Permanent cutaneous vesicostomy: a pragmatic approach to safely manage lower urinary tract dysfunction in pediatric patients with chronic and life-limiting conditions and neuropathic bladders.

Introduction: Lower urinary tract dysfunction (LUTD) in cerebral palsy (CP) and other neuromuscular diseases can present with chronic retention that leads to hydronephrosis, recurrent urinary tract infections (UTI), and stone formation. Whenever the conservative treatment of LUTD fails for any reason, it is considered to be complicated LUTD, in which a surgical approach is warranted. Cutaneous vesicostomy (CV) is a simple, well-tolerated, and potentially reversible procedure that protects the upper tracts. We describe our experience using CV for this complex population. Materials and methods: Children with CP and other neuromuscular diseases admitted to pediatric long-term care units for palliative care between 2015 and 2019 were included in the study. They present multi-system involvement, polypharmacy, and Gross Motor Function Classification System levels of 4 or 5. We retrospectively studied this population's indications and results of CV. Results: Of the 52 admitted patients, 18 presented LUTD with UTI (n:18; 100%), stones (n:5; 28%), progressive hydroureteronephrosis (n:3; 17%), or stones (n:2; 11%). Conservative initial management (catheterizations, prophylaxis antibiotics) was effective in half the cases. The remaining nine were defined as complicated LUTD and underwent CV. After a mean follow-up of 11.3 months, the follow-up showed improved hydronephrosis in all nine (100%) patients. Recurrent UTIs were no longer seen in eight of nine patients, although three patients required bladder irrigations; bladder stones did not recur after CV; the kidney stones needed further intervention. Revision of the CV was required in two (11%) cases at 12 and 24 months postoperatively due to stoma stenosis. Conclusion: CV is a relatively simple and effective procedure representing a pragmatic solution for managing complicated LUTD in complex long-term institutionalized pediatric palliative care patients with neuropathic bladders.

The effect of underlying diseases on pneumonia risk in patients with neurogenic or tumor-related dysphagia: a retrospective cohort study.

OBJECTIVE: To analyze the association of neurological disorders (ND) and head and neck cancer (HNC) with dysphagia severity and aspiration pneumonia occurrence. METHOD: Retrospective cohort study conducted at a university dysphagia center) for two consecutive years. Patients with ND or HNC were included if they had undergone a flexible endoscopic swallowing evaluation (FEES) at the dysphagia center, and at least one food consistency had been sampled and recorded. Outcomes of interest were swallowing safety, highest penetration-aspiration-score (PASmax), way of food intake, presence of a tracheal tube, and occurrence of pneumonia within the past two years. RESULTS: Of 257 consecutive patients, 199 were enrolled in the study and classified according to their underlying diagnosis into ND (120 patients) or HNC (79 patients). Forty-three HNC patients (54.4%) and 54 ND patients (45%) showed critical dysphagia in FEES (PAS ≥ 6). Binary logistic regression comparing both groups showed patients with ND to be 2.31 times more likely to develop pneumonia. However, if the 32 stroke patients were excluded from the calculation, PASmax remains the only significant variable affecting pneumonia risk in both groups. Liquids were the main challenge for ND patients, while aspirating HNC patients struggled with all consistencies. CONCLUSIONS: The study shows that patients with HNC and ND differ in pneumonia risk only if stroke patients are included in the ND group. If they are excluded, the PAS score is the only remaining risk factor for pneumonia. Thickening liquids may not be suitable for all dysphagic patients; individually tailored measures might be more helpful, especially for HNC patients.

Lower urinary tract dysfunction in the central nervous system neurogenic bladder and the real-life treatment outcome of botulinum toxin A.

Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with central nervous system (CNS) lesions. Cases of cerebrovascular accidents (CVA), Parkinson's disease, dementia, and other intracranial lesions develop poor bladder control with or without urinary difficulty due to loss of cortical perception of bladder filling sensation and poor coordination of urethral sphincter relaxation during reflex micturition. Patients with CNS lesions usually have overactive bladder (OAB) symptoms, including urgency, frequency, incontinence, voiding symptoms of dysuria, large postvoid residual volume, and retention. In elderly patients with severe CNS disease the OAB symptoms are usually difficult to adequately relieve by medical treatment, and thus, their quality of life is greatly. Botulinum toxin A (BoNT-A) is currently licensed and has been applied in patients with idiopathic and neurogenic OAB due to spinal cord injury or multiple sclerosis. However, the application of BoNT-A in the treatment of urinary incontinence due to NLUTD in chronic CNS lesions has not been well-documented. Although cohort studies and case series support BoNT-A treatment for neurogenic OAB, chronic urine retention after intravesical BoNT-A injection for OAB and exacerbated urinary incontinence after urethral BoNT-A injection for voiding dysfunction have greatly limited its application among patients with NLUTD due to CNS lesions. This article reviews the pathophysiology and clinical characteristics of NLUTD in patients with CNS lesions and the clinical effects and adverse events of BoNT-A injection for patients with NLUTD. A flowchart was created to outline the patient selection and treatment strategy for neurogenic OAB.

