aptology often requires parenteral nutrition. Drug treatment aims to reduce excessive bowel colonization in order to avoid sepsis and also to catch up with normal intestinal propulsion [70]. Chronic intestinal pseudoobstruction seeks laxatives, prokinetics, but also natural medicines or teas but does not always give the desired results. For chronic intestinal pseudoobstruction syndrome, percutaneous endoscopic gastrojejunostomy can be an elegant solution and the tube used is easier to suck over the ileus tube [11].

For pseudoobstruction, metoclopramides and domperidones are still in use, but they caution because of neurological and cardiac adverse effects. Octreotide a somatostatin analogue is very rarely used in children [18]. A good response to Octreotide is estimated to be ≥10 cc / kg / day of increasing parenteral nutrition [71]. For intestinal pseduoobstruction, pyridostigmine may be relieved to relieve symptoms [72]. Piridostigmine increases the level of acetylcholine in the neuromuscular junction and causes the contraction of smooth muscle. Doses are 0.25-2.0 mg / kg / day and side effects can be abdominal cramps that pass if treatment stops immediately [73]. In Japan, the medicinal plants used for gastric pseudoobstruction are called Kampo, and Mosapride in Japan is used for the same affection [74]. Chronic intestinal obstruction requires cervical correction in 58% of cases and the average time to develop an opinion on postoperative progression is

7.4 months [75]. Hemodialysis was also attempted to remove toxic metabolites such as MINGE syndrome where the accumulation of thymidine and deoxyuridine is fatal and this method only decreases them for the moment but does not influence the progression of the disease [23]. On the other hand, there are situations when chronic choroidal osteoarthritis syndrome is approached with unnecessary surgical maneuvers when the cause of this syndrome is not recognized as is the case with Fabry disease. But for this disease there is enzyme replacement therapy, and if the disease is discovered in time, the enzyme stops the progression of the disease [3]. In colon pseudoobstruction syndrome called Ogilvie S neostigmine syndrome may be beneficial leading to the disappearance of symptoms [36]. On the other hand, in Hirschrpung disease, the resection of the agangalosidosis is the gold standard, but the promising fact is that it falsifies in the experimental phase and the treatment with stem cells and in this disease [2]. Currently, drug therapies and even chisrugic techniques are still limited in the long-term resolution of these devastating diseases. New therapies that consist of the transfer of stem cells to replace enteric cells [76] are also attractive.

These researches are currently under way in the rat but human therapies for gastrointestinal mitochondrial encephalomyopathy (MINGE) have been started and allogeneic stem cells are transplanted to make the enzyme thymidine phosphorylase function again. The prognosis depends on antigenic matching for human leukocytes, which should be 10/10 versus <10/10, but the disease status is also important as the present hepatic damage as well as the history of intestinal pseudoobstruction in a particular patient. [52]. The cells used for transplantation are enetric stem cells that are present both in the human ebmrion and the adult intestine. Human murine and human cells were used for agglutination colon and the investigations reached both in vitro and in vivo. Loss of nerve nitric synthase nNOS is implicated in the genesis of many diseases that also have enteric neuropathy such as esophageal achalasis as well as hypertrophic pterygium stenosis as well as diabetic and idiopathic gastroparesis, Hirschhcprung disease [77]. Patients with parenteral nutrition are followed at home by nurses, physicians, but at the same time laboratory tests will be done weekly [78]. It is also promising that intestinal transplantation saves the life of the patient and increases the quality of life of the patients to which it is applied. It is complicated by intestinal ischemia, post-transplant volvulus, splanchy thrombosis that may occur and secondary Crohn’s disease, pseudobstruction syndrome, but also enterocolitis or graft rejection. Mortality is still very high postoperatively [79]. After vitamin B12, vitamin B12 needs to be supplemented because of the deficiency of this vitamin in 38% of these children and the doses are either 250 mcg per bone or 1000 mcg intramuscularly one injection per month.

