[How to treat spasticity after stroke ?] / Comment je traite la spasticité après un accident vasculaire cérébral.

Spasticity is a form of hypertonia frequently encountered in patients who suffered from stroke and is a cause of functional limitation, contractures, osteoarticular deformations, pain and wounds. The first-line treatment of focal or multifocal spasticity consists in intramuscular injections of botulinum toxin type A in the muscles concerned, in association with positioning measures and physical therapy. Despite the fact this pathology is common, there is often a delay in the diagnosis, and consequently the treatment, leading to harmful consequences for the patient. In some specific indications, surgery can also be a therapeutic option. Finally, spasticity should be distinguished from other types of hypertonia, e.g. dystonia.

: La spasticité est une forme d'hypertonie, fréquemment rencontrée dans les suites d'un accident vasculaire cérébral. Elle peut être à l'origine de limitations fonctionnelles, de rétractions tendineuses, de déformations ostéoarticulaires, de douleurs et de plaies. Le traitement de première ligne de la spasticité focale ou multifocale repose sur l'injection intramusculaire de toxine botulique de type A dans les muscles entrepris, en association à des mesures de positionnement et à une prise en charge kinésithérapeutique. Malgré la fréquence de cette affection, elle est encore trop souvent reconnue, et donc traitée, tardivement, ce qui aboutit à des conséquences délétères pour le patient. Dans certaines indications précises, la chirurgie a également une place dans l'arsenal thérapeutique de la spasticité. Enfin, la spasticité ne doit pas être confondue avec les autres formes d'hypertonie, comme la dystonie.

Surgical Sphincter Saving Approach and Topical Nifedipine for Chronic Anal Fissure with Hypertonic Internal Anal Sphincter.

PURPOSE: The role of augmented internal anal sphincter (IAS) tone in the genesis of posterior chronic anal fissure (CAPF) is still unknown. Lateral internal sphincterotomy is the most employed surgical procedure, nevertheless it is burdened by high risk post-operative anal incontinence. The aim of our study is to evaluate results of sphincter saving procedure with post-operative pharmacological sphincterotomy for patients affected by CAPF with IAS hypertonia. Methods: We enrolled 30 patients, undergone fissurectomy and anoplasty with V-Y cutaneous flap advancement; all patients received topical administration of nifedipine 0.3% and lidocaine 1.5% ointment-based therapy before and for 15 days after surgery. The primary goal was patient's complete healing and the evaluation of incontinence and recurrence rate; the secondary goal included the evaluation of manometry parameters, symptom relief and complications related to nifedipine and lidocaine administration. Results: All wounds healed within 40 days after surgery. We didn't observe any de novo postoperative anal incontinence case. We reported 2 cases of recurrences, healed after conservative therapy. We didn't report any local complications related to the administration of the ointment therapy; with whom all patients reported a good compliance. Conclusions: Fissurectomy and anoplasty with V-Y cutaneous advancement flap and topical administration of nifedipine and lidocaine, is an effective treatment for CAPF with IAS hypertonia.

Incidence of complications in the management of non-ambulatory neuromuscular early-onset scoliosis with a rib-based growing system: high- versus low-tone patients.

PURPOSE: The purpose of this study is to evaluate whether patients with high-tone neuromuscular early-onset scoliosis have different surgical outcome and complication rate, when compared to patients with low-tone neuromuscular early-onset scoliosis treated with a rib-to-pelvis rib-based dual growing system. METHODS: This is a retrospective cohort study of 67 neuromuscular early-onset scoliosis patients, collected from a multicenter database, treated with a rib-to-pelvis rib-based dual growing system. All patients were divided into two groups: high tone and low tone. Pre-, intra- and postoperative data were compared between both groups. Complications were reported by a standardized system. RESULTS: Twenty-six high-tone and 41 low-tone patients were found homogeneous regarding gender, age at surgery, weight, height, estimated blood loss and surgery time. High-tone group (19/26 = 73.1%) experiences more postoperative complications than low-tone group (22/41 = 53.7%). Most common complications were infection, device migration, death and hardware failure. Permanent abandonment of rib-based growing technique and device removal was required in 21% of high-tone patients (P < 0.001). None of the low-tone patients required abandonment. CONCLUSION: High-tone patients had more complications than those with low tone in management of neuromuscular early-onset scoliosis treated with a rib-to-pelvis rib-based dual growing system. A different surgical approach may be required to treat the high-tone neuromuscular early-onset scoliosis.

