Neurogenic Detrusor Overactivity In Patients Research Articles

Intravesical oxybutynin treatment for neurogenic detrusor overactivity : Efficacy and safety data from clinical practice with the first intravesical oxybutynin treatment authorized in Germany

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is aneed for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cmH2O ± 26.12 standard deviation (SD) to 21.07 cmH2O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be auseful alternative for patients who do not respond to other therapies or suffered side effects.

Switching from onabotulinum toxin A to abobotulinum toxin A for treating detrusor overactivity in spinal cord injured patient, does it really work?

To assess the efficacy of switching to Abobotulinumtoxin A (ATA) intradetrusor injections (IDI) after failure of Onabotulinumtoxin A (OTA) IDI for the treatment of neurogenic detrusor overactivity in patients with spinal cord injury (SCI). A single-centre retrospective chart review study. All SCI patients who started OTA IDI after 2011 and had an ATA IDI switch were included. The primary outcome was the clinical and urodynamic efficacy of the switch to ATA IIDs at the last follow-up. Secondary outcomes were initial efficacy, duration of ATA treatment, and patient outcome including the occurrence of augmentation enterocystoplasty at last follow-up. Sixty-two patients were included. Eighteen patients (28.9%) were initially responders to ATA IDI. Nine patients (14.5%) remained responders at last follow-up after a median of 17months (AE 8.8-29). Thirty-two patients (51.6%) had had or were awaiting augmentation enterocystoplasty with a follow-up time of 18.5months (IQR 8-27). Eleven patients (17.7%) were on ATA IDI with low efficacy. Seven patients (11.3%) were switched back to OTA and 3patients (4.8%) changed their voiding pattern. Switching from OTA to ATA toxin for IDI in the treatment of detrusor overactivity after spinal cord injury have long-term efficacy for a limited number of patients but may delay the need for surgery.

Efficacy of botulinum toxin in a patient with neurogenic detrusor overactivity

Neurogenic detrusor overactivity is a dangerin terms of the formation of vesicoureteralreflux, pyelonephritis, and chronic kidney disease. The standard treatment for neurogenic detrusor overactivity is intermittent catheterization of the bladder in combination with M-cholinoblockers, which is not always sufficient. In the article, the authors briefly outlined the physiological basis of intradetrusor injections of botulinum toxin in neurogenic detrusor overactivity in patients with myelodysplasia who underwent surgery for spinal hernias, tumors of the spinal canal, as well as patients with spinal trauma. The technology of intradetrusor injections of botulinum toxin is shown, possible complications are described. The effectiveness of intradetrusor injections of botulinum toxin is shown by a specific clinical example — a description of the medical history of a child who has a history of surgical treatment for a spinal hernia in the newborn period. After the operation, neurogenic detrusor overactivity was revealed, insensitive to treatment with M-cholinoblockers. Complications were vesicoureteral reflux and recurrent pyelonephritis. The results of cystometry before and after double administration of botulinum toxin are shown. Detrusor hypertension was stopped, pyelonephritis remission was achieved, trabecularity of the bladder mucosa was stopped. Simultaneously with the introduction of botulinum toxin, endoscopic correction of vesicoureteral reflux was performed.

Long-term results of augmentation ileocystoplasty in spinal cord injury patients.

IntroductionThe aim of this article was to report the long-term results of increased ileocystoplasty in 58 patients with spinal cord injury (SCI) with an impact on overall renal function and quality of life. In a representative number of patients, where we followed individual subjects for more than 20 years, we wanted to determine their quality of life and preservation of renal function after surgery.Material and methodsAfter unsuccessful conservative therapy of urinary incontinence, increased ileocystoplasty was performed. In addition to biochemical analysis, intravenous urography (IVU) was performed preoperatively (urography and/or ultrasound assessment of the upper urinary tract) and urodynamic tests were performed in all patients preoperatively.ResultsAfter a follow-up of patients within the group (>20 years), 2 patients reported being incontinent. The median elapsed time of action was 20 (13–24) years. Vesical capacity increased in all cases postoperatively when the median vesical capacity was 420.0 (387.5–460.0) ml (p <0.001). Long-term complications included use of bladder chambers, kidney stones and urosepsis. Creatinine clearance confirmed satisfactory renal function after the elapsed time period from surgery.ConclusionsThe results confirmed that augmentation ileocystoplasty had excellent long-term outcomes in the definitive therapy of refractory neurogenic detrusor overactivity in patients with SCI.