Deficiency of this vitamin in the child’s body leads to megaloblastic anemia but also to neuropsychiatric damage       and      demyelination, which in turn leads to peripheral neuropathy [80]. After the enterocistoplasty, vitamin B12 needs to be supplemented because of the deficiency of this vitamin in 38% of these children and the doses are either 250 mcg per bone or 1000 mcg intramuscularly one injection per month. Deficiency of this vitamin in the child’s body leads to megaloblastic anemia but also to neuropsychiatric damage and demyelination, which in turn leads to peripheral neuropathy [80]. The administration of popstopiloral enteral nutrition means feeding to the duodenum or jejunum when the patient has superior digestive tract obstructions or has a pancreatic disorder or has gastric dismoilitis leading to intestinal pseudoobstruction and also when there is gastroesophageal reflux sever with the risk of aspiration of food and liquids in the lung [81]. New visions of intestinal affections and their relationship to neuropsychia and neuropsychology. Recent research shows that 2/3 of our immunity is managed by the intestine and many of the children with digestive tract disorders may suffer as adults as a consequence of disorder. In the adult life to correct these disorders, more bold therapies such as biofeedback can be followed, but at the same time, it returns to some elements of physiology, starting with the position of defecation, which is the most natural one when the intestine does not suffer from cadaverism, and constipation and secondary autonomic impairment they appear. Substances produced in the brain are also found in the gut locally, for example in the case of serotonin, 95% is produced in the intestine. The vagus nerves orchestrates our inner life being the telephone line between the digestive tract and the brain [82].

The prognosis of intestinal pseudoobstruction is good ad vitam but survival is affected by parenteral nutrition that may sometimes last longer, and therefore the quality of life of patients is impaired.83 The prognosis of intestinal pseudobstruction may, however, be mitigated by a mortality ranging from 10 to 32% [84].


In pediatric neurology there is still no consensus on the palliative care of neuroscientists. These include parenteral nutrition. The authors of a study have shown the need to monitor the laboratory parenteral nutrition in these children. There is a need to create a group of experts abroad already existing these protocols.

  1. Mukaino A, Minami H, Isomoto H, Hamamoto H et. col. An- ti-ganglionic AChR antibodies in Japanese patients with motility disorders.J Gastroenterol. 2018; 15-22
  2. Gfroerer S, Rolle Pediatric intestinal motility disorders. World J Gastroenterol. 2015 Sep 7; 21(33): 9683–9687]
  3. Politei J, Durand C,Schenone AB,Torres A et col. Chronic intes- tinal pseudo-obstruction. Did you search for lysosomal storage di- seases? Mol Genet Metab Rep. 2017; 11: 8–11.]
  4. Burns AJ, Goldstein AM,Newgreen DF, Stamp L.White paper on guidelines concerning enteric nervous system stem cell therapy for enteric Dev Biol. 2016; 417(2): 229–251
  5. Jenkins ZA, Macharg A, Chang CY, van Kogelenberg M et. col. Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss-of-function filamino- pathies.Hum Mutat.2018 ; 39(1): 103-113
  6. Westfal ML, Allan M. Goldstein AM. Pediatric enteric neuro- pathies: diagnosis and current management. Curr Opin 2017 Jun; 29(3): 347–353
  7. Goldstein AM, Thapar N, Karunaratne TB, De Giorgio R3. Clini- cal aspects of neurointestinal disease: Pathophysiology, diagnosis, and treatment. Dev Biol. 2016; 417(2): 217-28
  8. Matera I, Rusmini M, Guo Y, Lerone M. Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction.Eur J Hum Genet. 2016; 24(8): 1211–1215]
  9. Savidge TC.Epigenetic Regulation of Enteric Neurotransmission by Gut Bacteria.Front Cell Neurosci.2016; 9: 503
  10. De Giorgio R, Guerrini S, Barbara G, Stanghellini V Inflamma- tory neuropathies of the enteric nervous system.Gastroenterology. 2004;126(7):1872-83
  11. Ohkubo H, Inoh Y, Fuyuki A, Nakajima Chronic intestinal pse- udo-obstruction. Nihon Rinsho. 2015; 73(5): 875-83
  12. Suzuki J, Iwata M, Moriyoshi H,Nishida S et col. Familial Perni- cious Chronic Intestinal Pseudo-obstruction with a Mitochondrial DNA A3243G Mutation. Intern Med. 2017; 56(9): 1089–1093.