Pediatric tone management.

Tone management is one of the primary roles of a pediatric physiatrist. Hypertonicity frequently inhibits normal movement patterns in children with central nervous system lesions but at times can reinforce muscle group firing and be useful for a child's function. Treatment approaches should be individualized based on functional goals, degree of impairment, interference with care, and type and location of hypertonicity. Treatment plans should be created in collaboration with all individuals caring for the child. There are many causes of hypertonicity as well as many nonsurgical and surgical treatments. Historical and current evidence-based treatments are reviewed.

Massive accumulation of 11C-Pittsburg compound B in the occipital lobes of a patient with early-onset dementia accompanied by muscle weakness and hypertonicity.

A 44-year-old woman underwent 11C-Pittsburg compound B (11C-PiB), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), 99mTc-ethyl-cysteinate-dimer single photon emission computed tomography, and magnetic resonance imaging after presenting with progressive dementia, muscle weakness, and hypertonicity. Some of her family members had died of muscle weakness with early-onset dementia of unknown etiology. Neurological and psychological examinations revealed moderate dementia in general fields and muscle weakness in her upper limbs. 11C-PiB PET/CT revealed abnormal accumulations of amyloid in the bilateral occipital lobes, while physiological uptakes of 11C-PiB in areas that normally show high uptake, such as white matter, appeared relatively decreased. Meanwhile, cerebrospinal fluid (CSF) amyloid-ß was decreased, and CSF total and phosphorylated tau proteins were increased. This case may be representative of a new category of amyloid deposition disease characterized by early-onset dementia, muscle weakness, and hypertonicity, or at least, a new uptake pattern of PiB in variant AD.

Muscle hypertonia after permanent focal cerebral ischemia in rats: a qualitative and quantitative behavioral and electrophysiological study.

OBJECTIVES: To examine the level of peripheral muscle resistance after cerebral ischemia. METHODS: A total of 326 healthy male Sprague-Dawley rats were used in the present experiments. We used a modified method to establish peripheral muscle resistance in rat model of stroke, and qualified the recovery of motor functional deficits by behavioral measures and quantified the level of peripheral muscle resistance by electrophysiological test. RESULTS: Neurological score started to go up from day 0, achieved its peak on day 3 (1.49 ± 0.56) and kept at a high level within 10 days after surgery. Compared with 1 day before surgery, both the turn score in corner test and asymmetry score in cylinder test were increased significantly on day 3, day 6 and day 9 after surgery (p < 0.01). On day 6 and day 9 after surgery, the Hmax:Mmax ratio of hemiplegic side of middle cerebral artery occlusion (MCAO) rats was obviously higher than the same side in healthy rat (p < 0.01) and the ratio on the contralateral side of MCAO rats (p < 0.05). CONCLUSIONS: There is a progressive increase in peripheral muscle resistance on day 6 to day 9 after surgery in a rat model of postischemic stroke.

[Etiology and pathophysiology of benign prostate hyperplasia]. / Ätiologie und Pathophysiologie der benignen Prostatahyperplasie.

The pathogenesis of benign prostate hyperplasia (BPH) is still unclear. It is a common disease affecting exclusively humans in its full clinical appearance. There is a broad variety of possible underlying mechanisms which most likely interact in the pathogenesis of the disease: inflammatory processes taking place predominantly in the stroma and inducing proliferation of all tissues within the transitional zone, an imbalance of androgens and estrogens and their receptors, hyperinsulinemia and hypercholesterolemia (metabolic syndrome) as direct promoters of glandular growth and autosomal dominant inheritance. The detrusor muscle responds to the increased outflow resistance with muscular hypertrophy. Decreased compliance of the bladder wall results in voiding difficulties while electric instability of the hypertrophied detrusor muscle and increased recruiting of otherwise silent afferent fibres cause storage symptoms.

Fissurectomy combined with anoplasty and injection of botulinum toxin in treatment of anterior chronic anal fissure with hypertonia of internal anal sphincter: a pilot study.