Morphological Signatures of Neurogenesis and Neuronal Migration in Hypothalamic Vasopressinergic Magnocellular Nuclei of the Adult Rat.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

Urodynamic analysis of the effect of electroacupuncture at different acupoints on the bladder after spinal cord injury.

OBJECTIVE: Guanyuan (CV4), Zhongji (CV3) and Sanyinjiao (SP6) are the most frequently used acupoints for treating neurogenic bladder after spinal cord injury (SCI). However, there has been no investigation to clarify the differences in effects of these acupoints in different types of neurogenic bladder. METHODS: The study was structured with a randomized, two-phase cross over design with a washout period. A routine urodynamic examination was performed first, then, in the order of grouping, electroacupuncture was performed on CV4, CV3, and SP6, respectively，and urodynamic examination was performed to observe the changes of urodynamic indexes in real time. RESULTS: When undergoing electroacupuncture at CV4, CV3, and SP6 in patients with neurogenic detrusor overactivity (DO), the bladder volume at the first occurrence of DO and maximum cystometric capacity increased (p < 0.05), but maximum detrusor pressure (Pdetmax) at DO decreased (p < 0.05), and the changes using CV4 and CV3 was more significantly than using SP6 (p < 0.05). And in patients with in neurogenic detrusor underactivity, there were no significant changes in maximum urinary flow rate and Pdetmax during urination (p > 0.05). CONCLUSION: The immediate relief effect of electroacupuncture at CV4, CV3 on DO was greater than at SP6.

A nomogram for predicting neurogenic lower urinary tract dysfunction in patients with acute ischemic stroke: A retrospective study.

AIMS: To investigate the risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS), and develop an internally validated predictive nomogram. The study aims to offer insights for preventing AIS-NLUTD. METHODS: We conducted a retrospective study on AIS patients in a Shenzhen Hospital from June 2021 to February 2023, categorizing them into non-NLUTD and NLUTD groups. The bivariate analysis identified factors for AIS-NLUTD (p < 0.05), integrated into a least absolute shrinkage and selection operator (LASSO) regression model. Significant variables from LASSO were used in a multivariate logistic regression for the predictive model, resulting in a nomogram. Nomogram performance and clinical utility were evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC). Internal validation used 1000 bootstrap resamplings. RESULTS: A total of 373 participants were included in this study, with an NLUTD incidence rate of 17.7% (66/373). NIHSS score (OR = 1.254), pneumonia (OR = 6.631), GLU (OR = 1.240), HGB (OR = 0.970), and hCRP (OR = 1.021) were used to construct a predictive model for NLUTD in AIS patients. The model exhibited good performance (AUC = 0.899, calibration curve p = 0.953). Internal validation of the model demonstrated strong discrimination and calibration abilities (AUC = 0.898). Results from DCA and CIC curves indicated that the prediction model had high clinical utility. CONCLUSIONS: We developed a predictive model for AIS-NLUTD and created a nomogram with strong predictive capabilities, assisting healthcare professionals in evaluating NLUTD risk among AIS patients and facilitating early intervention.

People with osteoarthritis have a higher component of neuropathic pain as compared to those with rheumatoid arthritis: A cross-sectional study.