The Botulinum Treatment of Neurogenic Detrusor Overactivity: The Double-Face of the Neurotoxin.

Botulinum neurotoxin (BoNT) can counteract the highly frequent involuntary muscle contractions and the uncontrolled micturition events that characterize the neurogenic detrusor overactivity (NDO) due to supra-sacral spinal cord lesions. The ability of the toxin to block the neurotransmitter vesicular release causes the reduction of contractions and improves the compliance of the muscle and the bladder filling. BoNT is the second-choice treatment for NDO once the anti-muscarinic drugs have lost their effects. However, the toxin shows a time-dependent efficacy reduction up to a complete loss of activity. The cellular mechanisms responsible for BoNT effects exhaustion are not yet completely defined. Similarly, also the sites of its action are still under identification. A growing amount of data suggest that BoNT, beyond the effects on the efferent terminals, would act on the sensory system recently described in the bladder mucosa. The specimens from NDO patients no longer responding to BoNT treatment displayed a significant increase of the afferent terminals, likely excitatory, and signs of a chronic neurogenic inflammation in the mucosa. In summary, beyond the undoubted benefits in ameliorating the NDO symptomatology, BoNT treatment might bring to alterations in the bladder sensory system able to shorten its own effectiveness.

A Korean Postmarketing Study Assessing the Effectiveness of OnabotulinumtoxinA for the Treatment of Neurogenic Detrusor Overactivity or Idiopathic Overactive Bladder Using a Validated Patient-Reported Outcome Measure.

PurposeOnabotulinumtoxinA has demonstrated efficacy and safety in the treatment of urinary incontinence (UI) associated with neurogenic detrusor overactivity (NDO) and idiopathic overactive bladder (OAB); however, real-world evidence is limited. This postmarketing surveillance study aimed to assess the effectiveness and safety of onabotulinumtoxinA in Korean patients with UI associated with NDO or OAB with an inadequate response or intolerance to anticholinergics.MethodsPatients received 200 U (NDO) or 100 U (OAB) of onabotulinumtoxinA. Effectiveness (assessed using the validated International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]) and safety were assessed for 1–4 months after onabotulinumtoxinA administration.ResultsOverall, 686 patients (NDO, 161; OAB, 525) comprised the safety population; of these, 612 patients were analyzed for effectiveness. There was a significant decrease (P<0.0001) in the mean (standard deviation) ICIQ-SF scores in the NDO (–6.8±5.5) and OAB (–6.0±6.4) groups after onabotulinumtoxinA administration. A decrease of >5 points from baseline in the ICIQ-SF score was observed in 64.9% and 47.3% of patients in the NDO and OAB groups, respectively. Following treatment, 59.9% in the NDO group and 43.0% in the OAB group were dry. There was no effect of age on effectiveness in either group. Only 10 adverse drug reactions (ADRs) were reported in 5.6% of NDO patients and 20 ADRs in 3.2% of OAB patients. Most ADRs in both groups were related to the lower urinary tract such as dysuria (NDO, 1.2%; OAB, 0.6%) and urinary retention (NDO, 0.6%; OAB, 1.5%).ConclusionsEffectiveness and safety of onabotulinumtoxinA in Korea in a real-world setting was demonstrated.

Long-term discontinuations of botulinum toxin A intradetrusor injections for neurogenic detrusor overactivity: a multicenter study