BACKGROUND: In patients affected by anterior chronic anal fissure (CAAF) with hypertonia of the internal anal sphincter (IAS), the role of IAS hypertonia remains unclear. The aim of this study was to evaluate the efficacy of fissurectomy combined with advancement flap and IAS injection of botulinum toxin in healing the CAAF with hypertonia of IAS resistant to medical therapy. METHODS: Ten consecutive patients were enrolled. Anorectal manometry was performed preoperatively and at 6 months. CAAF with hypertonia was defined as those associated with maximum resting pressure (MRP) values higher than 85 mmHg. All patients underwent fissurectomy and anoplasty with advancement skin flap combined with the intrasphincter injection of 30 UI of botulinum toxin. Complete healing, MRP changes, relief of symptoms and immediate and long-term complications were recorded. RESULTS: Complete healing was observed in all patients within 30 days of the operation. The intensity and duration of pain post-defecation was reduced significantly starting from the first defecation. In all subjects, the preoperative MRP values were significantly reduced at 6 months. One month after surgery, three patients reported anal incontinence, two of them had complained preoperatively. The only postoperative complications were minor. CONCLUSIONS: Fissurectomy combined with advancement flap and intrasphincter injection of botulinum toxin results in complete healing, significant MRP reduction and full relief of symptom in all patients, thus it represents a valid procedure in preventing the occurrence of anal incontinence.

Topical application of isosorbide dinitrate in patients with persistent constipation after pull-through surgery for Hirschsprung's disease.

AIMS: The aim of this study was to evaluate the anal manometric changes and the clinical effects after topical application of isosorbide dinitrate (ISDN) in patients with persistent constipation after pull-through surgery for Hirschsprung's disease (HD). METHODS: We studied 3 children (2 males and 1 female), aged 2, 3 and 5 years respectively, who had undergone the Soave-Boley surgical procedure for HD and who suffered from persistent constipation after operation. We performed a pre- and postoperative anorectal manometry study and we applied ISDN paste (1 mg/kg two times daily) in the anal region for three weeks. All patients were followed-up and re-evaluated at 1, 3, and 6 months. RESULTS: All patients showed an improvement of symptoms, with an average of 4 spontaneous evacuations per week. Prior to the topical treatment, the medium pressure was 115.6 mmHg (range 102 - 130 mmHg), the maximum pressure was 160 mmHg (range 145 - 175 mmHg), and the medium length of the high pressure zone was 1.8 cm (range 1.5 - 2.0 cm). At the 6 month follow-up, the medium pressure was 57.3 mmHg (range 52 - 61 mmHg, a decrease of 54.4 %), the maximum pressure was 98 mmHg (range 88 - 107 mmHg; a decrease of 38.7 %), and the medium length of the high pressure zone was 1.6 cm (range 1.4 - 1.8 cm; a decrease of 11.1 %). CONCLUSIONS: Topical treatment with ISDN is a valid therapeutic alternative to an anal myotomy in patients with persistent constipation after pull-through surgery for HD. However, a greater number of cases and a longer follow-up are necessary to confirm the validity of our experience.

How many uncomplicated male and female overactive bladder patients reveal detrusor overactivity during urodynamic study?

OBJECTIVE: We retrospectively evaluated the incidence of detrusor overactivity (DO) in uncomplicated overactive bladder syndrome (OAB) patients. METHODS: From December 1993 to October 2003, 139 adult patients were referred to an urodynamic clinic for urodynamic evaluation of frequency and/or urinary incontinence. Of these, 50 patients (12 males and 38 females) with urgency, without any overt pathological conditions, were retrospectively evaluated in regard to patient age, storage symptoms, urodynamic parameters, and the presence or absence of DO (DO patients or no DO patients, respectively). RESULTS: The overall incidence of DO was 75% (nine of 12 patients) and 36.8% (14 of 38 patients) in male and female patients, respectively. Two of nine male DO patients and five of 14 female DO patients revealed DO after provocative maneuvers. In male patients, all DO patients were OAB wet. In female patients, 13 of 14 DO patients were OAB wet (92.9%), whereas 17 of 24 no DO patients were also OAB wet (70.8%). Compared with no DO patients, female DO patients revealed statistically significant lower maximum cystometric capacity (P = 0.0139) and lower vesical compliance (P = 0.0002). Although aged 60 years or more was associated with DO in univariate analysis in female patients, any symptoms, even incontinence, were not associated with DO in both sexes. CONCLUSION: It is supposed that, in contrast to male OAB, DO might not be a major underlying cause of uncomplicated female OAB.

Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic detrusor overactivity of spinal origin: results of a double-blind randomized placebo-controlled trial.

OBJECTIVES: To access by a placebo-controlled randomized clinical trial the effect of intravesical resiniferatoxin on the urodynamic parameters of patients with neurogenic detrusor overactivity (NDO) of spinal origin. METHODS: Twenty eight patients with spinal NDO were randomised to receive intravesically 50 nM resiniferatoxin dissolved in 10% ethanol in saline (RTX group) or only the vehicle solution (placebo group). Filling cystometries were obtained in each patient at 1 month and 1 week before and at 1 and 3 months after treatment. In a visual analog scale patients were asked to estimate the discomfort induced by treatment. Patients were also persuaded to fill a micturition chart during the 3 days preceding each cystometry. RESULTS: The RTX and placebo groups were homogeneous in what respects the volume to first involuntary detrusor contraction (FDC, 143+/-95 ml and 115+/-58 ml, respectively, p=0.3) and maximal cystometric capacity (MCC, 189+/-99 ml and 198+/-111 ml, respectively, p=0.8). At the end of the study, mean FDC and MCC in the RTX group, 184+/-93 ml and 314+/-135 ml, respectively were significantly higher than in the placebo group, 115+/-61 ml (p=0.03) and 204+/-92 ml (p=0.02). In the visual analogue scale discomfort caused by treatment was similar. Only 10 patients in the RTX group and 6 patients in the placebo group completed adequately the micturition chart. Mean frequency and urinary incontinence decreased significantly only in the RTX group. CONCLUSIONS: Intravesical RTX is effective in increasing bladder capacity in spinal NDO patients. Such increment might contribute to decrease urinary frequency and incontinence of these patients.

Observations on the function of the female urethra: III: An overview with special reference to the relation between urethral hypermobility and urethral incompetence.

AIMS: To analyze the relation between urethral hypermobility and urethral incompetence, and to summarize the interdependence between maximum urethral closure pressure (MUCP), urethral hypermobility, and urethral incompetence. PATIENTS AND METHODS: A group of 255 patients was selected from a large bank of cases. Inclusion criteria were age 20 years or above, no neurological disease, stable bladder, and no previous incontinence surgery or hysterectomy. The degree of hypermobility (cysto-urethrocele) and the degree of urethral incompetence (abdominal leak point pressure (ALPP)) were determined. Statistical analyses between urethral hypermobility and incompetence were performed with Spearman's correlation and the Jonckherre-Terpstra test. RESULTS: The Spearman's rank correlation test showed a statistically significant relation between urethral hypermobility and the degree of urethral incompetence (P = 0.0049). CONCLUSIONS: The statistically significant relation between urethral incompetence and hypermobility suggests that urethral incompetence will increase as the degree of urethral hypermobility does. Optimal conditions for urinary continence include a high maximum urethral closure pressure, absence of hypermobility, and a low degree of urethral incompetence. This last factor is assured by a strong support underneath the urethra permitting compression of the latter during straining. Failure of the urethral closure mechanism is highly probable with a diminished maximum closure pressure accompanied by urethral hypermobility often associated with a high degree of urethral incompetence. Clinically significant urinary incontinence may appear in many intermediate circumstances between these two extreme states, but stress urinary incontinence is essentially an activity-related phenomenon.

Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions.

OBJECTIVE: To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs). MATERIAL AND METHODS: Fifteen SCL patients suffering from NDO and incontinence were included in the study. The volume of urine leakage during episodes of incontinence was quantified, and filling cystometry was performed before and after BTA treatment. During BTA treatment, a total of 300 IU of BTA was injected cystoscopically into the detrusor muscle, excluding the trigone region. Antibiotic prophylaxis was given. RESULTS: Thirteen of 15 patients (87%) reported that they were fully continent after treatment and the volume of leakage in the two incontinent patients was significantly reduced. Anticholinergic medication was stopped in all patients after BTA treatment. Cystometry showed a marked reduction in pressures after treatment in all patients, with the maximum detrusor pressure during filling being significantly reduced (p < 0.0005) and the maximum volume at a detrusor pressure of <40 cmH2O being significantly increased (p < 0.0005) in all patients. The maximum bladder capacity was increased, although not significantly. The period during which the patients remained continent following treatment ranged from 4 to 12 months (median 7 months). With the exception of slight haematuria, which resolved spontaneously, no side-effects were observed, and no cases of autonomic hyperreflexia were seen during treatment. CONCLUSION: BTA proved to be a highly effective treatment modality for NDO and incontinence in SCL patients. Treatment was easy to perform and the duration of effect was acceptable. Furthermore, BTA treatment was associated with virtually no side-effects.