Neuropathic pain may be present in a proportion of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Its presence may lead to the requirement of altered management approaches in these conditions. This study investigated the prevalence of neuropathic pain in OA as compared to that in RA. Patients with OA and RA were included cross-sectionally if they had no other known neuropathic disorder. The PainDETECT questionnaire was used to assess neuropathic pain. WOMAC and CDAI scores were used to assess disease severity in OA and RA respectively. 69 patients with OA with a mean WOMAC score of 53.30 ± 16.39 and 98 patients with RA with a mean CDAI of 25.48 ± 16.99 were compared. The median PainDETECT score for OA was 13 (0-30) and RA was 5 (0-37) [p<0.001]. 15 patients with OA and six patients with RA were highly likely to have neuropathic pain, while 15 patients with OA and 30 patients with RA were classified as possibly having neuropathic pain. Thus, the proportion of patients free from neuropathic pain was higher in the RA group (63.3%) than in the OA group (39.1%) [p = 0.003]. Both the prevalence and the severity of neuropathic pain were significantly higher in OA than in RA. These findings suggest that neuropathic pain is an important factor in OA, as in RA, and must be considered in management as well as in future research in both these conditions.

The effect of microvascular decompression of the CN IX-X root entry/exit zone and the ventrolateral medulla in neurogenic hypertension involving the vertebral/basilar artery.

Introduction: Neurogenic hypertension (HTN) is a type of HTN characterized by increased activity of the sympathetic nervous system. Vascular compression is one of the pathogenic mechanisms of neurogenic HTN. Despite Jannetta's solid anatomical and physiological arguments in favor of neurogenic HTN in the 1970's, the treatment for essential HTN by microvascular decompression (MVD) still lacks established selection criteria. Therefore, the subjects selected for our center were limited to patients with primary trigeminal neuralgia (TN) and primary hemifacial spasm (HFS) of the vertebral/basilar artery (VA/BA) responsible vessel type coexisting with neurogenic HTN who underwent MVD of the brainstem to further explore possible indications for MVD in the treatment of neurogenic HTN. Methods: A retrospective analysis of 63 patients who were diagnosed with neurogenic HTN had symptoms of HFS and TN cranial nerve disease. Patients were treated at our neurosurgery department from January 2018 to January 2023. A preoperative magnetic resonance examination of the patients revealed the presence of abnormally located vascular compression in the rostral ventrolateral medulla (RVLM) and the root entry zone (REZ) of the IX and X cranial nerves (CN IX- X). Results: There was no significant difference between the two groups in terms of gender, age, course of HFS, course of TN, course of HTN, degree of HTN, or preoperative blood pressure. Based on the postoperative blood pressure levels, nine out of 63 patients were cured (14.28%), eight cases (12.70%) showed a marked effect, 16 cases (25.40%) were effective, and 30 cases were invalid (47.62%). The overall efficacy was 52.38%. However, 39 cases of combined cranial nerve disease were on the left side of the efficacy rate (66.67%) and 24 cases of combined cranial nerve disease were on the right side of the efficacy rate (29.16%). Discussion: Over the last few decades, many scholars have made pioneering progress in the clinical retrospective study of MVD for neurogenic hypertension, and our study confirms the efficacy of MVD in treating vertebral/basilar artery-type neurogenic hypertension by relieving the vascular pressure of RVLM. In the future, with the development and deepening of pathological mechanisms and clinical observational studies, MVD may become an important treatment for neurogenic hypertension by strictly grasping the surgical indications. Conclusion: MVD is an effective treatment for neurogenic HTN. Indications may include the following: left-sided TN or HFS combined with neurogenic HTN; VA/BA compression in the left RVLM and REZ areas on MRI; and blood pressure in these patients cannot be effectively controlled by drugs.

Results of a defined surgical protocol for treating pediatric neurogenic bladder incontinence in a single institution.