PurposeData on long-term outcomes of intradetrusor injections of botulinum toxin A (BTX-A) for neurogenic detrusor overactivity (NDO) are lacking. The aim of the present manuscript was to assess the outcomes of intradetrusor injections of BTX-A for NDO after more than 10 years of follow-up. MethodsA retrospective chart review of all consecutive neurological patients who had received either onabotulinumtoxin A or abobotulinumtoxin A intradetrusor injections for NDO between January 2002 and November 2007 at three academic centers, was performed. The primary outcome measure was 10 years discontinuation rate. Other outcomes of interest were: failure, reasons for discontinuation and subsequent treatments of NDO. Discontinuation-free and failure-free survivals were estimated using Kaplan-Meier analyzes. Results140 patients were included in the study. Ten-year discontinuation-free survival and failure-free survival rates were 49.1% and 73% respectively. The most common reason for discontinuation was failure (43.7%; primary and secondary in 17.2% and 26.5% of cases respectively). Secondary failure occurred after a median number of 8 injections and a median time of 80.1 months from the first injection. Other reasons for discontinuation were: patient’s decision (28.1%), non BTX-A related improvement of urinary incontinence (14.1%), progression of the neurological condition (12.5%) and adverse event (1.6%). Discontinuation-free survival was significantly poorer in spina bifida patients compared to patients with multiple sclerosis or spinal cord injury (p= 0.02). ConclusionsOver a half of NDO patients discontinue intradetrusor BTX-A within the first 10 years after the first injection. Spina Bifida patients are at high risk of discontinuation.

PD36-06 THE EFFICACY OF ONABOTULINUMTOXIN A IN PATIENTS WITH PARKINSON′S DISEASE AND NEUROGENIC DETRUSOR OVERACTIVITY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II1 Apr 2018PD36-06 THE EFFICACY OF ONABOTULINUMTOXIN A IN PATIENTS WITH PARKINSON′S DISEASE AND NEUROGENIC DETRUSOR OVERACTIVITY Ranjan Arianayagam, Lewis Chan, and Vincent Tse Ranjan ArianayagamRanjan Arianayagam More articles by this author , Lewis ChanLewis Chan More articles by this author , and Vincent TseVincent Tse More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1729AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with Parkinson′s Disease (PD) and extrapyramidal syndromes often report voiding dysfunction and overactive bladder symptoms. Onabotulinum Toxin A (BTXA) injections has proven efficacy in the treatment of neurogenic overactive bladder. We report the efficacy of intravesical BTXA injections for treatment of drug refractory detrusor overactivity in patients with PD. METHODS A retrospective review of patients with drug refractory overactive bladder who underwent BTXA (Botox) at Concord Hospital from 2007 to 2017 was conducted. All patients underwent multichannel urodynamic assessment. Urodynamic findings were reviewed and clinical outcomes obtained from medical records. RESULTS 12 patients (mean age 75) had PD and 1 patient had supranuclear palsy. 2 patients had high pressure detrusor overactivity (DO) on urodynamics, 4 patients had decreased compliance and the remainder had low amplitude DO. 2 patients had raised post void residuals on urodynamics and the remainder had a normal voiding phase with no bladder outlet obstruction.10 patients had an initial 100 unit Botox injection; 3 patients (including 2 with high pressure DO), had 200 units initially, and 5 patients had dose escalation from an initial 100 units. 6 patients (46%) had significant improvement in their storage symptoms after BTXA and 3 patients (23%) reported mild improvement. Only 1 of 5 patients had an improvement with dose escalation. Overall, 9 of 13 patients (69%) reported an improvement in their symptoms. The majority of patients had some ongoing storage symptoms despite Botox and only 2 (15%) regained total continence.Post-operatively, 4 patients (31%) had elevated post void residuals, 3 of whom had a normal voiding phase on urodynamics. Of these, 2 required temporary clean intermittent self catheterization and one required a long term SPC. This is significantly higher than the 2% rate of retention post BTXA for patients with non-neurogenic overactive bladder at our institution and may represent impaired voiding function in the context of progressive neurodegenerative disease. CONCLUSIONS Whilst the majority of patients with drug refractory neurogenic overactive bladder related to PD reported some symptom improvement following BTXA, only 50% had good response. One third of patients had elevated residuals. Our study shows lower efficacy of BTXA therapy and a higher retention rate in PD patients and illustrates the difficulty in the management of neurogenic detrusor overactivity in patients with progressive neurodegenerative disease. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e728 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ranjan Arianayagam More articles by this author Lewis Chan More articles by this author Vincent Tse More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D‐network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)‐modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, αSMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Influence of bladder lithiasis on lower urinary tract dynamics in patients with spinal cord injury.

