Magnetic resonance image connectivity analysis provides evidence of central nervous system mode of action for parasacral transcutaneous electro neural stimulation - A pilot study.

INTRODUCTION: Parasacral transcutaneous electriconeural stimulation (pTENS) is a common treatment modality for patients with overactive bladder (OAB). Its mechanism of effectiveness has yet to be elucidated. Recent studies with fMRI in adults with implanted sacral nerve stimulators impute its effectiveness on changes in the brain involving the anterior cingulate cortex (ACC) and prefrontal cortex (PFC). AIM: The study set out to evaluate brain connectivity utilizing functional MRI to the outline the mechanism of action of pTENS in the brain. METHODS: Ten adult volunteers without urinary tract symptoms underwent fMRI. Electrodes were placed on the skin at sacral level (S2) (Experimental Stimulation - pTENS) and on the right scapular region (Sham Stimulation - sTENS). Stimulation was done twice on each site for 6 min at a frequency of 10 Hz and pulse width of 260 µs and intensity determined by the motor threshold. A 6 min resting state fMRI was also done twice as control. Functional connectivity data was acquired during each state (resting, pTENS and sTENS). Standard functional connectivity preprocessing was performed. Seed connectivity was examined to investigate changes in ACC functional connectivity between the stimulations and resting-state conditions. Significance was assessed at p < 0.05 corrected for multiple comparisons. RESULTS: For all conditions (pTENS, sTENS, and rest), standard patterns of ACC connectivity were detectable with strong connectivity between the ACC and subcortical regions and between the ACC and the frontal lobe. Functional connectivity between ACC seed and the dorsal lateral prefrontal cortex (DLPFC) was significantly increased during pTENS compared to rest. sTENS did not increase connectivity between the ACC seed and DLPFC when compared to rest. DISCUSSION: Preliminary results indicate that ACC is a major site of activation during pTENS. Increased connectivity between ACC and DLPFC may be a possible mechanism of pTENS effectiveness, which appears to be specific to pTENS compared to sTENS. This study is limited to the small size at this time which prevents further investigation at other sites in the brain. CONCLUSIONS: The study confirms our original aim which was to define if parasacral TENS actually has a central effect.

Evaluation and treatment of nonmonosymptomatic nocturnal enuresis: a standardization document from the International Children's Continence Society.

PURPOSE: This document represents the consensus guidelines recommended by the ICCS on how to evaluate and treat children with nonmonosymptomatic nocturnal enuresis (NMNE). The document is intended to be clinically useful in primary, secondary and tertiary care. MATERIALS AND METHODS: Discussions were held by the board of the ICCS and a committee was appointed to draft this document. The document was then made available to the members of the society on the web site. The comments were vetted and amendments were made as necessary to the document. RESULTS: The main scope of the document is the treatment of NMNE with drugs other than desmopressin-based therapy. Guidelines on the assessment, and nonpharmacologic and pharmacologic management of children with NMNE are presented. CONCLUSIONS: The text should be regarded as an expert statement, not a formal systematic review of evidence-based medicine. It so happens that the evidence behind much of what we do in the care of enuretic children is quite weak. We do, however, intend to present what evidence there is, and to give preference to this rather than to experience-based medicine, whenever possible.

Atorvastatin ameliorates tubulointerstitial fibrosis and protects renal function in chronic partial ureteral obstruction cases.

PURPOSE: Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model. MATERIALS AND METHODS: All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of alpha-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day. RESULTS: At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in alpha-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin. CONCLUSIONS: This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function.

Pediatric overactive bladder syndrome: pathophysiology and management.