  13. Ghid medical pentru îngrijirea pacienţilor cu diabet zaharat 11.02.2014 / Ministerul Sănătății de-practica-medicala/ghid-medical-pentru-ingrijirea-pacientilor- cu-diabet-zaharat.htm
  14. Tesfaye S, Chaturvedi N, Eaton SE, Ward JD et. col. Vascular risfactors and diabetic neuropathy.N Engl J Med. 2005;352(4):341- 50
  15. Li Z, Xu D, Wang Z, Wang Y et Gastrointestinal system invol- vement in systemic lupus erythematosus.Lupus. 2017;26(11):1127- 1138
  16. Jin P, Ji X, Zhi H, Song X et col.A review of 42 cases of intestinal pseudo-obstruction in patients with systemic lupus erythematosus based on case reports.Hum Immunol. 2015;76(9):695-700
  17. Knorr M, Bienemann K, Walde G, Kaufhold A et. col. A massive intestinal vaso-occlusive crisis or “girdle syndrome” in a 6-year- old boy observed as a first manifestation of sickle cell Klin Padiatr. 2014; 226(6-7): 372-4
  18. Ambartsumyan L, Rodriguez L.Gastrointestinal Motility Disor- ders in Children.Gastroenterol Hepatol (N Y). 2014; 10(1): 16–26
  19. Lobrano A, Blanchard K, Abell TL, Minocha A Postinfectious gastroparesis related to autonomic failure: a case Neurogas- troenterol Motil. 2006 ;18(2):162-7
  20. Lönnqvist Infantile-Onset Spinocerebellar Ataxia.SourceGene- Reviews® University of Washington, Seattle; 2009
  21. Pelizzo G, Calcaterra V, Villanacci V, Mura GB et col.Myotonic dystrophy type 1 and pseudo-obstruction in a child with smooth muscle -actin deficiency and eosinophilic myenteric Turk J Gastroenterol. 2018 Mar;29(2):226-229
  22. Hirotsugu Oda, Tatsuhiro Sato, Shinji Kunishima,Kenji Naka- gawa et col. Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function.Eur J Hum Genet. 2016; 24(3): 408–414
  23. Röeben B, Marquetand J, Bender B, Billing H et Hemodialysis in MNGIE transiently reduces serum and urine levels of thymidi- ne and deoxyuridine, but not CSF levels and neurological function. Orphanet J Rare Dis. 2017; 12: 135
  24. Danjou M, Guardia D, Geoffroy PA, Seguy D,Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE): When and how to suspect it in front of an atypical anorexia nervosa? En- cephale. 2016;42(6):574-579
  25. Shiau Ng Y, Feeney C, Schaefer AM, Holmes CE et col. Pseu- do‐obstruction, stroke, and mitochondrial dysfunction: A lethal combination. Ann Neurol. 2016 Nov; 80(5): 686–692
  26. Halim D, Brosens E,Muller F, Wangler MF et Loss-of-Func- tion Variants in MYLK Cause Recessive Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.Am J Hum Genet. 2017 Jul 6; 101(1): 123–129
  27. Halim D, Hofstra RM, Signorile L, Verdijk RM et col. ACTG2 variants impair actin polymerization in sporadic Megacystis Mi- crocolon Intestinal Hypoperistalsis Syndrome. Hum Mol Genet. 2016 Feb 1;25(3):571-83
  28. De Sousa J, Upadhyay V, Stone Megacystis Microcolon Intesti- nal Hypoperistalsis Syndrome: Case Reports and Discussion of the Literature.Fetal Diagn Ther. 2016;39(2):152-7
  29. Klar J, Raykova D, Elisabet Gustafson E,Tóthová I.Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution.Eur J Hum Genet. 2015; 23(12): 1679–1683
  30. Pandav N, Gupta D, Ingle M, Sawant Megacystic microcolon intestinal hypoperistalsis syndrome with mydriasis in a male child. Trop Gastroenterol.2015;36(3):211-2
  31. Wangler MF,Gonzaga-Jauregu C, Gambin T, Penney S et col. Heterozygous De Novo and Inherited Mutations in the Smooth Muscle Actin (ACTG2) Gene Underlie Megacystis-Microcolon- Intestinal Hypoperistalsis Syndrome. PLoS Genet. 2014; 10(3): e1004258