A prospective and a case-matched control study. To study the lower urinary tract dysfunction associated with bladder lithiasis in patients with spinal cord injury (SCI). Toledo (Spain). We have carried out a urodynamic study in 30 patients with SCI with lithiasis in their bladder before and 3 months after bladder endoscopic lithotripsy. This second study was compared with the urodynamic findings of a different group of 30 patients with SCI, without a history of bladder lithiasis, paired with cases by gender and date of urodynamic study. We have found that the prevalence of neurogenic detrusor overactivity (NDO) was significantly different after bladder lithotripsy, although the cystomanometric capacity was significantly increased. A group of patients with lithiasis showed a maximum flow rate, a voiding maximum detrusor pressure and the detrusor contractility parameter Wmax lower than that in controls. On the other hand, a voiding abdominal straining was found to be significantly greater than that in controls. Bladder lithiasis affects the presence of NDO in patients with SCI. Patients with SCI who develop bladder lithiasis present a lower detrusor contractility power compared with those who do not.

166 - Combined treatment of DDAVP and mirabegron represents an effective treatment of neurogenic detrusor overactivity in patients with multiple sclerosis

166 - Combined treatment of DDAVP and mirabegron represents an effective treatment of neurogenic detrusor overactivity in patients with multiple sclerosis

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to supra-sacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor) three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modeling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types by using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, SMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Neurogenic detrusor overactivity in patients with hereditary spastic paraplegias

Hereditary spastic paraplegia (HSP) represents a clinically and genetically heterogeneous group of neurodegenerative diseases, with a worldwide estimated prevalence of 1.3/100,000 [1] . The “pure” form of HSP is a characterized by a progressive spastic paraplegia, often associated with lower urinary tract symptoms (LUTS) (72.4% to 77.6%) [2] , [3] . However, urologic complications are rarely reported. The aim of this study was to characterize clinical and urodynamic aspects of LUTS following HSP, and to describe treatment and urological complications of LUTS in a large series of HSP patients. We performed a monocentric retrospective evaluation based on review of medical records of HSP patients admitted in the department of PRM from 1999 to 2016. Inclusion criteria were patients > 18 years. Presenting HSP. Clinical, urodynamic and radiologic data were recorded. Statistical analysis was performed using Microsoft Excel software. Thirty-three HSP patients were included. Mean age was 62 ± 14 years with 70% of men. The mean follow-up was 8.10 ± 5 years. Patients presented LUTS: urgency (85%), hesitancy (85%), nocturia (56%) and urinary incontinence (54%). The post-void residual volume (PVR) was over 100 mL in 70%. NDO was diagnosed according to urodynamic testing in 83% of patients, associated in 76% of them with a detrusor-sphinctger-dyssinergia (DSD). HSP patients were exposed to urologic–nephrologic complications: febrile urinary tract infections (25%), urolithiasis (21%), hydronephrosis (8%) and renal failure (17%). HSP patients have been mainly treated with anticholinergics (69%) and 10% were switched to intradetrusor botulinum toxin. Clean intermittent catheterization was performed by 30% of patients. Three patients underwent a non-continent surgical urinary diversion. A significant percentage of HSP patients presenting LUTS mainly resulting of the association of PVR, DO and DSD. However, for the first time, uro-nephrologic complications following LUTS related to HSP are underlined. Thus, HSP patients should be assessed, such as SCI patients, in order to improve management and HSP patients’ quality of life with a decrease of uro-nephrologic complications.

Effects of onabotulinumtoxinA on cardiac function following intradetrusor injections