Detrusor overactivity, also known as the overactive bladder syndrome (OAB), urge syndrome, hyperactive bladder syndrome, persistent infantile bladder, and detrusor hypertonia, is the most common voiding dysfunction in children. Until recently, the concepts that had been used to dictate the management of this problem in children were based on the foundation that this was a primary bladder problem and or a delay in maturation in the nervous system of children. The expectation that children would outgrow their problems led many pediatric urologists and other practitioners to tell the parents of these children 'that they would not be wetting themselves on their wedding day.' However, it has become apparent from recent studies in adult patients with voiding dysfunctions that they had symptoms present as children. Recent findings of associations between lower urinary tract symptoms and sexual dysfunction and between voiding dysfunctions and neuropsychiatric problems have opened up a new frontier into the possible mechanisms of OAB in children that would explain these problems, link them together, and explain the continued problems that adult patients face. These findings point to OAB as a symptom of a more centrally located dysfunction that affects multiple systems. The objective of this review was to evaluate the neuroanatomy and neurophysiology of voiding and neuropharmacologic effects. We considered not only the available research and clinical data within the urologic field but also outside the field so that these data could be combined to generate a unified theory that could possibly explain many of the associated symptoms that are commonly found in pediatric OAB. Treatment modalities that are currently available for managing OAB were also explored. Currently available data indicate that pediatric OAB and many pediatric voiding dysfunctions may be part of a more generalized problem that affects multiple systems: notably bowels, bladder, sexual and ejaculatory function, control of blood pressure, and even mood and behavior. We explain the relationship that the bowel has with pediatric OAB and also the link that other neuropsychiatric problems have with OAB. This article describes which drug may be best suited to treat OAB in children and what treatment modalities are available when first-line drugs fail. In conclusion, the movement away from a vesicocentric way of thinking to a more corticocentric mode of thinking along with new imaging modalities that can examine the brain as it works will be of great value in determining future treatments of OAB. Medications generated from these evidence-based studies will hopefully treat the underlying disease process and not just the symptoms.

Overactive bladder in children. Part 2: Management.

PURPOSE: The management of pediatric overactive bladder syndrome has relied primarily on anticholinergics and a bowel regimen. In many cases the results have been ineffective and they have frustrated many parents, patients and practitioners. We explored other treatment modalities that may be more effective than the regimens that we currently use. A thorough understanding of the causes of overactive bladder syndrome are essential to help us find the appropriate treatment for individuals. MATERIALS AND METHODS: We looked at numerous treatment modalities that are being used for overactive bladder syndrome and matched them to a specific cause of overactive bladder syndrome that would be best suited to treat the problem. The treatment of constipation as a mainstay for pediatric overactive bladder syndrome was explored as well as its different options. New treatment modalities involving electrical stimulation were explored as well as botulinum A toxin injections. RESULTS: The effectiveness of each treatment was assessed, thereby providing the reader with a foundation for choosing the appropriate treatment. CONCLUSIONS: The treatment of pediatric overactive bladder syndrome is not as simple as placing children on anticholinergics and, if there is no response, simply saying that they will outgrow it. The causes of overactive bladder syndrome are multifactorial and a better understanding of the pathophysiology will allow us to target treatments appropriately for individuals.

Dysfunctional elimination syndrome as an etiology of idiopathic urethritis in childhood.

PURPOSE: Idiopathic urethritis (IU) of childhood or urethrorrhagia is a common problem characterized by blood spotting in the underwear between voiding. A clear etiology has not been established and treatments vary. We postulate that idiopathic urethritis is a manifestation of underlying dysfunctional elimination syndrome (DES). MATERIALS AND METHODS: During a 5-year period we reviewed the records of all children diagnosed with IU in our practice. In total 72 children fit the analysis criteria. There were 68 boys and 4 girls. All children presented with either gross blood per urethra or microhematuria. Children with active infection, immunodeficiency, neurogenic bladder, vesicoureteral reflux, infravesical obstruction, urethral trauma or other genitourinary anomalies were excluded. Evaluation included thorough history and physical examination, urinalysis and urine culture. Renal and bladder ultrasound, voiding cystourethrogram and uroflow/electromyogram/post-void residual volume were obtained in select patients. Study children were divided into 2 cohorts. The first cohort (group 1, 37 patients) was treated with traditional remedies using antibiotics, urinary analgesics and/or anticholinergics. The second cohort (group 2, 35 patients) was treated by bowel and bladder regimens, laxatives when necessary, and biofeedback and/or alpha-blockers when sphincter dyssynergia was identified. RESULTS: A total of 13 patients in group 1 (35%) had a full response to treatment, 6 (16%) had a partial response and 18 (49%) failed to respond. A total of 29 patients in group 2 (83%) had a full response to treatment, 2 (6%) had a partial response and 4 (11%) had no response. It took an average of 12.1 months to respond fully in group 1, while in group 2 the same full response took an average of 5.2 months. Of the 18 children who crossed over from group 1 to group 2, 15 (83%) had a full response with an average response time of 7.3 months. CONCLUSIONS: Our data clearly reveal a higher cure rate when children with urethritis are treated according to DES guidelines. IU of childhood is a manifestation of underlying DES and should be treated as such.

Chylous ascites following surgical treatment for wilms tumor.