  32. Soh H, Fukuzawa M, Kubota A, Kawahara H et col. Megacys- tis microcolon intestinal hypoperistalsis syndrome: A report of a nationwide survey in J Pediatr Surg. 2015; 50(12): 2048-50
  33. [Wymer KM, Anderson BB, Wilkens AA, Gundeti MS. Mega- cystismicrocolon intestinal hypoperistalsis syndrome: Case series and updated review of the literature with an emphasis on urologic management. J Pediatr Surg. 2016 Sep; 51(9):1565-73
  34. Giabicani E, Lemale J, Dainese L, Boudjemaa S et col. Chronic intestinal pseudo-obstruction in a child with Treacher Collins syndrome.Arch 2017 Oct;24(10):1000-1004
  35. Iwakura H, Fujii K, Furutani Y, Takatani T et col. Ellis-van Cre- veld syndrome associated with chronic intestinal pseudo-obstruc- tion. Pediatr Int. 2016; 58(1): 64-6
  36. Mier EEA, Díaz PT, Fernández OSJ, Mier SG et col. Acute colo- nic pseudo-obstruction (Ogilvie syndrome) post-renal transplant Bol Med Hosp Infant Mex. 2016; 73(4): 250-255
  37. Charatcharoenwitthaya P, Pausawasdi N, Pongpaibul A.Education and Imaging: gastrointestinal: Ogilvie’s syndrome: a rare com- plication of cytomegalovirus infection in an immunocompetent patient.J Gastroenterol Hepatol. 2014;29(10):1752.
  38. Kapoor S.Kawasaki’s disease: an often overlooked cause of in- testinal pseudo-obstruction in children.Virchows Arch. 2015 Nov;467(5):619-20
  39. Trapani S, Montemaggi A, Simonini G, Calabri GB,Surgical ab- domen with intestinal pseudo-obstruction as presenting feature of atypical Kawasaki disease.J Paediatr Child Health. 2016;
  40. Milivojevic V, Stojanovic M, Rankovic I, Micev M Multiple Mye- loma Associated Intestinal Amyloidosis: Intestinal Pseudoobstruc- tion Falsely Considered as an Rev Recent Clin Trials. 2018 Jan 31;13(1):79-81]
  41. St Charles JL, Bell JA, Gadsden BJ, Malik A et col.Guillain Barré Syndrome is induced in Non-Obese Diabetic (NOD) mice following Campylobacter jejuni infection and is exacerbated by antibiotics.J Autoimmun. 2017 Feb;77:11-38]
  42. Burke MT,Trnka P, Walsh M, Poole LProgressive multifocal leuko- encephalopathy with gastrointestinal disease in a pediatric kidney transplant recipient. Pediatr Transplant. 2013 Aug;17(5):E119-24
  43. Gershon AA,Gershon MD.The Jeremiah Metzger lecture Vari- cella Zoster Virus: Fromoutsideto inside.Trans Am Clin Climatol Assoc. 2016; 127: 282–299
  44. Galligan JJ, HIV, opiates and enteric neuron dysfunction. Neuro- gastroenterol Motil. 2015; 27(4): 449–454
  45. Begbie F, Walker G, Kubba H, Sabharwal A.Acute colonic pseu- do-obstruction in a child taking trihexyphenidyl for drooling: Pre- scribers beware.Int J Pediatr Otorhinolaryngol. 2015;79(6):932-4
  46. Hizarcioglu-Gulsen H, Saltik-Temizel IN, Demir H, Gurakan F et col.Intractable diarrhea of infancy: 10 years of experience.J Pe- diatr Gastroenterol 2014 Nov;59(5):571-6
  47. Yan JK, Zhou KJ, JH, WuO QQ et col. Urinary glutamine/gluta- mate ratio as a potential biomarker of pediatric chronic intestinal pseudo-obstructionOrphanet J Rare Dis.2017; 12: 62
  48. Lee KJ,Jung KW,Myung SJ, Kim HJ,Kim NY,The Clinical Cha- racteristics of Colonic Pseudo-obstruction and the Factors Associ- ated with Medical Treatment Response: A Study Based on a Mul- ticenter Database in Korea.J Korean Med Sci. 2014 May; 29(5): 699–703