INTRODUCTION: Incontinent pediatric neurogenic bladder (NB) patients face social ostracization and potential renal deterioration. Reconstructive surgery, after maximal medical therapy, requires a difficult decision-making process. Current literature for NB surgeries is difficult to interpret given definitions of dryness, use of augmentation cystoplasty (AC) and the lack of renal preservation. This study assesses the results of a defined surgical protocol to treat incontinent NB patients, using a new composite outcome measure, which includes upper tracts status and a definition of dryness. MATERIALS AND METHODS: This is a retrospective cohort study assessing 33 consecutive incontinent NB patients (Spina bifida 31, Sacral agenesis- 2) who underwent one of 2 procedures between 2008 and 2021. AC with a Mitrofanoff procedure (MP) was performed in patients who had a high detrusor leak point pressure (DLPP) and significant bladder trabeculations (N = 21, Group 1). Children with a low DLPP and non-trabeculated bladders, underwent a modified Young-Dees-Leadbetter/Mitchell procedure with a 360° autologous rectus fascial sling (BOP) with concomitant AC and MP (N-12, Group 2). Post-operative success was defined using a composite grading of success assessing dryness, upper tract stability and medication use. RESULTS: The mean age at surgery was 11.6 years (SD = 6 years), with 21 in Group 1 and 12 in Group 2. Mean follow-up was 3.25 years, with a minimum 24-month follow-up period. Success rate was 90% in Group 1 and 66% in Group 2. No patient had upper tract deterioration following surgery. Redo-surgical intervention, was required in 38% of Group 1 and 50% of Group 2 patients. These include 3 bladder neck injections in Group 1 and 2 bladder neck closure in Group 2, with a final success rate to 95 % in Group 1 and 83 % in Group 2. DISCUSSION: Achieving dryness and preserving upper tracts is a challenge in incontinent NB patients. Dryness rates achieved in this study is comparable, given complications and redo-surgery. Primary bladder neck closure is a radical intervention, but Group 2 patients, may benefit from an upfront discussion of the pros and cons of a bladder neck closure primarily or as a secondary procedure. CONCLUSIONS: Isolated AC obtains acceptable results for a selected subset of incontinent NB patients with significant bladder trabeculation. For those requiring a BOP, the success rate is relatively lower with the higher rate of potential complications and need for redo-surgery.

A retrospective study on the prevalence and risk factors of neurogenic lower urinary tract dysfunction for acute ischemic stroke in China: A case-control study.

PURPOSE: This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. MATERIALS AND METHODS: In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann-Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. RESULTS: Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. CONCLUSIONS: A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

Why are continent catheterizable channels continent? A stomal pressure profilometry feasibility study.

INTRODUCTION: A continent catheterizable channel (CCC) may be a solution for patients with impaired bladder emptying and difficult transurethral access. Leakage of the CCC is a common complication. To prevent leakage, the pressure in the CCC has to be higher than the reservoir (bladder/pouch) pressure in at least one location. It has not been clearly defined through which mechanism(s) the CCC achieves continence. In this feasibility study, we measured the CCC pressure profile in adult patients with various types of CCC's with and without stomal leakage. METHODS: Adult patients with a CCC on a (augmented) bladder or pouch who underwent a urodynamic investigation between January and March 2023 were included. Next to the standard urodynamic investigation, a continuous stomal pressure measurement (CSP) and stomal pressure profilometry with empty bladder (SPP-1) and with filled bladder (SPP-2) of the CCC were performed. RESULTS: A total of 17 patients were included. It was technically possible to perform SPP-1 and SPP-2 in all patients, and to measure the CSP in 16/17 patients. The median maximum stomal pressures in SPP-1 and SPP-2 were 112 (interquartile range [IQR], 76-140) cmH2O and 120 (IQR, 92-140) cmH2O, respectively. Nine patients had stomal leakage during the urodynamic investigation. In five patients, the detrusor leak point pressure (dLPP) was low (<20 cmH2O). A pressure peak at the beginning of SPP-2 was absent in all patients with stomal leakage at low dLPP. CONCLUSION: SPP and CSP measurement in CCCs are feasible. We found differences in SPP-2 between patients with and without leakage at low dLPP, indicative of a role of the intravesical tunnel in continence or high dLPP. The results of this study may improve our understanding of the physiology and dynamics of CCCs as well as the management of CCC-related complications.

A grand mimicker of pulmonary malignancy: The massive mediastinal intercostal nerve tumour.

Mediastinal mass-like manifestations often cause alarm and instigate a myriad of investigative testing to rule out insidious malignant processes. However, a unique and benign finding, the schwannoma can present either incidentally or while in pursuit of a symptomatic presentation. Given its rarity, limited literature exists on these neurogenic tumours with less than three dozen reported cases. No specific guidelines exist regarding the extent of required advanced imaging or degree of invasive evaluation. Therefore, practitioners confronted with these intrathoracic tumours may find management challenging or delayed. We present a case discussing a large benign tumour causing symptomatic burden, the investigative methods implored and treatment modality. We add to the literature another unique presentation of an intercostal nerve sheath tumour with schwannoma pathology.

The supraclavicular approach in the management of cervicothoracic-junction benign neurogenic tumors: A real-world analysis.