OnabotulinumtoxinA intradetrusor injections are considered a highly effective localized therapy for refractory detrusor overactivity. However, despite evidence for distant systemic effects of onabotulinumtoxinA, little is known on potential systemic side effects following intradetrusor injections. Given that onabotulinumtoxinA is a highly potent toxin this is an important safety issue specifically with regard to repeat injections and parallel treatments with botulinum toxin. Hence, it was the purpose of this prospective study to investigate, using heart rate variability (HRV) analysis, whether onabotulinumtoxinA causes systemic effects on cardiac function following intradetrusor injections.Patients with neurogenic detrusor overactivity (NDO) and age-matched healthy controls were recruited. Concomitant medication and diseases affecting the cardio-vascular system were exclusion criteria. A 3-channel resting electrocardiogram (ECG) was recorded in supine position for 15min during four consecutive visits: 1) 2weeks prior onabotulinumtoxinA intradetrusor injections, 2) 10min prior injections, 3) 30min after injections, and 4) 6weeks after injections. NDO patients received intradetrusor injections (300units Botox®) between visits 2 and 3. The control group had no intervention.Short-term (5min) HRV analysis included assessment of frequency and time domain parameters. Statistical analysis was performed using ANOVA with repeated measures and the t-test. Due to multiple comparisons, α was corrected to 0.0125 (Bonferroni method).Twelve healthy volunteers (5♀, 7♂; 46±12years old) and 12 NDO patients (5♀, 7♂; 46±13years old) completed all measurements. Comparing both groups, resting heart rate was significantly higher in the patients group at visit 4 only. No further significant differences in time and frequency domain parameters were discovered.Within the NDO group, standard deviation of the normal to normal intervals (SDNN) in the ECG demonstrated a significant decrease (1.70 to 1.53ms, p=0.003) from visit 3 to 4, whereas the total power (TP) significantly increased (3.05 to 3.29ms2, p=0.009) from visit 2 to 3. This increase subsided until visit 4.Study limitations: single treatment investigation under resting conditions only.In conclusion, onabotulinumtoxinA intradetrusor injections do not seem to affect resting state cardiac function. Short-term changes such as total power might rather result from natural cardio-vascular responses to the procedure itself (e.g. discomfort, stress). Further detailed investigations also under physical stress and repeated injections are necessary to fully exclude systemic cardiac side effects of onabotulinumtoxinA intradetrusor injections.

Intradetrusor injections of onabotulinum toxin A (Botox®) 300 U or 200 U versus abobotulinum toxin A (Dysport®) 750 U in the management of neurogenic detrusor overactivity: A case control study.

To compare the outcomes of the first intradetrusor injections of abobotulinum toxin 750 U and onabotulinum toxin 200 and 300 U in patients with neurogenic detrusor overactivity (NDO). A retrospective case-control study was conducted including 211 NDO patients treated in three consecutives eras with onabotulinum toxin 300 U (2004-2006; 80 patients), abobotulinum toxin 750 U (2007-2011; 78 patients) or onabotulinum toxin 200 U (2011-2014; 53 patients). Urodynamic and clinical parameters were compared between groups. The primary endpoint was the rates of success defined as the combination of urgency, urinary incontinence, and detrusor overactivity resolution. When comparing abobotulinum toxin to onabotulinum toxin any doses (200 or 300 U; n = 133), success rates were similar (65.4% vs. 55.6%; P = 0.16). Patients treated with abobotulinum toxin 750 U had higher success rate (65.4% vs. 41.5%; P = 0.007) compared to those who received onabotulinum toxin 200 U. In contrast, there were similar success rates in abobotulinum toxin 750 U and onabotulinum toxin 300 U groups (65.4% vs. 65%; P = 0.91) but with a trend towards longer interval between the first and the second injection in the onabotulinum toxin 300 U group (12.4 vs. 9.3 months; P = 0.09). Intradetrusor injections of abobotulinum toxin 750 U for NDO provided better outcomes than injections of onabotulinum toxin 200 U. Success rates of abobotulinum toxin 750 U and onabotulinum toxin 300 U were similar but interval between injections tended to be longer with onabotulinum toxin 300 U. Neurourol. Urodynam. 36:734-739, 2017. © 2016 Wiley Periodicals, Inc.

Botulinum Toxin to Treat Neurogenic Bladder.

Alteration in neural control from suprapontine areas to the nerves innervating the bladder can lead to bladder dysfunction and the development of a neurogenic bladder (NGB). Patients with NGB often suffer from urinary incontinence, which can lead to adverse events such as urinary tract infections and decubiti, in addition to creating a large care burden for family members or healthcare providers and significantly impairing patient quality of life. The common failure of anticholinergic medications has spurned the development of second-line treatments, including the use of botulinum toxin. OnabotulinumtoxinA (onaBoNT-A; BOTOX, Allergan, Inc.) was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat neurogenic detrusor overactivity in patients with urinary incontinence resulting from a NGB. In this review the authors summarize pertinent results from key trials leading to FDA approval of onaBoNT-A as well as more recent long-term data.