  49. Flores-González JC, Guerrero-Lozano I, Pérez-Guerrero JJ, Hernández-González A. First report of invasive fungal disease by Candida fabianii in a non-neonatal paediatric patient, Rev Ibe- roam Micol. 2016;33(1): 48-50
  50. Waseem SH, Idrees MT, Croffie JM.Neuroenteric Staining as a Tool in the Evaluation of Pediatric Motility Disorders. Curr Gas- troenterol Rep. 2015 Aug;17(8): 30
  51. Budianto IR, Obata S, Kinoshita Y, Yoshimaru K et col.Reeva- luation of acetylcholinesterase staining for the diagnosis of Hir- schsprung disease and allied disorders.J Pediatr Gastroenterol Nutr. 2015 May;60(5):606-12
  52. [Halter JP, Michael W, Schüpbach M, Mandel H et col. Allo- geneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain. 2015; 138(10): 2847–2858]
  53. Perin S, McCann CJ, Borrelli O, De Coppi P,Update on Foregut Molecular Embryology and Role of Regenerative Medicine The- Front Pediatr. 2017 Apr28;5:91
  54. Hyekyung Lee, Dongwook Kang, Heejin Kim,1 Byungsun Cho   et col. Unusual Histology of Eosinophilic Myenteric Ganglionitis: A Case Report. J Pathol Transl 2017 May; 51(3): 320–324
  55. Dibb M, Soop M, Teubner A, Shaffer Jet col. Survival and nutri- tional dependence on home parenteral nutrition: Three decades of experience from a single referral Clin Nutr. 2017;36(2):570- 576
  56. Arays R, Goyal S, Jordan KM. Common variable immunodefici- ency, immune thrombocytopenia, rituximab and splenectomy: im- portant considerations. Postgrad Med. 2016 Aug;128(6):567-72
  57. Rossi V, Mosconi M, Nozza P, Murgia Det col. Chronic intestinal pseudo-obstruction in a child harboring a founder Hirschsprung RET mutation. Am J Med Genet A. 2016 Sep;170(9):2400-3
  58. Shuichiro Umetsu, Tsuyoshi Sogo, Kentaro Iwasawa, Takeo Kon- do et col.Intestinal ascariasis at pediatric emergency room in a developed country World J Gastroenterol. 2014 Oct 14; 20(38): 14058–14062
  59. Morabito G, Romeo C, Romano C Functional Aerophagia in Children: A Frequent, Atypical Disorder Case Rep Gastroenterol. 2014 Jan-Apr; 8(1): 123–128
  60. Glasper EA.Upholding Ethical Decision Making in Children With Life Limiting Illnesses.Compr Child Adolesc Nurs. 2017; 40(4): 215-218
  61. J B, E B, K L, H C. et col.OP-8 Social concerns in Children be- ing investigated for chronic intestinal pseudo-obstruction.J Pediatr Gastroenterol 2015; 61(4): 512
  62. Milunsky A, Baldwin C, Zhang X, Primack D et col. Diagno- sis of Chronic Intestinal Pseudo-obstruction and Megacystis by Sequencing the ACTG2 J PediatrGastroenterolNutr. 2017 Oct; 65(4): 384-387
  63. Pineda C, Grogan T, Lin JA, J Zaritsky J et col. The use of renal replacement therapy in critically ill pediatric small bowel trans- plantation candidates and recipients: experience from one center Pediatr Transplant. 2015; 19(4): E88–E92
  64. Kumar M, Jantausch B, Torres C, Campos JCentral Line-Associ- ated Mucorvelutinosus Bloodstream Infection in an Immunocom- petent Pediatric Patient.J Pediatric Infect Dis Soc. 2018;7(2):e55- e57
  65. [Choi SJ, Lee KJ, Choi JS, YangHR et col. Poor prognostic factor in patients with parenterla nutrition-dependent pediatric intesti- nal failure.Pediatr Gastroenterol HepatolNutr. 2016 Mar; 19(1): 44–53]
  66. Takahashi N1, Shinjoh M2, Tomita H1, Fujino A1 et col. Cathe- ter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans. J Infect Chemother. 2015 Aug;21(8):613-6