Objectives: The study objectives were to evaluate the safety, feasibility, and risk of neurologic complications with the supraclavicular approach in the operative management of cervicothoracic-junction benign neurogenic tumors. Methods: Between January 2012 and April 2023, 115 patients who underwent surgical resection for cervicothoracic-junction benign neurogenic tumors were retrospectively enrolled. Patients were divided into 3 groups based on the surgical approach: supraclavicular alone (Supraclav-Alone), n = 16; Transthoracic-Alone (video-assisted thoracoscopic surgery/Open), n = 87; and supraclavicular combined with transthoracic (Supraclav + video-assisted thoracoscopic surgery/open), n = 12. Clinicopathologic variables and postoperative morbidity including neurologic complications were summarized among the groups. Logistic regression analysis was performed to identify predictors for long-term (>6 months) brachial plexus injuries. Results: The cohort comprised 28 patients (24.3%) who underwent surgical resection using a supraclavicular approach. The Supraclav-Alone group portended the most cephalad location of tumor, the smallest pathologic tumor size, the shortest operative time, the least blood loss, and the least postoperative pain. The incidence of surgical complications, phrenic nerve neuropraxia, recurrent laryngeal nerve neuropraxia, or Horner's syndrome was similar among the groups postoperatively. However, use of the supraclavicular-alone approach (adjusted odds ratio, 0.165; 95% CI, 0.017-0.775) was a predictor for long-term brachial plexus injury complications. Among patients who experienced brachial plexus injury complications, the proportion of patients achieving complete resolution was higher among those undergoing a supraclavicular approach group (Supraclav-Alone: 80.0% vs Supraclav + video-assisted thoracoscopic surgery/Open: 60.0% vs video-assisted thoracoscopic surgery/Open: 25.8%). Conclusions: The supraclavicular approach may be a safe and feasible strategy in the management of cervicothoracic-junction benign neurogenic tumors that does not increase surgical complications and minimizes the severity of brachial plexus injury.

Intermittent Catheterization Continuity Care on Bladder Function Recovery and Quality of Life in Patients After Radical Hysterectomy for Cervical Cancer: A Quasi-Experimental Study.

Background: Bladder dysfunction is a common complication following radical hysterectomy, affecting patients' QOL. Exploring interventions, particularly IC continuity care, is crucial for identifying strategies to enhance postoperative outcomes. This study aimed to assess the impact of continuous intermittent catheterization (IC) care on bladder function recovery and quality of life (QOL) in patients undergoing radical hysterectomy for cervical cancer. Methods: The primary outcome measured was the time to bladder function recovery, with secondary outcomes comprising EORTC QLQ-C30 assessments at 3 and 6 months post-surgery, as well as EORTC QLQ-CX24 evaluations. Meanwhile, urinary complications, readmissions, and outpatient follow-up were also compared. Results: Among the 128 participants, with 64 in each group, indwelling catheterization durations were similar. However, the IC continuity care group exhibited significantly shorter IC duration and bladder recovery time. This group demonstrated superior QOL, lower occurrence rates post-IC, reduced urethral injuries, and higher readmission and outpatient follow-up rates. Conclusion: This study underscores continuous IC care emerges as a beneficial intervention, facilitating accelerated bladder function recovery and improved QOL in patients following radical hysterectomy for cervical cancer.

Longitudinal tracking of hemocyte populations in vivo indicates lineage relationships and supports neural progenitor identity in adult neurogenesis.

Adult neurogenesis, which takes place in both vertebrate and invertebrate species, is the process by which new neurons are born and integrated into existing functional neural circuits, long after embryonic development. Most studies in mammals suggest that self-renewing stem cells are the source of the new neurons, although the extent of self-renewal is a matter of debate. In contrast, research in the crayfish Procambarus clarkii has demonstrated that the neural progenitors producing adult-born neurons are capable of both self-renewing and consuming (non-self-renewing) divisions. However, self-renewing divisions are relatively rare, and therefore the production of adult-born neurons depends heavily on progenitors that are not replenishing themselves. Because the small pool of neural progenitors in the neurogenic niche is never exhausted throughout the long lives of these animals, we hypothesized that there must also be an extrinsic source of these cells. It was subsequently demonstrated that the neural progenitors originate in hemocytes (blood cells) produced by the immune system that travel in the circulation before ultimately integrating into niches where the neural lineage begins. The current study examines the developmental lineage of the three hemocyte types - hyaline (HC), semigranular (SGC) and granular (GC) cells - with the goal of understanding the origins of the progenitor cells that produce adult-born neurons. Longstanding qualitative metrics for hemocyte classification were validated quantitatively. Then, in a longitudinal study, proliferation markers were used to label the hemocytes in vivo, followed by sampling the circulating hemocyte population over the course of two months. Hemolymph samples were taken at intervals to track the frequencies of the different hemocyte types. These data reveal sequential peaks in the relative frequencies of HCs, SGCs and GCs, which were identified using qualitative and quantitative measures. These findings suggest that the three hemocyte types comprise a single cellular lineage that occurs in the circulation, with each type as a sequential progressive stage in hemocyte maturation beginning with HCs and ending with GCs. When combined with previously published data, this timeline provides additional evidence that HCs serve as the primary neural progenitor during adult neurogenesis in P. clarkii.