An unexpected difficult laryngoscopy.

A case of unexpected difficult laryngoscopy in a patient with gross hydrocephalus and generalized hypertonus is described. The 30-month-old girl had no antecedent history of such difficulty, having had two recent uneventful anaesthetics. We suggest that the reason for our inability to open the patient's mouth was a result of contracture of the temporalis muscle. The patient was managed using a laryngeal mask airway with controlled ventilation.

Involuntary detrusor contractions: correlation of urodynamic data to clinical categories.

Data regarding the prevalence and urodynamic characteristics of involuntary detrusor contractions (IDC) in various clinical settings, as well as in neurologically intact vs. neurologically impaired patients, are scarce. The aim of our study was to evaluate whether the urodynamic characteristics of IDC differ in various clinical categories. One hundred eleven consecutive neurologically intact patients and 21 consecutive neurologically impaired patients, referred for evaluation of persistent irritative voiding symptoms, were prospectively enrolled. All patients were presumed by history to have IDC, and underwent detailed clinical and urodynamic evaluation. Based on clinical evaluation, patients were placed into one of four categories according to the main presenting symptoms and the existence of neurological insult: 1) frequency/urgency; 2) urge incontinence; 3) mixed stress incontinence and irritative symptoms; and 4) neurogenic bladder. IDC was defined by detrusor pressure of > or = 15 cm H2O whether or not the patient perceived the contraction; or < 15 cm H2O if perceived by the patient. Eight urodynamic characteristics of IDC were analyzed and compared between the four groups. IDC were observed in all of the neurologically impaired patients, compared with 76% of the neurologically intact patients (P < 0.001). No correlation was found between amplitude of IDC and subjective report of urgency. All clinical categories demonstrated IDC at approximately 80% of cystometric capacity. Eighty-one percent of the neurologically impaired patients, compared with 97% of the neurologically intact patients, were aware of the IDC at the time of urodynamics (P < 0.04). The ability to abort the IDC was significantly higher among continent patients with frequency/urgency (77%) compared with urge incontinent patients (46%) and neurologically impaired patients (38%). In conclusion, when evaluating detrusor overactivity, the characteristics of the IDC are not distinct enough to aid in differential diagnosis. However, the ability to abort IDC and stop incontinent flow may have prognostic implications, especially for the response to behavior modification, biofeedback, and pelvic floor exercise.

Granulocytopenia in Cohen syndrome.

Cohen syndrome is an autosomal recessive disorder characterized by mental retardation, microcephalia and typical craniofacial features, myopia and chorioretinal dystrophy. As some patients were reported to have leucopenia, we collected the haematological data of 26 Finnish Cohen patients. They all had experienced periods of isolated granulocytopenia from an early age. Granulocytopenia was mild to moderate, non-cyclic and never fatal. Most patients suffered from prolonged or repeated gingival or skin infections. We restudied 16 patients. Bone marrow examination revealed in all patients a normo- or hypercellular marrow, with a left-shifted granulopoiesis in 8/16 patients. The response to adrenaline stimulation was subnormal in 12/14 and to hydrocortisone in 8/16 patients, but administration of rhG-CSF caused granulocytosis in the three patients studied. No bone marrow malignancies were seen.