  67. Mortensen M1, Williamson N2, Davis C2, Kanyu Hsu E3 et Iodine Deficiency in a Parenteral Nutrition-Dependent Adoles- cent With Intestinal Pseudo-Obstruction. JPEN J Parenter Ente- ral Nutr. 2016 Jul;40(5):730-3
  68. Thapar N, Saliakellis E, Benninga MA, Borrelli O Paediatric In- testinal Pseudo-obstruction: Evidence and Consensus-based Re- commendations From an ESPGHAN-Led Expert Group.J Pedi- atr Gastroenterol 2018 Jun;66(6):991-1019
  69. Abi Nader E, Lambe C, Talbotec C,Dong L et A New Con- cept to Achieve Optimal Weight Gain in Malnourished Infants on Total Parenteral Nutrition.JPEN J Parenter Enteral Nutr. 2018 Jan;42(1):78-86
  70. Di Nardo G, Di Lorenzo C, Lauro A, Stanghellini V,Chronic in- testinal pseudo-obstruction in children and adults: diagnosis and therapeutic options.Neurogastroenterol Motil. 2017 Jan;29(1)
  71. Ambartsumyan L, Flores A, Nurko S, Rodriguez Utility of Oc- treotide in Advancing Enteral Feeds in Children with Chronic In- testinal Pseudo-Obstruction. Paediatr Drugs. 2016;18(5):387-92
  72. Choudhury A, Rahyead A, Kammermeier J, Mutalib The Use of Pyridostigmine in a Child With Chronic Intestinal Pseudo-Ob- struction.Pediatrics. 2018;141(Suppl 5):S404-S407
  73. Manini ML, Camilleri M, Grothe R, Di Lorenzo Application of Pyridostigmine in Pediatric Gastrointestinal Motility Disor- ders: A Case Series.Paediatr Drugs. 2018;20(2):173-180
  74. Hashizume N, Yagi M, Ushijima K,Seki Y et col. Pharmacothera- py for pediatric chronic intestinal pseudo-obstruction: Nationwide survey in Japan. Pediatr Int. 2017; 59(4): 467-472
  75. Lee KJ,Jung KW, Myung SJ,Kim HJ.The Clinical Characteristics of Colonic Pseudo-obstruction and the Factors Associated with Medical Treatment Response: A Study Based on a Multicenter Database in Korea.J Korean Med Sci. 2014; 29(5): 699–703
  76. McCann CJ, Thapar N.Enteric neural stem cell therapies for en- teric neuropathies Neurogastroenterol Motil. 2018 Apr 29:e13369
  77. McCann CJ, Cooper JE,Natarajan D,Jevans B Transplantation of enteric nervous system stem cells rescues nitric oxide synthase de- ficient mouse colon.Nat Commun. 2017; 8: 15937
  78. Smith A, Feuling MB, Larson-Nath C, Karls C et Laboratory Monitoring of Children on Home Parenteral Nutrition: A Pro- spective Study.JPEN J Parenter Enteral Nutr. 2016;
  79. Ceulemans LJ, Monbaliu D, De Roover A, Detry O et col. Belgian multicenter experience with intestinal transplantation. Transpl 2015; 28(12): 1362-70
  80. Keenan A, Whittam B, Rink R, Kaefer M et col. Vitamin B12 deficiency in patients after J Pediatr Urol. 2015; 11(5): 273.e1-5
  81. Capriati T, Cardile , Chiusolo F, Torroni F et col. Clinical ma- nagement of post-pyloric enteral feeding in children. Expert Rev Gastroenterol Hepatol. 2015 Jul;9(7):929-41
  82. Giulia Enders Șarmul discret al intestinului . Povestea celui mai subestimat organ al corpului București 2016 Lifestyle Publishing
  83. Muto M, Matsufuji H, Tomomasa T, Nakajima A et col. Pediatric chronic intestinal pseudo-obstruction is a rare, serious, and intrac- table disease: a report of a nationwide survey in Japan.J Pediatr Surg. 2014 Dec;49(12):1799-803
  84. [Yan JK, Zhou KJ, JH, WuO QQ et col. Urinary glutamine/gluta- mate ratio as a potential biomarker of pediatric chronic intestinal pseudo-obstructionOrphanet J Rare Dis.2017; 12: 62].