Risk factors for upper urinary tract deterioration in adult patients with spina bifida.

PURPOSE: Neurogenic bladder associated with spina bifida disease remains a major cause for mortality or morbidity due to kidney damages. However, we currently do not know which urodynamic findings are associated with an higher risk of upper tract damages in spina bifida patients. The objective of the present study was to evaluate urodynamic findings associated with functional kidney failure and/or with morphological kidney damages. METHODS: A large single-center restrospective study was conducted in our national referral center for spina bifida patients using our patients' files. All urodynamics curves were assessed by the same examinator. Functional and/or morphological evaluation of the upper urinary tract were done at the same moment as the urodynamic exam (between 1 week before and 1 month after). Kidney function was assessed using creatinine serum levels or 24 h urinary creatinine levels (creatinine clearance) for walking patients, or with the 24 h urinary creatinine level for wheelchair-users. RESULTS: We included 262 spina bifida patients in this study. Fifty-five patients had a poor bladder compliance (21.4%) and 88 of them had detrusor overactivity (33.6%). Twenty patients had a stage 2 kidney failure (eGFR < 60 ml/min) and 81 patients out of 254 (30.9%) had an abnormal morphological examination. There were three urodynamic findings significantly associated with UUTD: bladder compliance (OR = 0.18; p = 0.007), Pdetmax (OR = 14.7; p = 0.003) and detrusor overactivity (OR = 1.84; p = 0.03). CONCLUSION: In this large series of spina bifida patients, maximum detrusor pressure and bladder compliance are the main urodynamic findings determinants of UUTD risk.

Transanal irrigation is a better choice for bowel dysfunction in adults with Spina bifida: A randomised controlled trial.

AIM: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients. METHODS: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis. RESULTS: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10. CONCLUSIONS: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.

Long-term outcomes of artificial urinary sphincter in female patients with spina bifida.

AIMS: To report the long-term functional outcomes of artificial urinary sphincter (AUS) implantation in female patients with spinal dysraphism and stress urinary incontinence (SUI) related to intrinsic sphincter deficiency (ISD). METHODS: The charts of all spina bifida female patients with SUI due to ISD who underwent AUS (AMS 800) implantation between 2005 and 2019 at three academic departments of urology were retrospectively reviewed. Reoperation was defined as either revision or explantation of the AUS device. Reoperation-free survival of the AUS device was estimated using the Kaplan-Meier method. Continence status as per patients' subjective assessment was categorized as follows: complete continence (no pads), improved continence, unchanged SUI or worsened SUI. RESULTS: Twenty-three patients were included, 69.6% were self-catheterizing. The median follow-up was 14 years. Median time to first reoperation was 10 years. Survival rates without reoperation were 85.9%, 41.8%, 34.6%, and 20.9% at 5, 10, 15, 20 years, respectively. Survival rates without AUS explantation were 90.7%, 66.3%, 55.2%, and 41.4% at 5, 10, 15, 20 years, respectively. None of the patients who underwent device explantation had a new AUS implanted. The only predictive factor of reoperation-free survival was the type of spinal dysraphism (hazards ratio = 3.60 for closed vs. open dysraphism; p = .04). At last follow-up, 17 of the 23 patients were fully continent (73.9%). CONCLUSION: AUS in female patients with spina bifida may be associated with satisfactory long-term functional outcomes and a high reoperation rate. The median time to first reoperation was similar to what is reported in the male AUS literature (10 years).

Risk of prolapse and urinary complications in adult spina bifida patients with neurogenic acontractile detrusor using clean intermittent catheterization versus Valsalva voiding.