Fisiotpatologia e avaliacao clinica da espasticidade / Physiopathology and clinical evaluation on the spasticity

A espasticidade e definida como uma alteracao motora do tonus muscular caracterizada pela hiper-atividade do reflexo miotatico causada pelo aumento da velocidade de resposta muscular ao estiramento. E extremamente frequente nos casos de lesao do neuronio motor superior da vis cortico-reticulo-bulbo espinal, que altera o sistema inibitorio supra-espinal do reflexo miotatico: lesao da medula espinal, paralisia cerebral, acidentes vasculares, doencas desmielizantes. Nos quadros espasticos encontra-se a hiperatividade dos motoneuronios gama, com exacerbacao da atividade intra-fusal e aumento da resposta do reflexo miotatico. E dependente da extensao e local da lesao nervosa. Este artigo faz uma breve revisao sobre a fisiopatologia e avaliacao clinica da espasticidade.

Lúpus eritematoso sistêmico: atrofia cerebral e manifestaçöes neuropsiquiátricas / Systemic lupus erythematosus: cerebral atrophy and neuropsychiatric manifestations

Os autores relatam o caso de uma paciente de 17 anos de idade, sexo feminino, com poliartrite, febre, insuficiência cardíaca, alteraçäo do comportamento e hipertonia plástica. O diagnóstico de LES foi confirmado laboratorialmente somente através de anticorpos anti-Sm e anti-Ro. Foi realizada tomografia computadorizada cerebral (TCC), que revelou acentuaçäo dos sulcos cerebrais e calcificaçöes periventriculares. A introduçäo de prednisona reverteu o quadro neurpsiquiátrico e uma nova TCC, realizada quatro meses após a primeira, näo demonstrou a referida acentuaçäo dos sulcos cerebrais, mantendo-se apenas as calcificaçöes

Role of constipation and anal hypertonia in the pathogenesis of haemorrhoids.

The hypothesis that haemorrhoids result from chronic constipation was investigated by studying bowel habit, anal pressure profiles and anal compliance in 13 men and 10 women with prolapsing haemorrhoids, 12 women with severe constipation and 14 male and 11 female control subjects. Defaecation was less frequent in women than in men (P less than 0.01) but was independent of the presence of haemorrhoids. Patients with haemorrhoids and control subjects reported similar stool consistency and rarely admitted to straining. Severely constipated women complained of infrequent defaecation, straining at stool and hard motions, but none had prolapsing haemorrhoids. Haemorrhoids were associated with significantly longer anal high-pressure zones and significantly greater maximum resting pressures at all levels of anal distension (P less than 0.01), but minimum residual pressure during rectal distension and maximum squeeze pressure were not significantly different from control subjects. Maximum resting pressure was increased in patients of both sexes with haemorrhoids, but this reached statistical significance only in men (P less than 0.001). Constipated women had normal anal pressure profiles and maximum anal pressures. These data show that patients with haemorrhoids are not necessarily constipated but tend to have abnormal anal pressure profiles and anal compliance. Chronically constipated women do not necessarily have haemorrhoids but have normal anal pressure profiles and compliance. This casts doubt upon the hypothesis that haemorrhoids are caused by constipation.

Hypertonicity of intestinal smooth muscle as a factor of intestinal ischemia in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is thought to be secondary to mucosal ischemia. Because blood flow to the submucosal plexus is derived from vessels traversing three separate layers of visceral smooth muscle (longitudinal, circular, and muscularis mucosa), we investigated whether an increase in their tone might elicit mucosal ischemia. The intestinal intraluminal pressure (IIP) and the superior mesenteric artery (SMA) blood flow were evaluated in 23 dogs before and after either ligation of the SMA or neostigmine infusion into the SMA. Changes in vascularity were assessed by silicone rubber casting, India ink, or arteriography. Ten minutes after ligation of the SMA, there was a considerable increase in peristalsis, IIP, and inability to fill the intestinal microcirculation by the three methods described. Mucosal necrosis was present three hours later. In the neostigmine infusion group after a transient increase in mesenteric flow, the IIP rose 750%, while the mesenteric flow fell by 40%, mucosal necrosis occurred in one hour. When myotomy was performed on the antimesenteric border, mucosal necrosis was prevented. In a third group, neostigmine infused (femoral artery) in the hind limb demonstrated vasodilating effects. The data indicate that an increase in the myogenic tone and frequency of contraction of intestinal smooth muscle can produce mucosal ischemia, thus, intestinal hypertonicity may be an important factor in the pathogenesis of intestinal ischemia and possibly NEC. The effects of neostigmine in these experiments raise questions regarding its use during anesthesia in neonates with intestinal low flow states.