PURPOSE: Postoperative chylous ascites is a rare complication of retroperitoneal surgery that has considerable morbidity. We review the pathogenesis and management of chylous ascites following surgical treatment of Wilms tumor. MATERIALS AND METHODS: We identified 9 children with chylous ascites after surgical treatment of Wilms tumor. Of these cases 3 were treated at a single institution during the last 20 years and 6 were identified during retrospective chart reviews of patients enrolled in National Wilms Tumor Studies 3 and 4 to identify surgical complications. Chylous ascites presented as increased abdominal girth and poor feeding. Paracentesis or laparotomy was diagnostic. RESULTS: Patient age at presentation with Wilms tumor ranged from 6 to 95 months (median 15). Left nephrectomy was performed in 5 cases, right nephrectomy in 3, and left nephrectomy and partial right nephrectomy in 1 with bilateral disease. Lymphadenectomy including the hilar and periaortic lymph nodes was performed in 5 patients, 4 of whom also underwent some form of suprahilar lymph node dissection. Three patients underwent lymph node sampling of the hilar, periaortic and some suprahilar lymph nodes. All children received adjuvant chemotherapy and 4 were treated with adjuvant irradiation to the surgical bed before the diagnosis of chylous ascites. The interval between surgery and diagnosis of ascites ranged from 12 to 49 days (median 21). Of the patients 7 were successfully treated with conservative measures, total parenteral nutrition and/or a diet containing primarily medium chain triglycerides, and 2 required invasive procedures, including exploratory laparotomy and ligation of disrupted lymphatic vessels or placement of a peritoneovenous shunt. CONCLUSIONS: Extensive lymph node dissection, particularly above the level of the renal hilum, appears to be associated with the development of postoperative chylous ascites. The National Wilms Tumor Study guidelines do not require formal lymph node dissection for staging and only lymph node sampling is recommended. Elimination of formal lymphadenectomy along with meticulous ligation of lymphatics should decrease the incidence of this complication. Fortunately, conservative treatment with total parenteral nutrition and/or medium chain triglycerides will remedy the problem in the majority of children.

Biofeedback therapy expedites the resolution of reflux in older children.

PURPOSE: In older children the spontaneous resolution rate of low grade vesicoureteral reflux is low and currently its management is controversial in regard to surgery versus prophylaxis versus observation alone. Bladder dysfunction in children with neurogenic bladders and to a less declarative degree in neurologically intact children has a role in the etiology or persistence of reflux. We determine the impact of biofeedback therapy on neurologically intact children with vesicoureteral reflux and detrusor-sphincter dyssynergia. MATERIALS AND METHODS: Vesicoureteral reflux was detected by voiding cystourethrography in children evaluated for urinary tract infections. Children with breakthrough infections or dysfunctional voiding based on history underwent uroflowmetry with concomitant patch electromyography of the external sphincter. Dyssynergia was defined as increased or steady electromyography activity during micturition. Biofeedback was initially performed weekly and the interval increased as indicated. The goals were to eliminate dyssynergia and reduce or eliminate post-void residual urine. Voiding cystourethrography was performed 1 year later to determine the status of the reflux. Ureteral reimplantation was performed during the period of biofeedback when indicated. RESULTS: From February 1997 to March 2001, 25 children 6 to 10 years old (mean age 9) with vesicoureteral reflux and detrusor-sphincter dyssynergia were treated with biofeedback therapy. There were 31 units (5 bilateral) with reflux, which was grade I in 10, II in 15, III in 5 and IV in 1. Children underwent an average of 7 sessions of biofeedback (range 2 to 20). On followup voiding cystourethrography, vesicoureteral reflux resolved in 17 units (55%), grade improved in 5 (16%) and reflux remained unchanged in 9 (29%). All cured vesicoureteral reflux was grade I (8 cases) or II (9). Four children (5 renal units) underwent reimplantation. In cured children there were no breakthrough infections during or since therapy and post-void residual urine decreased from an average of 40% before to 10% after therapy. Symptoms of urgency, daytime wetting and hoarding of urine improved or were eliminated in all children with resolved vesicoureteral reflux. CONCLUSIONS: Treating external detrusor-sphincter dyssynergia in older children with low grade vesicoureteral reflux, with biofeedback results in 1-year resolution rates that are considerably greater than historical resolution rates. External detrusor-sphincter dyssynergia should be screened for in children when surgery or discontinuation of chemoprophylaxis is considered so that biofeedback can be started.