AIMS: To assess the relative risks of pelvic organ prolapse (POP) and urinary complications in adult spina bifida patients with neurogenic acontractile detrusor voiding with Valsalva versus those using clean-intermittent catheterization (CIC). METHODS: We conducted a retrospective analysis including all spina bifida patients with neurogenic acontractile detrusor with a minimum follow-up of 12 months. Patients were then divided in two groups according to their bladder management: voiding with Valsalva versus CIC. The primary endpoint was any de novo or worsened rectal and/or pelvic organ prolapse (POP) diagnosed during follow-up. The secondary outcome was urinary complications defined as febrile urinary tract infections (UTI) and/or urolithiasis and/or renal failure. RESULTS: Fifty-five patients (50.9% were males) met the inclusion/exclusion criteria: 28 voiding with Valsalva and 27 performing CIC. At baseline, the rates of vaginal prolapse (44.4% vs 50%; P = 0.99), and rectal prolapse/intussusception (25.9% vs 21.4%; P = 0.76) were similar in both groups. After a median follow-up of 80.6 and 65.6 months, respectively (P = 0.29), the rate of de novo or worsened rectal prolapse/intussusception was higher in the Valsalva voiding group than in the CIC group (32.1% vs 3.7%; P = 0.01). De novo or worsened vaginal prolapses were also more common in the Valsalva voiding group, but it did not reach statistical significance (33.3% vs 11.1%; P = 0.29). CONCLUSIONS: Valsalva voiding might be harmful in adult spina bifida patients with neurogenic acontractile detrusor as it may increase the risk of rectal prolapse/intussusception. Overall, the prevalence of POP and rectal prolapse was high in both groups.

Defecation disorders in Spina Bifida: Realistic goals and best therapeutic approaches.

AIMS: Spina Bifida (SB) is a rare congenital condition that frequently impairs the neurological control of both fecal continence and defecation. Several therapeutic strategies have been proposed but impact assessment is lacking. Our objectives were to quantify the symptomatic improvement and to determine the optimal strategy in this rare condition where randomized controlled trials are difficult to conduct. METHODS: Data were extracted from a prospective database. The present analysis focused on patients having undergone at least two gastroenterological assessments. A standardized therapeutic approach was used from the first visit. Improvement was quantified by the variation of quantified symptomatic scores. RESULTS: The data of of 57 adults with SB (gender F/M: 30/27 [52.6/47.4%]; mean age: 33.8 [18.5] years) were extracted. After a mean follow-up of 46 months, 23/57 patients (40.4%) had at least improvement of one point of the Cleveland Clinic Incontinence score (CCIS); 13/57 (22.8%) reported a significant improvement of continence (delta score >50%). Five of the twelve patients (41.6%) with CCIS < 5 at baseline became incontinent over time. The neurological level was not associated with a worse continence outcome. Work on stool consistency and transanal irrigation were the most useful strategies in those with significant improvement of continence. CONCLUSIONS: Using conventional strategies, a benefit on fecal continence occurs in only one out of five patients suffering from Spina Bifida and continent patients at baseline can develop fecal incontinence over time. A strategy targeting improved control of defecation (transanal irrigation) and a standardization of follow-up protocol might be beneficial.

Urinary TIMP-2 and MMP-2 are significantly associated with poor bladder compliance in adult patients with spina bifida.

AIMS: To assess the predictive values of six urinary markers (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], matrix metalloproteinase 2 [MMP-2], tissue inhibitor metalloproteinase 2 [TIMP-2], transformation growth factor ß-1 [TGF-B1], and prostaglandin 2 [PGE2]) for adverse urodynamic features and for upper urinary tract damage in adult patients with spina bifida. MATERIALS AND METHODS: A single-center prospective trial was conducted from March 2015 to March 2017 including all consecutive adult patients with spina bifida seen for urodynamic testing. The urine was collected and stored at -80°C. A urodynamic and an upper urinary tract were systematically performed. At the end of the inclusion period, urines were defrosted and urinary nerve growth factor, BDNF, TIMP-2, and TGF-B1 were assessed using validated ELISA kits. The urinary markers levels were adjusted on the urinary creatinine level. Urinary MMP-2 levels were assessed by zymography. RESULTS: Fourty patients were included. Only TIMP-2 and MMP-2 were significantly associated with poor bladder compliance (P = .043 and P = .039, respectively). TIMP-2 was also the only urinary marker significantly associated with upper urinary tract damage on imaging (OR = 19.81; P = .02). Of all urodynamic parameters, bladder compliance and maximum detrusor pressure were the only ones associated with upper urinary tract damage on imaging (P = .01 and P = .02), The diagnostic performances of urinary TIMP-2 for upper urinary tract damage were slightly superior to PdetMax and bladder compliance with an area under the curve of 0.72. CONCLUSION: Urinary TIMP-2 and MMP-2 were significantly associated with poor bladder compliance and urinary TIMP-2 was significantly associated with upper urinary tract damage. These findings support a pathophysiological role of extracellular matrix remodeling in poor bladder compliance of adult patients with spina bifida.