The role of botulinum toxin A in treating neurogenic bladder.

Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox®, Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport®, Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future.

Efficacy and safety of two administration modes of an intra‐detrusor injection of 750 units dysport® (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo‐controlled phase IIa study

Assess the efficacy and safety of abobotulinumtoxinA (Dysport®) in adult patients with neurogenic detrusor overactivity (NDO). This Phase IIa, international, multicentre, double-blind, randomised, placebo controlled, pilot study enrolled 47 patients with NDO and urinary incontinence resulting from spinal cord injury (SCI) or multiple sclerosis (MS). Patients were treated with 15 intra-detrusor injections of Dysport 750 U or the equivalent placebo (n = 16 and 7) or 30 injections of Dysport 750 U or the equivalent placebo (n = 17 and 7). Primary endpoint was change from baseline in mean number of daily incontinence episode frequency (IEF) at day 84. Secondary endpoints included change from baseline in urodynamic parameters and quality of life (QOL). A safety assessment was also conducted. Adjusted mean changes from baseline in IEF were -3.2 (-76%) and -1.7 (-15%) for 15 injections Dysport and placebo groups, respectively, (P = 0.1103) and -3.2 (-88%) and -2.6 (-73%) for 30 injections Dysport and placebo groups, respectively, (P = 0.0686). Statistically significant improvements in maximum cystometric capacity, maximum detrusor pressure and volume at first contraction were reported in the Dysport groups compared with placebo (P < 0.05). Improvements in QOL were reported. Three muscle weakness episodes were reported as serious adverse events in two tetraplegic and one paraplegic patient, all in the 15 injections Dysport group. Both 15 and 30 injections administration modes of Dysport decreased daily IEF and resulted in significant improvements in urodynamic parameters in NDO patients with MS or SCI. Reduction to 15 injection sites did not appear to be associated with any impact on efficacy. Neurourol. Urodynam. 36:457-462, 2017. © 2016 Wiley Periodicals, Inc.

Re: The Clinical and Urodynamic Results of Percutaneous Posterior Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Patients with Parkinson’s Disease

Re: The Clinical and Urodynamic Results of Percutaneous Posterior Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Patients with Parkinson’s Disease

The Clinical and Urodynamic Results of Percutaneous Posterior Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Patients With Parkinson's Disease

To investigate the effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment after 12 weeks on urodynamic and clinical findings in patients with Parkinson's disease (PD) with neurogenic detrusor overactivity. A total of 47 patients with PD with neurogenic detrusor overactivity were enrolled in the study. Urodynamic studies before and after 12-week PTNS treatment were performed. International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Overactive Bladder Questionnaire (OAB-V8), and Overactive Bladder Questionnaire Short Form (OAB-q SF) have been assessed before and after PTNS treatment. The mean first involuntary detrusor contraction volume (1st IDCV) on standard cystometry was 133.2 ± 48.1 (24-265) mL, whereas it was 237.3 ± 43.1 (145-390) mL after PTNS. The mean maximum cystometric capacity (MCC) on standard cystometry was 202.2 ± 36.5 (115-320) mL, whereas it was 292.1 ± 50.6 (195-395) mL after stimulation. The improvements in the first involuntary detrusor contraction volume and maximum cystometric capacity were statistically significant after stimulation. The mean Pdetmax at first involuntary detrusor contraction, maximal detrusor pressure at maximum cystometric capacity, PdetQmax, Qmax, and post-void residual volume were statistically significant after 12-week stimulation. Mean parametric improvements at 12-week PTNS treatment from baseline included daytime frequency decreased by 5.6 voids daily, urge incontinence decreased by 3.1 episodes daily, urgency episodes decreased by 6.3 episodes daily, nocturia decreased by 2.7 voids, and voided volume improved by a mean of 92.6 mL. The change from baseline on the ICIQ-SF, OABv8, and OAB-q at 12-week PTNS treatment demonstrated statistically significant improvements. These results have demonstrated that PTNS improves the lower urinary tract symptoms and urodynamic parameters in patients with PD.