Determinants of orthostatic hypotension in type 2 diabetes: is cardiac autonomic neuropathy the main factor?

OBJECTIVES: To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of ΔHR/ΔSBP, index of cardiac baroreflex function, in identifying neurogenic OH. METHODS: In 208 participants with T2D, we performed three heart rate based cardiovascular reflex tests (HR-CARTs) and OH test and assessed clinical history and variables. We defined OH as a systolic blood pressure (BP) fall ≥20 and ≥30 mmHg with supine BP <140 and ≥140 mmHg, respectively, and early and confirmed CAN based on 1 and 2 abnormal HR-CARTs. In participants with OH, we measured ΔHR/ΔSBP, using data from the lying to standing and OH test, and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN). RESULTS: OH was present in 25 participants and associated with lower HR-CARTs (P=0.01), higher HbA1c (P=0.0048), presence of CAN (P=0.0058), retinopathy (P=0.037), and peripheral vascular disease (P=0.0056), absence of hypertension (P=0.0008) and physical activity (P=0.0214), but not with interfering drugs and beta-blockers. In a multiple logistic regression, HR-CAN was the main independent determinant of OH (odds ratio: 4.74) with physical activity and hypertension (odds ratio: 0.16 and 0.23) (R2=0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (AUC: 0.816±0.087), and at the cut-off of 0.5 bpm/mmHg a sensitivity of 100% and specificity of 63.2%. CONCLUSION: CAN is still the main determinant of OH in T2D but does not explain all its variance with contribution of comorbidities and physical inactivity. The index ΔHR/ΔSBP might represent a useful clinical tool to identify neurogenic OH.

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction.

DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARß, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-ß was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.

A Prospective Observational Study of Posterior Tibial Nerve Stimulation in Multiple Sclerosis.

INTRODUCTION AND HYPOTHESIS: The objective was to examine the outcomes of posterior tibial nerve stimulation (PTNS) on bladder, bowel, and sexual health-related quality of life among a cohort of patients with multiple sclerosis (MS) with refractory lower urinary tract symptoms (LUTS). METHODS: Patients with MS and refractory LUTS were recruited for a prospective, observational study using PTNS to treat their symptoms. Patients underwent 12 weekly 30-min PTNS sessions and bladder, bowel, and sexual symptoms were evaluated at baseline, 3, 12, and 24 months with voiding diaries, visual analog scales (VAS), and validated patient-reported questionnaires, including the American Urological Association Symptom Score (AUA-SS), Neurogenic Bladder Symptom Score (NBSS), Michigan Incontinence Symptom Index (M-ISI), Health Status Questionnaire, Sexual Satisfaction Scale, and Bowel Control Scale. RESULTS: A total of 23 patients were recruited: 18 started PTNS and 14 completed 3 months of PTNS. Of the 18 who started PTNS, the mean age was 52 years (SD 12), 61% were female, 83% were white, and most patients had relapsing remitting (39%) MS. Baseline (n=18) and 3-month voiding (n=11) outcomes showed no significant change in number of voids or incontinence episodes. The median VAS symptom improvement was 49 (IQR 26.5, 26) and 9 (53%) patients elected for monthly maintenance PTNS. On paired analysis, there was a significant improvement in median change in NBSS, AUA-SS, and M-ISI. There was no significant change in bowel or sexual dysfunction. CONCLUSIONS: This prospective, observational study of PTNS in patients with MS with refractory LUTS shows improvement in patient-reported bladder outcomes, but not in number of voids per day or bowel or bladder function.

Concomitant Botulinum Toxin Injections for Neurogenic Detrusor Overactivity and Spasticity-A Retrospective Analysis of Practice and Safety.

As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.