Artificial Urinary Sphincter in Male Patients with Spina Bifida: Comparison of Perioperative and Functional Outcomes between Bulbar Urethra and Bladder Neck Cuff Placement.

PURPOSE: We evaluated the perioperative and long-term functional outcomes of bladder neck and peribulbar cuff placement of an artificial urinary sphincter in a population of adult male patients with spinal dysraphism. MATERIALS AND METHODS: We retrospectively analyzed the French spina bifida network database. Patients who underwent implantation of an artificial urinary sphincter from January 1985 to November 2015 were selected and stratified into 2 groups according to cuff location, that is bladder neck vs bulbar urethra. Explantation-free and revision-free device survival was estimated by the Kaplan-Meier method and compared with the log rank test. Cox regression models were created to assess prognostic factors of artificial urinary sphincter device failure. RESULTS: A total of 65 patients were included in study. Most patients were not wheelchair bound. The cuff was implanted around the bulbar urethra at 46 procedures (59%) and around the bladder neck in 32 (41%). In the peribulbar and bladder neck groups median revision-free device survival was 11.7 and 14.3 years, respectively (p = 0.73). Median explantation-free device survival was 18.5 and 24.5 years, respectively (p = 0.08). On multivariate analysis clean intermittent catheterization was the only predictor of artificial urinary sphincter device failure. Cuff location had no influence. At the last followup satisfactory continence was similar in the 2 groups (83% vs 75%, p = 0.75). CONCLUSIONS: In male patients with spinal dysraphism morbidity and functional outcomes were similar for bladder neck and bulbar urethra cuff placement but with a trend toward longer survival without explantation in the bladder neck group. Clean intermittent catheterization was the only predictor of shorter device survival on multivariate analysis.

Comparison of neurogenic lower urinary tract dysfunctions in open versus closed spinal dysraphism: A prospective cross-sectional study of 318 patients.

AIMS: To compare the neurogenic lower urinary tract dysfunction (NLUTD) in patients with closed spinal dysraphism (CSD) versus patients with open spinal dysraphism (OSD) as well as their management patterns. METHODS: A prospective cross-sectional study was conducted between September 2007 and December 2015 including all spina bifida patients seen at the multidisciplinary French national referral center for spina bifida. NLUTD and its management were compared between the OSD and CSD groups. RESULTS: Three hundred and eighteen patients were included for analysis: 100 with a CSD (31.5%) and 218 with an OSD (68.6%). The prevalence of urinary incontinence did not differ significantly between the two groups (43% vs 52.8%; P = 0.11), the mean Qualiveen score was also similar (2.7 vs 2.5, P = 0.22). The voiding mechanism was clean intermittent catheterization, spontaneous voiding, suprapubic tube, and ileal conduit in 55% versus 44%; 29.8% versus 47%; 2.8% versus 3% and 11.9% versus 6% of OSD and CSD patients, respectively (P = 0.02). There were comparable prevalences of detrusor overactivity (36.5% vs 38.8%; P = 0.68) and impaired bladder compliance (34.9% vs 31.7%; P = 0.56) in both groups. Augmentation cystoplasty was more common in patients with OSD (32.1% vs 11%; P < 0.0001). CONCLUSIONS: In this prospective cohort, NLUTD were more common in OSD with a higher rate of patients requiring a surgical treatment and a lower rate of patients with preserved spontaneous voiding. However, when present, NLUTD was as severe and troublesome in patients with closed versus open spinal dysraphism.

Folic acid supplementation use during the peri-conceptional period among professionals of a hospital in France.

Folic acid insufficiency is an important risk factor for congenital neural tube defects. Despite recommendations and national campaigns, the proportion of women taking folic acid in the peri-conceptional period remains insufficient worldwide. We describe in this study the proportion of peri-conceptional folic acid supplementation use and its determinants among a population of hospital workers during the course of a prevention campaign. We performed a single-center cross sectional study in a university hospital in France. Data were collected during 2 months in 2019 by an online questionnaire sent to all professionals. We collected information about folic acid supplementation use, its modalities (form, period, frequency and dosage) and reason for initiating or not supplementation. Response rate was 11.4 % (n = 1,075/9,447). Among the 748 women who reported at least one pregnancy, 72.7 % (95 % CI: 69.4-76.0 %) reported taking folic acid during their last pregnancy. Main reason for initiating supplementation was information given by a health professional (87.8 %), especially by gynaecologists-obstetricians. Principal factors associated with folic acid supplementation use were age between 25 and 35 years, high level of education and recent pregnancy. Folic acid supplementation use is still not systematic before and during pregnancy, even among health professionals. There is a case for mandatory folic acid fortification for the French general population.

Urologic Disorders are Still the Leading Cause of In-hospital Death in Patients With Spina Bifida.

OBJECTIVE: To assess and analyze the contemporary causes of in-hospital deaths of spina bifida patients. METHODS: It was a cross-sectional observational study of the longitudinal national cohort of all patients hospitalized in French public and private hospitals. We analyzed the data from the French hospital discharge database (Programme de Médicalisation des Systemes d'Information, PMSI) from 2009 to 2014. The number of in-hospital deaths was extracted using the combination of the ICD-10 codes "Q05" or "Q760" and a discharge code = 9. RESULTS: There were 138 in-hospital deaths of spina bifida patients over the 6-year study period. The median age at death was 41 years (IQR: 25-52). The median age at death was significantly lower in patients with vs without hydrocephalus (26.6 vs 45.5 years; P <.0001). The leading cause of in-hospital death was urologic disorders (n = 24; 17.3%). Other main causes of death were pulmonary disorders (n = 23; 16.7%), neurologic disorders (n = 19; 13.8%), and bowel disorders (n = 15; 10.9%). Upper urinary tract damage accounted for most of the urologic causes of death: 8 patients died from urinary tract infections (33.3%), 7 patients died from renal failure (29.2%), 4 died from bladder cancer (16.7%), and 5 from other urologic causes. The only variable significantly associated with a death from urologic causes was the absence of hydrocephalus (OR = 0.26; P = .009). CONCLUSION: Urologic disorders remain the leading cause of in-hospital death in spina bifida patients in France. The present study highlights that efforts to improve the urologic management of the spina bifida population are still greatly needed.

Contrast-enhanced CT Texture Parameters as Predictive Markers of High-risk Urodynamic Features in Adult Patients with Spina Bifida.

OBJECTIVE: To investigate computed tomography (CT) texture analysis of the bladder wall as a predictor of urodynamics findings in adult patient with spina bifida. METHODS: A single-center prospective trial was conducted from March 2015 to March 2017 including all consecutive adult spina bifida patients seen for urodynamic testing. A contrast-enhanced abdominal CT was systematically performed in all patients during the same visit. Texture features of the bladder wall related to the gray-level histogram and gray-level co-occurrence were evaluated on CT images. Multivariate analysis was performed to identify independent predictors of poor bladder compliance and detrusor overactivity among clinical and texture parameters. RESULTS: Fourty patients were included. The Lasso penalized logistic regression analysis identified 2 texture parameters as potential predictors of poor bladder compliance: Skewness (coefficient weight, -1.81) and S.1.1.SumVarnc (coefficient weight, -3.52). Multivariate logistic regression analysis confirmed skewness (odds ratio [confidence interval 95%] = 0.40 [0.14, 0.97], P = .04) as an independent predictor of poor bladder compliance. The Lasso penalized logistic regression analysis identified one texture parameters as potential predictor of detrusor overactivity: Kurtosis (coefficient weight, -3.52), which was confirmed in multivariate logistic regression analysis (odds ratio [confidence interval 95%] = 1.12 [1.01, 1.55], P = .02). CONCLUSION: Our findings demonstrate that CT texture analysis of the bladder wall might be an interesting tool to identify spina bifida patients with high risk urodynamic features.